







































All articles are permanently available online to the public without restrictions or subscription fees. They are free to be used, cited, 

and distributed, provided that appropriate acknowledgment is included. Authors retain the copyright of their original contributions 

and grant the Canadian Online Publication Group (COPG) a license to publish the article and identify itself as the original 

publisher. CPOJ articles are licensed under the Creative Commons Attribution 4.0 International License. 

 

CPOJ Website: https://jps.library.utoronto.ca/index.php/cpoj/index 

Editorial Office: cpoj@online-publication.com    

ISSN: 2561-987X 

CPOJ is a member of, and subscribes to the principles of, the Committee on Publication Ethics (COPE).   

 

 

VOLUME 7, ISSUE 2 

 2024 
 

REVIEW ARTICLE 

Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 2 - A scoping review of physical biomarkers. 

Canadian Prosthetics & Orthotics Journal. 2024; Volume 7, Issue 2, No.3. https://doi.org/10.33137/cpoj.v7i2.43716 

 

https://jps.library.utoronto.ca/index.php/cpoj/index
mailto:cpoj@online-publication.com
https://publicationethics.org/about/our-organisation
https://publicationethics.org/members/canadian-prosthetics-orthotics-journal
https://doi.org/10.33137/cpoj.v7i2.43716


 

1 

Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 2 - A scoping review of physical biomarkers. 
Canadian Prosthetics & Orthotics Journal. 2024; Volume 7, Issue 2, No.3. https://doi.org/10.33137/cpoj.v7i2.43716 

 

 

REVIEW ARTICLE 

 

WOUND MANAGEMENT, HEALING, AND EARLY PROSTHETIC REHABILITATION: PART 2 - 

A SCOPING REVIEW OF PHYSICAL BIOMARKERS 

Williams-Reid H1, Johannesson A2, Buis A1*  

1 Department of Biomedical Engineering, Faculty of Engineering, University of Strathclyde, Glasgow, Scotland. 
2 Össur Clinics EMEA, Stockholm, Sweden.   

 
  
 

 

 

 

  

 

 

 

 

 

 

 

 

 

 

 

INTRODUCTION   

 

1: OVERALL RATIONALE, AIMS, AND OBJECTIVES 

Wound healing is the biological process of tissue repair 

following damage,1 such as amputation surgery or 

prosthetic-use induced deep tissue injuries (DTIs). The 

process  comprises  four  interrelated  stages:  hemostasis,  

 

 

 

inflammation, proliferation, and tissue remodeling.2-4 It 

demands a high degree of cellular coordination, introducing 

several avenues through which impairments can occur. 

Consequently, wound healing can be stalled (also referred 

to as non-healing, impaired, or chronic) not by one isolated 

factor, but by several smaller contributing issues.5 Common 

post-amputation surgical site healing complications include 

infection, pain, hematomas, tissue necrosis, poor residual 

limb formation, recurrent ulceration, wound dehiscence, and 

stitch abscesses.6,7 Persistent complications, in other 

words, poor healing, can necessitate revision surgeries or 

even re-amputation at more proximal levels.6  

Despite the complexity of wound healing, current healing 

assessments remain largely surface-level and subjective. 

This is especially relevant for major lower limb amputees, 

 
OPEN  ACCESS 

ABSTRACT 

BACKGROUND: The timely provision of load-bearing prostheses significantly reduces healthcare costs and 

lowers post-amputation mortality risk. However, current methods for assessing residuum health remain 

subjective, underscoring the need for standardized, evidence-based approaches incorporating physical 

biomarkers to evaluate residual limb healing and determine readiness for prosthetic rehabilitation. 

OBJECTIVE(S): This review aimed to identify predictive, diagnostic, and indicative physical biomarkers of 

healing of the tissues and structures found in the residual limbs of adults with amputation. 

METHODOLOGY: A scoping review was conducted following Joanna Briggs Institute (JBI) and PRISMA-

ScR guidance. Searches using “biomarkers”, “wound healing”, and “amputation” were performed on May 6, 

2023, on Web of Science, Ovid MEDLINE, Ovid Embase, Scopus, Cochrane, PubMed, and CINAHL 

databases. Inclusion criteria were: 1) References to physical biomarkers and healing; 2) Residuum tissue 

healing; 3) Clear methodology with ethical approval; 4) Published from 2017 onwards. Articles were assessed 

for quality (QualSyst tool) and evidence level (JBI system), and categorized by study, wound, and model 

type. Physical biomarkers that were repeated not just within categories, but across more than one of the 

study categories were reported on. 

FINDINGS: The search strategy identified 3,306 sources, 157 of which met the inclusion criteria. Histology 

was the most frequently repeated physical biomarker used in 64 sources, offering crucial diagnostic insights 

into cellular healing processes. Additional repeated indicative and predictive physical biomarkers, including 

ankle-brachial index, oxygenation measures, perfusion, and blood pulse and pressure measurements, were 

reported in 25, 19, 13, and 12 sources, respectively, providing valuable data on tissue oxygenation and 

vascular health. 

CONCLUSION: Ultimately, adopting a multifaceted approach that integrates a diverse array of physical 

biomarkers (accounting for physiological factors and comorbidities known to influence healing) may 

substantially enhance our understanding of the healing process and inform the development of effective 

rehabilitation strategies for individuals undergoing amputation. 

 

 

 

ARTICLE INFO 

Received: July 5, 2024 

Accepted: November 29, 2024 

Published: December 5, 2024 
 

CITATION 

Williams-Reid H, Johannesson A, 

Buis A. Wound management, 

healing, and early prosthetic 

rehabilitation: Part 2 - A scoping 

review of physical biomarkers. 

Canadian Prosthetics & Orthotics 

Journal. 2024; Volume 7, Issue 2, 

No.3. 

https://doi.org/10.33137/cpoj.v7i2

.43716 

KEYWORDS 

Amputation, Scoping Review, 

Wound Healing, Surgical Site 

Healing, Physical Biomarkers, 

Physical Markers of Healing, 

Residuum Healing, Residual Limb 

Healing, Wound Management, 

Early Prosthetic Rehabilitation 

Please refer to the end of the 

article for a list of Abbreviations 

& Acronyms. 

 

* CORRESPONDING AUTHOR: 

Professor Arjan Buis, PhD 

Department of Biomedical Engineering, Faculty of Engineering, University 
of Strathclyde, Glasgow, Scotland. 

E-Mail: arjan.buis@strath.ac.uk 

ORCID ID: https://orcid.org/0000-0003-3947-293X 

 

Journal Homepage: https://jps.library.utoronto.ca/index.php/cpoj/index 

Volume 7, Issue 2, Article No.3. 2024 

 

 

https://doi.org/10.33137/cpoj.v7i2.43716
https://doi.org/10.33137/cpoj.v7i2.43716
https://doi.org/10.33137/cpoj.v7i2.43716
mailto:arjan.buis@strath.ac.uk
https://orcid.org/0000-0003-3947-293X
https://jps.library.utoronto.ca/index.php/cpoj/index


 

2 

Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 2 - A scoping review of physical biomarkers. 
Canadian Prosthetics & Orthotics Journal. 2024; Volume 7, Issue 2, No.3. https://doi.org/10.33137/cpoj.v7i2.43716 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X WOUND MANAGEMENT: PHYSICAL BIOMARKERS 

Williams-Reid et al., 2024 

who typically receive a customized prosthetic limb within 3 

to 20 weeks post-surgery, depending on wound healing.8,9 

Prosthetic fitting significantly improves mobility, physical 

health, and quality of life,9-11 yet determining residual limb 

readiness remains subjective and inconsistent.12  

Clinical judgment, based on superficial wound 

assessments, varies widely, and there are no standardized 

guidelines for evaluating readiness.12-14 Factors such as 

wound healing, pain management, and limb volume are 

considered, but specific measurable indicators are lacking. 

Recent studies highlight debates around key clinical 

decisions, such as whether to use rigid or soft dressings in 

the immediate post-operative stage to promote healing.15,16 

Moreover, individuals awaiting amputation frequently 

present with multiple comorbidities that complicate the 

healing process. A leading cause of amputation is diabetes-

related complications,17 yet hyperglycemia can lead to 

vascular stiffening, microvascular dysfunction, reduced 

tissue oxygenation, and, consequently, impaired wound 

healing.18 

This variability in clinical practices underscores the need for 

more objective measures, such as biomarkers, to assess 

wound healing and readiness for prosthetic use. 

Biomarkers, defined by the U.S. FDA (Food & Drug 

Administration) as measurable indicators of biological 

processes or responses to treatment,19 offer a way to 

reduce the subjectivity inherent in current practices. 

However, there is limited research on using biomarkers to 

monitor healing and support early prosthetic rehabilitation 

post-amputation. Existing studies, like those investigating 

tissue composition changes during prosthetic use,20 focus 

on mature residual limbs, while early-stage limbs face 

higher risks of issues like ulceration and volume fluctuation, 

complicating socket fit.21 Exploring these early stages is 

crucial for successful prosthetic rehabilitation and 

preventing further surgeries. To meet this research need, a 

scoping review was developed and implemented with the 

following aim: 

Identify predictive, diagnostic, and/or indicative biomarkers 

(physical, chemical, or other) of healing of the tissues and 

structures found in the residual limbs of adults with 

amputation. 

To meet this aim, the following objectives were compiled: 

1)  Collate and synthesize the reported definitions of healing 

and non-healing in the literature investigating healing of the 

tissues and structures found in the residual limbs of adults 

with amputation. 

2) Identify and collate physical biomarkers predictive, 

diagnostic, and/or indicative of healing repeated in sources 

investigating healing of the tissues and structures found in 

the residual limbs of adults with amputation.  

3) Identify and collate chemical biomarkers predictive, 

diagnostic, and/or indicative of healing repeated in sources 

investigating healing of the tissues and structures found in 

the residual limbs of adults with amputation. 

4) Assess the quality and levels of evidence of sources 

investigating healing of the tissues and structures found in 

the residual limbs of adults with amputation.   

The term "physical" refers to biomarkers like wound pH, 

temperature, or collagen levels detected through 

histochemical staining,22 while "chemical" pertains to 

markers present in wound tissue, fluids, serum/blood, 

sebum, saliva, or sweat, such as cytokines or matrix 

metalloproteinases. Indicative biomarkers suggest the 

presence of a condition or physiological state but are not 

definitive. Predictive biomarkers provide prognostic 

information, indicating the likelihood of developing a 

condition or predicting a patient's response to treatment. 

Diagnostic biomarkers confirm the presence of a specific 

disease or condition, or in this context, definitively identify 

the progression of healing. 

2: PART 2 - RATIONALE, AIMS, AND OBJECTIVES 

This article (Part 2) addresses objective 2 and constitutes 

the second instalment in a series of three articles, each of 

which sequentially examines objectives 1 to 3. As 

concluded in Part 1,23 there exists a significant lack of 

consensus and standardization in defining healing and non-

healing within the literature that investigates the healing of 

the tissues and structures found in the residual limbs of 

adults with amputations. Most approaches fail to consider 

deeper tissue healing and the mechanical properties of the 

tissue essential for functionality, particularly in the context 

of prosthetic use.23 To address this, Part 1 outlined steps for 

developing a tailored and relevant scale that incorporates 

biomarkers for assessing wound healing in the context of 

residual limbs post-amputation.  

Physical biomarkers assess the macro-level physiological 

properties of a biological system, such as heart rate, which 

indicates cardiac functionality. These biomarkers are 

typically measured in real-time or continuously, offering the 

potential for ongoing monitoring of wound healing. For 

instance, recent work by Patel et al.24 synthesized research 

on wearable electronics for skin wound monitoring and 

healing, noting the development of sensors capable of real-

time monitoring of physical biomarkers, including pH, 

temperature, moisture, and oxygen. Day et al.12 similarly 

concluded that future research should assess 

transcutaneous oxygen perfusion, along with other non-

invasive measures of blood flow and perfusion, as a more 

objective means of tracking the progression of healing over 

time. Notably, transcutaneous oxygen pressure (TcPO2) 

was the only objective measure employed among the 15 

sources reviewed in their study.12 Previous research has 

indicated that a TcPO2 value below 40 mmHg is associated 

https://doi.org/10.33137/cpoj.v7i2.43716


 

3 

Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 2 - A scoping review of physical biomarkers. 
Canadian Prosthetics & Orthotics Journal. 2024; Volume 7, Issue 2, No.3. https://doi.org/10.33137/cpoj.v7i2.43716 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X WOUND MANAGEMENT: PHYSICAL BIOMARKERS 

Williams-Reid et al., 2024 

with a 24% increased risk of healing complications in lower 

limb amputations compared to values above 40 mmHg.25 

Physical biomarkers are already widely utilized in various 

healthcare settings for different applications. For example, 

peripheral oxygen saturation (SpO2) has been employed by 

the UK National Health Service (NHS) to detect early 

deterioration in patients with COVID-19 in primary and 

community care settings.26 Medically certified pulse 

oximetry fingertip devices were distributed to patients, 

enabling the rapid real-time measurement of oxygen 

saturation levels without the need for blood samples.26 

Furthermore, SpO2 has also been shown to correlate with 

wound healing; Park et al.27 demonstrated that, during the 

early stages of wound healing, oxygen saturation can drop 

to a maximum of 85%, indicating a hypoxic wound 

environment. As healing progresses, oxygen saturation 

typically increases and is maintained within the normal 

range of 95% to 100% by the end of the healing process, as 

observed in a rat cutaneous wound model.27 These existing 

pulse oximetry systems demonstrate significant potential for 

adaptation and reapplication in the monitoring of residual 

limb healing and early prosthetic rehabilitation. This serves 

as a clear example of how the requirement to identify and 

develop techniques for quantifying biomarkers within the 

proposed healing assessment scale can be effectively 

addressed. 

In conclusion, physical biomarkers represent promising 

objective measures for inclusion in the development of an 

assessment scale of residual limb healing post-amputation. 

Therefore, the aim of this review was to: 

Identify predictive, diagnostic, and/or indicative physical 

biomarkers of healing in the tissues and structures found in 

the residual limbs of adults with amputations. 

To achieve this aim, the following objectives have been 

established: 

1) Identify and compile physical biomarkers that are 

predictive, diagnostic, and/or indicative of healing as 

reported in sources investigating the tissues and structures 

of residual limbs in adults with amputations. 

2)  Identify and summarize the techniques used to quantify 

these physical biomarkers in studies focused on the healing 

of tissues and structures in residual limbs of adults with 

amputations. 

3)  Assess the quality and levels of evidence in sources 

investigating the healing of tissues and structures found in 

the residual limbs of adults with amputations. 

METHODOLOGY 

Given the novelty of the research question and the broad 

array of sources available on biomarkers, a scoping review 

was deemed the most appropriate approach to address the 

research question. The complete review methodology has 

been previously detailed in Part 1.23 In brief, the review 

adhered to the Preferred Reporting Items for Systematic 

Reviews extension for Scoping Reviews (PRISMA-ScR) 

checklist and guidance28,29 and followed the Joanna Briggs 

Institute (JBI) guidelines.30-33 Data management was 

conducted using Excel Version 2303 (Microsoft, 

Washington, USA) operating on Windows 11 Version 22H2 

(Microsoft, Washington, USA). 

1: INCLUSION CRITERIA AND SEARCH STRATEGY 

The first screening phase, focusing on titles and abstracts, 

applied primary inclusion criteria including references to 

biomarkers of wound healing, healing of tissues found in the 

residual limb, and publications from 2017 onwards. Due to 

the limited research specifically addressing biomarkers for 

residual limb healing, the inclusion criteria were expanded 

to encompass literature on biomarkers of healing, requiring 

that participants have a clearly defined wound in tissues and 

structures comparable to those of an amputation residuum. 

In the second phase of full-text screening, additional criteria 

were introduced, including clear and reproducible 

methodologies, ethical approval (where applicable), and the 

involvement of human participants (aged 18+) or murine 

models. To ensure a comprehensive review, sources were 

considered from diverse contexts, such as home, hospital 

community, and academic institutions, and across multiple 

disciplines, including healthcare professionals and 

engineers. Additionally, to mitigate bias towards high-

income countries and Western publication bias,34,35 studies 

from any geographical region were included, provided they 

were available in the English language due to the primary 

reviewer’s language limitations.  

An exhaustive list of terms derived from the research 

question was generated and the search strategy was 

piloted. Finalized search terms, based on terms 

“biomarker”, “amputation”, and “wound healing”, were then 

applied to several databases, including Web of Science, 

MEDLINE (hosted on the Ovid platform), Embase (hosted 

on the Ovid platform), Scopus, Cochrane, PubMed, and 

CINHAHL. The extensive number of sources generated 

during the initial searches prompted a reassessment of the 

inclusion criteria. Additionally, the rapid advancements in 

wound healing biomarkers36 underscored the necessity for 

more recent data. A recent scoping review examined 

prognostic factors (biomarkers) associated with ulcer 

healing, a common diabetic complication that can precede 

amputation,37 specifically focused on sources published 

before 2017.38 In light of this context, it was decided to 

include only sources published in or after 2017, thereby 

ensuring the relevance and timeliness of the reviewed 

literature. Search results were exported and managed in 

EndNote 20 (Version 20.2.1, Clarivate, 2021), where 

duplicates were removed.  

 

https://doi.org/10.33137/cpoj.v7i2.43716


 

4 

Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 2 - A scoping review of physical biomarkers. 
Canadian Prosthetics & Orthotics Journal. 2024; Volume 7, Issue 2, No.3. https://doi.org/10.33137/cpoj.v7i2.43716 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X WOUND MANAGEMENT: PHYSICAL BIOMARKERS 

Williams-Reid et al., 2024 

2: DATA EXTRACTION, ANALYSIS, AND PRESENTATION 

Data extraction (including study type and characteristics, 

and physical biomarkers) was performed by the primary 

reviewer using a pre-defined tool for sources that passed 

both screening rounds. The QualSyst tool39 (chosen for its 

quantitative and reproducible quality assessment) and the 

JBI levels of evidence40 were used to evaluate study quality 

and evidence levels respectively. A prevalence of poor-

quality or low-level evidence would indicate the need for 

methodological improvements in biomarker research. All 

extracted data, including references for included sources, 

are openly accessible in the review’s dataset.41 

Due to the nature of a scoping review, a meta-analysis is 

not considered appropriate.30 Instead, basic descriptive 

analyses, such as frequency counts of key concepts, were 

prioritized. Extracted biomarkers were subject to frequency 

counts, and evidence levels and quality scores were 

compiled. The included sources are categorized based on 

study type (randomized controlled trial, case study, 

observational study, or bench research), wound type 

(diabetic, amputation, or other), and model type (human, 

murine, or other, such as cell lines). Each category provides 

distinct insights into wound healing, contributing to a 

comprehensive understanding from multiple perspectives. 

Physical biomarkers that were observed repeatedly, not 

only within categories but also across multiple study 

categories, are visually represented in a tree-map graph 

and are further analyzed in the discussion through 

comparison with existing literature. This manuscript focuses 

on these recurring biomarkers, based on the assumption 

that repetition indicates a stronger evidence base for the 

biomarker’s use, thus supporting further research on these 

biomarkers. A separate descriptive section summarizes the 

methodologies for biomarker quantification. 

RESULTS 

1: OVERALL RESULTS  

1.1: Search Strategy Results 

As detailed in Part 1,23 the search strategy implemented in 

May 2023 resulted in the identification of 7,041 sources. 

Following the removal of 3,735 duplicate records, a total of 

3,306 titles and abstracts were screened (see Part 1 for the 

PRIMSA diagram23). Ultimately, 219 articles were selected 

for data extraction. Exclusions were based on factors such 

as review articles study type, unclear methodologies, and 

lack of ethical approval. Of the 219 articles selected, 157 

reported on physical biomarkers, and were therefore the 

focus of this Part 2 review.  

 

Table 1: Overview of the study types of all 157 included sources utilizing physical biomarkers. The table categorizes the included sources by 

study type, wound type, and model type and provides the reference number for the category used throughout the review. The number of 

included sources and percentage of the 157 included sources in each category are detailed. 

Study Type 

Category 

Reference 

Number 

Number (%) of 

Included 

Sources 

Included Source References 

Randomised Controlled Trial 1 7 (4%) 42, 135, 156, 172, 193, 194, 196 

Case-Controlled Study 2 3 (2%) 149, 151, 162 

Observational 

Prospective 

Diabetic Wounds 3 14 (9%) 
45, 54, 138, 140, 141, 143, 153, 

173, 176, 178, 182, 188, 191, 192 

Amputation 4 5 (3%) 44, 137, 139, 179, 198 

Other Wounds 5 9 (6%) 
46-48, 144, 146, 152, 161, 164, 

181 

Retrospective 

Diabetic Wounds 6 13 (8%) 
43, 70, 113, 130, 133, 134, 147, 

148, 160, 163, 165, 168, 175 

Amputation 7 14 (9%) 
128, 132, 142, 145, 166, 169, 

177, 180, 183-185, 187, 189, 195 

Other Wounds 8 13 (8%) 
136, 150, 154, 155, 157-159, 167, 

170, 171, 174, 186, 190 

Bench Research 

Diabetic 

Wounds 

Rat Models 9 22 (14%) 

50, 59, 68, 71, 80, 81, 83, 86, 89, 

91, 94, 97, 98, 100, 106, 108, 

111, 112, 114, 116, 119, 123 

Mouse Models 10 36 (23%) 

49, 52, 53, 57, 60, 61, 63-65, 69, 

72, 73, 77-79, 82, 85, 87, 88, 90, 

93, 95, 102, 103, 109, 110, 115, 

117, 121, 122, 124-126, 129, 131, 

197 

Other Models 11 5 (3%) 58, 62, 74, 75, 96 

Other 

Wounds 

Rat/Mouse 

Models 
12 13 (8%) 

51, 55, 56, 66, 67, 76, 84, 92, 99, 

101, 104, 105, 118 

Other Models 13 3 (2%) 107, 120, 127 

 

https://doi.org/10.33137/cpoj.v7i2.43716


 

5 

Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 2 - A scoping review of physical biomarkers. 
Canadian Prosthetics & Orthotics Journal. 2024; Volume 7, Issue 2, No.3. https://doi.org/10.33137/cpoj.v7i2.43716 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X WOUND MANAGEMENT: PHYSICAL BIOMARKERS 

Williams-Reid et al., 2024 

1.2: Quality and Levels of Evidence 

For a detailed reporting and discussion of the quality and 

levels of evidence of all 219 sources that meet the inclusion 

criteria for the overall review aim, please refer to Part 1.23 

The levels of evidence across the 157 included sources 

were variable encompassing both the highest and lowest 

tiers of evidence. For instance, within the Effectiveness 

category, only 1 study42 (of 157 included sources) was 

graded as 1.b, and 6 studies43-48 received a grade of 1.c; 

however, a significant majority, 79 sources49-127 were rated 

at 5.c (the lowest level of evidence). 

All studies evaluated were quantitative, with none receiving 

a limited quality score. Specifically, 79% of all studies were 

demonstrated strong quality,43,44,46,47,49-52,54,55,57-63,67-71,74,76-

81,91-99,101-108,111,115,117,118,121-187 19% were rated as good 

quality,42,45,53,56,64-66,72,73,89,90,100,109,110,112-114,116,119,188-197 and 

only 4% were classified as adequate quality.48,75,120,198  

1.3: Study Types and Characteristics 

Of the 157 included sources, 79 were classified as bench 

research studies (Table 1- Study Categories 9 to 13), while only 

3 were identified as case-controlled studies.149,151,162 This 

data was further analyzed based on wound type and model 

type (Table 1). Notably, bench research studies focusing on 

diabetic wounds using mouse models constituted the 

largest study category, comprising 36 sources. 

In Categories 1 to 8 (Table 1), human participants were 

employed, with sample sizes ranging from a minimum of 2 

(a case-controlled study151) to 7,187 (an observational 

retrospective study145). Within the human participant studies 

that provided gender information (71 of 78 sources) sample 

genders ranged from a minimum of 20% male161 to 99% 

male145 (Table 2). Medians of the mean ages were all above 

60 years, with means ranging from 27.1146 years to 77.3 

years.195 In some sources, age was instead described by 

ranges and median ages (Table 2). 34 (44%) of the 78 

human participant studies investigated diabetic wounds, 21 

(27%) focused on amputations (some of which were a result 

of a diabetic wound), and 23 (29%) investigated other 

wounds (Table 2). Examples of other wounds included acute 

lower extremity wounds,196 anterior cruciate ligament tear 

reconstruction,199 chronic foot ulcers,47,190 and 

appendectomy surgical sites.167 

The synthesis of the 79 bench research studies (Study 

Categories 9 to 13) revealed complex sample 

characteristics. Among the 71 studies employing rat or 

mouse models, 46 (65%) used exclusively male rodents, 7 

(10%) used only females, and the remainder either did not 

specify gender or used both. Seven of the eight studies in 

“other models” (Categories 11 and 13) utilized cell lines 

(animal and human), wound healing assays (scratch 

assays), and/or human tissue samples.58,74,75,96,107,120,127 

The remaining study employed a mathematical model.62 Of 

the 79 bench research studies, 63 (80%) focused on 

diabetic wounds (Table 1- Study Categories 9 to 11), with only 

one study92 examining hind limb amputation in Sprague-

Dawley rats. The remaining 15 studies investigated other 

wounds, including sciatic nerve injuries (cut and crush 

injuries; 2 sources67,84), traumatic injuries (musculoskeletal 

trauma and blast-associated injuries; 3 sources55,104,105), 

skin wounds (7 sources51,56,66,76,99,101,118), and general 

wound cell models (includes wound/scratch assays; 3 

sources107,120,127). 

2: REPEATED PHYSICAL BIOMARKERS 

The most frequently reported physical biomarker was 

histology, which encompasses measures such as collagen 

deposition and the degree of angiogenesis, all determined 

through microscopic analysis of sectioned and stained 

tissue samples. Histology was employed in 64 sources 

representing 41% of the 157 included sources (Table 3 and 

Figure 1). Additional physical biomarkers, utilized not only 

within but also across various source types, included ankle-

brachial index (ABI), oxygenation measures (such as 

TcPO₂ [transcutaneous partial oxygen pressure], SpO₂ 

[peripheral oxygen saturation], and StO₂ [tissue oxygen 

saturation]), perfusion, and blood pressure and pulse 

measurements. These biomarkers were reported in 25 

(11%), 19 (9%), 13 (6%), and 12 (5%) sources, respectively 

(Table 3). 

3: MEASUREMENT TECHNIQUES OF REPEATED 

PHYSICAL BIOMARKERS 

To quantify the repeated physical biomarkers, 

measurement techniques including pulse oximeters, 

immunostaining, and blood pressure cuffs were utilized 

(Table 4). Interestingly, both ABI and perfusion require a 

Doppler ultrasound to be quantified. Estimated glomerular 

filtration rate (eGFR) was generated from serum creatinine 

levels (a routine blood marker) and was therefore calculated 

from routine blood test results. 

DISCUSSION 

1: KEY FINDINGS 

This review identifies predictive, diagnostic, and/or 

indicative physical biomarkers of residual limb healing in 

adults with amputation, providing the foundation for the 

development of a standardized assessment scale for 

monitoring healing progression and prosthetic rehabilitation 

post-amputation.  

Histological analysis, the most frequently reported 

biomarker, diagnoses cellular healing progression by 

quantifying key components such as collagen and 

keratinocyte presence which are crucial for all four wound 

healing phases. However, its need for wound tissue 

samples raises ethical and practical concerns, limiting its 

clinical application. Non-invasive hemodynamic and 

oxygenation biomarkers, such as transcutaneous oximetry, 

oxygen saturation measures, ABI, and skin perfusion 

https://doi.org/10.33137/cpoj.v7i2.43716


 

6 

Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 2 - A scoping review of physical biomarkers. 
Canadian Prosthetics & Orthotics Journal. 2024; Volume 7, Issue 2, No.3. https://doi.org/10.33137/cpoj.v7i2.43716 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X WOUND MANAGEMENT: PHYSICAL BIOMARKERS 

Williams-Reid et al., 2024 

pressure (SPP), provide valuable information regarding 

tissue oxygenation and vascular health, both of which 

predict and indicate healing outcomes. While eGFR serves 

as an indirect marker of kidney function that influences the 

healing process, it does not directly reflect the underlying 

mechanisms of healing. It identifies a comorbidity that may 

predict impaired healing, thus rendering it less useful for 

post-amputation assessments but valuable for pre-

amputation risk assessment.  

To enhance monitoring capabilities, there is a need for 

improved biomarker quantification techniques, such as the 

development of wearable sensors, as well as the utilization 

of multiple objective biomarkers to address the complex 

health considerations (comorbidities and heterogeneity) of 

individuals with amputation. There is a need for future 

research to determine biomarker threshold values for 

predicting, diagnosing, and indicating healing, ensuring 

their safe and effective application in the amputee 

population.  

2: REPEATED PHYSICAL BIOMARKERS 

2.1: Physical Biomarkers 

Histological analysis, utilizing techniques such as tissue 

sectioning, staining, and microscopic examination, provides 

cellular-level visual evidence of healing.200 Techniques like 

Masson’s trichrome staining quantify collagen content,201 a 

crucial regulator in all wound healing phases.202 During the 

hemostasis phase, collagen promotes platelet activation 

and fibrin clot formation at the injury site. In the inflammatory 

phase, the activation of immune cells leads to the release of 

pro-inflammatory cytokines, which encourage fibroblast 

migration and collagen deposition.202 During proliferation, 

collagen degradation stimulates the production of growth 

factors and fibroblast proliferation, driving angiogenesis and 

re-epithelialization.202 Finally, during maturation, collagen 

composition alterations are essential for tissue remodeling 

and the tensile strength of healed skin. Bibi et al.52 utilized 

histological analysis to show that lapachol-treated mice with 

full-thickness wounds exhibited increased, organized 

collagen deposition and significant wound size reduction by 

days 8 and 10 post-wounding compared to controls  

(p < 0.001). Hematoxylin and eosin (H&E) staining serves 

to assess keratinocyte presence.203 Keratinocytes migrate 

into the wound to repair epidermal defects, and their 

proliferation, regulated by cytokines and growth factors, 

ensures complete wound coverage.204 Ferroni et al.172 

employed H&E staining to assess diabetic foot ulcers 

(DFUs) treated with Therapeutic Magnetic Resonance 

(TMR®). DFUs treated with a non-functioning TMR® device 

exhibited a limited presence of fibroblasts, endothelial cells, 

keratinocytes, and collagen fibers (p < 0.001), which 

correlated with significantly longer healing times.172 The 

DFUs treated with an active TMR® device healed faster, 

averaging 44.8 ± 12.1 days versus 96.7 ± 23.5 days in the 

sham group (p < 0.05).172 Thus, histological analysis serves 

as a critical diagnostic tool for quantifying healing 

progression, particularly through the measurement of 

angiogenesis and collagen deposition at the wound site. 

Estimated glomerular filtration rate (eGFR) is a quantitative 

measure derived from serum creatinine or cystatin C test 

results, serving as an indicator of kidney function by 

assessing the volume of blood filtered by the kidneys per 

minute.205 Its primary application is within observational 

studies concerning diabetic wounds, likely a consequence 

of the detrimental effects of diabetes on renal function.206 

Chronic kidney disease (CKD) is characterized by a 

sustained reduction in eGFR to values below 60 

mL/min/1.73 m² for a duration of three months or longer.207 

The impact of CKD on wound healing is well-documented; 

findings from murine excisional wound models indicate that 

CKD-affected mice present altered blood chemistry and 

hematology profiles, reduced rates of re-epithelialization 

and granulation tissue deposition, and differential 

expression of genes associated with wound healing, 

including vascular endothelial growth factor, interleukin-1 

beta, endothelial nitric oxide synthase, and inducible nitric 

oxide synthase.208 These changes are accompanied by 

significant reductions in cellular proliferation and 

angiogenesis, alongside heightened inflammatory 

responses when compared to control groups.208 Therefore, 

eGFR serves as an indicator of a comorbidity predictive of 

non-healing, making it less useful for post-amputation 

assessments but valuable for pre-amputation evaluations to 

identify patients at higher risk of impaired healing.  

Cell viability is used only in bench research studies 

employing scratch assays, where healing is assessed by 

observing the migration of cells across a created “scratch” 

in the assay. In such studies, it is necessary to ensure the 

health of the cells to validate that the observed migration (or 

lack thereof) is a result of healing mechanisms, rather than 

poor cell culture conditions. Cell viability tests confirm this 

by quantifying the number of live/dead cells and/or the 

metabolic activity of the cells. Kasowanjete et al.74 for 

example, used Trypan blue stain to determine the number 

of viable cells in a cellular wound model investigating the 

impact of photobiomodulation at 660 nm on in vitro diabetic 

wound healing. Dead cells take up the dye due to 

permeable cell membranes, whereas the impermeable 

membranes of viable cells prevent them from taking up the 

dye. Cell viability is therefore diagnostic of cell health, and 

indicative of healing, but offers little clinical applicability to 

the amputee population. Instead, it is limited to use in 

preclinical research to evaluate the efficacy of novel 

therapeutic compounds designed to promote healing, or 

better understand the cellular level mechanisms that control 

healing in residual limb tissue.  

 

https://doi.org/10.33137/cpoj.v7i2.43716


 

7 

Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 2 - A scoping review of physical biomarkers. 
Canadian Prosthetics & Orthotics Journal. 2024; Volume 7, Issue 2, No.3. https://doi.org/10.33137/cpoj.v7i2.43716 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X WOUND MANAGEMENT: PHYSICAL BIOMARKERS 

Williams-Reid et al., 2024 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 2: The characteristics of the included sources involving human participants, specifically wound type, sample size, sample gender, and 

sample age, are detailed for Study Categories 1 to 8 (refer to Table 1). The notation "No. (%) of references" indicates the number and percentage 

of sources that provide characteristic information relative to the total number of sources within that category (T.G. = treatment groups; C.G. = 

control groups; No. = number). 
 Study Category 

1 2 3 4 5 6 7 8 

Wound Type Totals 

Diabetic 
5 (42, 135, 172, 193, 

194) 
2 (149, 151) 

14 (45, 54, 

138, 140, 

141, 143, 

153, 173, 

176, 178, 

182, 188, 

191, 192) 

0 0 

13 (43, 70, 

113, 130, 

133, 134, 

147, 148, 

160, 163, 

165, 168, 

175) 

0 0 

Amputation 1 (156) 1 (162) 0 

5 (44, 137, 

139, 179, 

198) 

0 0 

14 (128, 
132, 142, 
145, 166, 
169, 177, 
180, 183-
185, 187, 
189, 195) 

0 

Other 1 (196) 0 0 0 

9 (46-48, 
144, 146, 
152, 161, 
164, 181) 

0 0 

13 (136, 

150, 154, 

155, 157-

159, 167, 

170, 171, 

174, 186, 

190) 

Sample Size Totals 

Range (Min-

Max) 
16-50 2-58 10-684 10-556 5-735 92-1032 13-7187 45-637 

Median 33 20 66 19 60 232 121 120 

No. (%) of 

References 
7 (100%) 3 (100%) 14 (100%) 5 (100%) 9 (100%) 13 (100%) 14 (100%) 13 (100%) 

Sample Gender (% Male) Totals 

Range (Min-

Max) 
40%-82% 47%-100% 35%-84% 60%-73% 20%-90% 45%-83% 29%-99% 54%-78% 

Median 61% 50% 67% 64% 63% 62% 71% 66% 

No. (%) of 

References 

5 (71%) (42, 135, 156, 

193, 196) 
3 (100%) 

13 (93%) 

(45, 54, 138, 

140, 141, 

143, 153, 

176, 178, 

182, 188, 

191, 192) 

5 (100%) 

8 (89%) (46, 
47, 144, 146, 

152, 161, 
164, 181) 

 

11 (85%) 

(43, 70, 113, 

130, 133, 

134, 160, 

163, 165, 

168, 175) 

14 (100%) 

12 (92%) 

(136, 150, 

154, 155, 

157-159, 

167, 170, 

171, 174, 

186) 

Sample Mean Age (Years) Totals 

Range (Min-

Max) 

T.G.: 55.0-69.0; C.G.: 

52.1-64.7 
60.2-61.5 48.0-67.0 49.0-74.0 27.1-72.6 54.5-72.5 61.5-77.3 56.0-74.9 

Median T.G: 64.2; C.G.: 62.0 60.9 61.2 68.4 65 61.2 66.5 72 

No. (%) of 

References 

6 (86%) (42, 135, 156, 

172, 193, 196) 

2 (67%) (151, 

162) 

13 (93%) 

(45, 54, 138, 

140, 141, 

143, 153, 

173, 176, 

178, 182, 

188, 192) 

4 (80%) (44, 

137, 139, 

198) 

6 (67%) (46, 

47, 144, 146, 

152, 181) 

12 (92%) 

(43, 70, 113, 

130, 134, 

147, 148, 

160, 163, 

165, 168, 

175) 

12 (86%) 

(128, 132, 

142, 145, 

166, 177, 

180, 183, 

184, 187, 

189, 195) 

9 (69%) 

(136, 155, 

157-159, 

170, 171, 

174, 186) 

Sample Age Range (Years) Totals 

Range (Min-

Max) 
NA 45-65 20-89 23-66 28-81 17-96 26-96 NA 

No. (%) of 

References 
NA 1 (33%) (149) 

6 (43%) (45, 

143, 173, 

176, 182, 

191) 

2 (40%) (44, 

179) 

3 (33%) 

(161, 164, 

181) 

5 (38%) 

(147, 148, 

163, 165, 

175) 

4 (29%) 

(177, 180, 

187, 189) 

NA 

Sample Median Age (Years) Totals 

Range (Min-

Max) 
NA NA NA NA NA 72.5 47.0-62.0 31.0-71.2 

Median NA NA NA NA NA 72.5 54.5 68.4 

No. (%) of 

References 
NA NA NA NA NA 1 (8%) (133) 

2 (14%) 

(169, 185) 

3 (23%) 

(150, 154, 

167) 

 

https://doi.org/10.33137/cpoj.v7i2.43716


 

8 

Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 2 - A scoping review of physical biomarkers. 
Canadian Prosthetics & Orthotics Journal. 2024; Volume 7, Issue 2, No.3. https://doi.org/10.33137/cpoj.v7i2.43716 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X WOUND MANAGEMENT: PHYSICAL BIOMARKERS 

Williams-Reid et al., 2024 

 

Table 3: A comprehensive breakdown of the repeated physical biomarkers. A biomarker was considered “repeated” if it was used in more than 

one source within a study category and appeared in more than one study category. The occurrence of these biomarkers in the 157 included 

sources is presented, along with their representation across the various study categories (see Table 1; ABI = ankle-brachial index; TcPO2 = 

transcutaneous oxygen pressure; SpO2 = saturation of peripheral oxygen; StO2 = skeletal muscle oxygen saturation; SPP = skin perfusion 

pressure; SBP = systolic blood pressure; DBP = diastolic blood pressure; eGFR = estimated glomerular filtration rate).  

Repeated Physical 

Biomarkers 

Sources Study Categories 

Frequency 
% of Included 

Sources 
References Frequency 

% of 

Categories 

Categories 

Included 

Histology 64 41% 

50-53, 56, 57, 59-61, 63-68, 71-73, 76-

83, 85-91, 93, 95, 97-103, 106, 108-

112, 114-119, 121-126, 131, 172, 194, 

197 

4 31% 1, 9, 10, 12 

ABI  25 16% 

113, 128, 132, 141, 143, 145, 154, 155, 

157, 161, 163-166, 168, 173, 174, 176, 

181, 183, 186, 188, 192, 193, 196 

6 46% 1, 3, 5, 6, 7, 8 

TcPO2, SpO2, and StO2 19 12% 

45, 48, 54, 70, 113, 132, 139, 141, 144, 

147, 148, 153, 165, 168, 179-181, 188, 

191 

5 38% 3, 4, 5, 6, 7 

Perfusion (includes SPP)  13 8% 
42, 46, 48, 142, 155-157, 161, 164, 170, 

174, 189, 196 
4 31% 1, 5, 7, 8 

Blood Pulse and Pressure 

Measures (includes SBP, 

DBP, Toe Pressure, etc.)  

12 8% 
113, 134, 147, 148, 160, 165, 175, 177, 

187, 188, 192, 195 
3 23% 3, 6, 7 

eGFR 5 3% 43, 133, 138, 168, 173 2 15% 3, 6 

Cell Viability 5 3% 74, 96, 107, 120, 127 2 15% 11, 13 

 
 

 

 
Figure 1: Treemap visualization displaying the frequencies of the repeated physical biomarkers. A biomarker was considered “repeated” if it was 
used in more than one source within a study category and appeared in more than one study category. The occurrence of these biomarkers in 
the 157 included sources is presented as a percentage (ABI = ankle-brachial index; TcPO2 = transcutaneous oxygen pressure; SpO2 = saturation 
of peripheral oxygen; StO2 = skeletal muscle oxygen saturation; SPP = skin perfusion pressure; SBP = systolic blood pressure; DBP = diastolic 
blood pressure; eGFR = estimated glomerular filtration rate). 

Table 4: Measurement techniques reported in included sources used to quantify repeated physical biomarker expression (ABI = ankle-brachial 

index; TcPO2 = transcutaneous oxygen pressure; SpO2 = saturation of peripheral oxygen; StO2 = skeletal muscle oxygen saturation; SPP = skin 

perfusion pressure; SBP = systolic blood pressure; DBP = diastolic blood pressure; eGFR = estimated glomerular filtration rate; H&E = 

hematoxylin and eosin; MTT = 3-[4,5-Dimethylthiazol-2-yl]-2,5-Diphenyltetrazolium Bromide). 

Repeated Physical Biomarkers Biomarker Measurement Techniques 

Histology 
Immunostaining of sectioned wound tissue samples using toluidine blue, Masson’s trichrome 

stain, H&E stain, and primary antibody stains.  

ABI  Vascular Doppler ultrasound. 

TcPO2, SpO2, and StO2 Percutaneous oxygen partial pressure detector. 

Perfusion (includes SPP)  Laser Doppler probe and blood pressure cuff.  

Blood Pulse and Pressure Measures (includes SBP, DBP, 

toe pressure etc.)  
Pulse oximeter.  

eGFR Calculated from routine blood test results. 

Cell Viability 
MTT (3-[4,5-Dimethylthiazol-2-yl]-2,5-Diphenyltetrazolium Bromide) assay, Trypan blue exclusion 

assay, and live/dead cell staining. 

 

Treemap Representation of the Repeated Physical Biomarkers 

Histology, 41% 

 

ABI, 16% 

TcPO2, SpO2, and StO2, 12% 

Perfusion (includes SPP), 

                   8% 

Blood Pulse and Pressure 

Measures (includes SBP, 

DBP, toe, etc.), 8% 

eGFR, 3% 
Cell 

Viability, 3% 

https://doi.org/10.33137/cpoj.v7i2.43716


 

9 

Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 2 - A scoping review of physical biomarkers. 
Canadian Prosthetics & Orthotics Journal. 2024; Volume 7, Issue 2, No.3. https://doi.org/10.33137/cpoj.v7i2.43716 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X WOUND MANAGEMENT: PHYSICAL BIOMARKERS 

Williams-Reid et al., 2024 

Transcutaneous oxygen pressure (or transcutaneous 

oximetry [TcPO2]), peripheral oxygen saturation (or pulse 

oximetry [SpO2]), and skeletal muscle oxygen saturation 

(StO2) are non-invasive metabolic measures that provide 

insight into tissue oxygenation levels.209 Oxygen is critical 

for wound healing, influencing various stages of the healing 

process under both hypoxic and normoxic conditions.209 

During the hemostasis phase, hypoxia plays a pivotal role 

in initiating the wound healing process by enhancing the 

activity of reactive oxygen species (ROS).210 In the 

inflammation phase, the elimination of bacteria occurs via 

phagocytosis, a process contingent upon high partial 

oxygen pressure.211 Vascular endothelial growth factor, a 

key growth factor in angiogenesis, is upregulated by 

hypoxia-inducible factor 1-alpha, which is activated by both 

hypoxia and ROS during the proliferation phase. In the 

maturation phase, which includes tissue remodeling, 

oxygen facilitates keratinocyte activity through ROS.211 Loo 

and Halliwell212 utilized a keratinocyte-fibroblast co-culture 

model of wound healing, to demonstrate hydrogen peroxide 

(H2O2), a common ROS, enhanced keratinocyte 

proliferation and accelerated the rate of epithelialization. 

Oxygen is evidently vital for facilitating cellular activity and 

tissue repair during healing, however techniques for 

assessing oxygen levels differ. For example, TcPO2 non-

invasively quantifies local tissue perfusion via 

electrochemical sensors,213 with calf values exceeding 40 

mmHg associated with a higher percentage of successful 

healing after below-the-knee amputation.214 Similarly, a 

retrospective study found a statistically significant 

relationship (p < 0.001) between lower TcPO2 values and 

prolonged wound healing duration in 84 patients with critical 

limb-threatening ischemia.132 Contrastingly, StO2 is 

assessed non-invasively through measurements of 

oxyhemoglobin and deoxyhemoglobin using near-infrared 

spectroscopy.215 Lee et al.216 demonstrated that skin 

wounded by pressure injuries exhibited a significantly 

higher median StO2 compared to healthy and scabbed skin. 

Thus, oxygenation measures function as predictive and 

indicative markers of healing post-amputation. They may 

also predict risk of further wounds to the residuum like deep 

tissue injury (DTI), caused by reduced oxygen levels 

resulting from vascular occlusions induced by loading 

during lower limb prosthetic use.217  

The hemodynamic biomarkers, ankle-brachial index (ABI), 

perfusion, and blood pulse and pressure measures, indicate 

the vascular status surrounding a wound. Insufficient 

perfusion, characterized by poor macro-circulation, 

increases progressive hypoxia risk and diminishes nutrient 

and survival factors delivery necessary for tissue repair.218 

This impairs processes such as angiogenesis, collagen 

deposition, and epithelialization, resulting in sustained 

inflammation. The angiogenesis phase of wound healing 

involves the formation of new blood vessels that supply 

nutrients, immune cells, and oxygen to the wound site.219 It 

is characterized by an initial period of rapid and excessive 

capillary growth that eventually regresses to a vascular 

density akin to that of normal skin.219 Therefore, 

hemodynamic measures are predictive and indicative of 

healing. For example, a systematic review indicated that an 

ABI value of less than 0.5 in patients with DFUs, calculated 

as the ratio of blood pressure in an ankle artery to that in an 

arm artery, was significantly associated with an increased 

incidence of major amputation.220 Skin perfusion pressure 

(SPP) of ≥ 40 mmHg and toe pressure of ≥ 30 mmHg (or ≥ 

45 mmHg) were also linked to at least a 25% higher 

likelihood of healing. Similarly, a study of 81 diabetic 

patients concluded that normal ABI (0.90-1.30) correlated 

with successful healing (p < 0.05), while ABI (≤ 0.40) was 

associated with failed transmetatarsal amputation  

(p < 0.01).183  

While valuable, hemodynamic measure interpretations 

vary. For instance, SPP evaluates vascularity by assessing 

the blood pressure required to restore microcirculatory or 

capillary flow after controlled occlusion, while ABI reflects 

the ratio of the ankle to arm blood pressure. The contrasting 

literature regarding each biomarker must be addressed. For 

example, calf TcPO2 values above 40 mmHg are associated 

with improved healing outcomes after below-the-knee 

amputation, while values below 20 mmHg correlate with 

poorer healing.214 However, a 2012 meta-analysis found 

insufficient evidence to establish an optimal TcPO2 

threshold value for lower limb amputation clinical use.25, 214 

This review identifies the physical biomarkers commonly 

used in wound healing literature but highlights the need for 

further research to determine their threshold values, safety, 

and applicability in the amputee population.  

2.2: Quantification Techniques 

The application of physical biomarkers in the proposed 

residual limb healing assessment scale is influenced by the 

methods used to quantify these biomarkers. Histological 

analysis offers the most detailed and diagnostic view of 

wound healing progression, but its quantification technique 

presents significant challenges. The requirement for wound 

tissue collection restricts histology’s use primarily to bench 

research in animal models, as ethical concerns limit the use 

of human tissue samples.221 For example, in animal studies, 

such as that of Bibi et al.,52 tissue samples were collected 

at defined intervals (days 3, 7, and 10 post-wounding), 

allowing discrete snapshots of healing progression.  

Conversely, hemodynamic and oxygenation measures 

were predominantly utilized in human participant studies, 

likely due to their non-invasive measurement techniques,222 

ease of use, and incorporation into established clinical 

practice, such as ABI for peripheral arterial disease (PAD) 

assessment.223 Their non-invasive measurement 

techniques are however not immune to limitations. For 

example, ABI measurements require pressure to be applied 

to the limb, which can be painful in patients with ischemia or 

https://doi.org/10.33137/cpoj.v7i2.43716


 

10 

Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 2 - A scoping review of physical biomarkers. 
Canadian Prosthetics & Orthotics Journal. 2024; Volume 7, Issue 2, No.3. https://doi.org/10.33137/cpoj.v7i2.43716 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X WOUND MANAGEMENT: PHYSICAL BIOMARKERS 

Williams-Reid et al., 2024 

wounds,222 both of which are associated with 

amputation.224,225 TcPO2 measurements require the use of 

heated electrodes to enhance vasodilation,214 which may 

pose a risk of damaging sensitive post-operative residual 

limbs. Pulse oximetry is limited by poor peripheral perfusion, 

motion artefacts, and variations in skin pigmentation.226 

These limitations introduce the need for improved 

biomarker quantification techniques specifically suited for 

residual limb monitoring, such as wearable wound healing 

sensors. For instance, Ochoa et al.227 are developing an 

integrated smart wound dressing capable of sensing and 

delivering oxygen to the wound. 

Alternatively, employing a combination of biomarkers could 

provide a more comprehensive view of residual limb 

healing. Biomarkers are typically not exclusive to healing. 

For example, patients with lower extremity PAD, a common 

comorbidity among amputees,228 often present with TcPO2 

calf values below 40 mmHg, while values above this 

threshold are generally associated with successful residual 

limb healing after below-the-knee amputation.214 To 

account for the comorbidities prevalent in the amputee 

population, multiple biomarkers should be utilized to provide 

a holistic view of residual limb health. 

3: OVERALL SEARCH RESULTS AND STUDY 

CHARACTERISTICS 

Most reviewed sources focused on diabetic wounds, a 

reflection of the global burden of diabetes, with an estimated 

529 million individuals living with diabetes worldwide in 

2021.229 DFUs are the most common complication of 

diabetes230 and a significant risk factor for amputation.231,232 

For example, the Scottish Physiotherapy Amputee 

Research Group (SPARG) “Survey of the Lower Limb 

Amputee Population in Scotland 2019 Public Report” noted 

that over half (56%) of all lower limb amputees had the 

etiology of diabetes.233 Pre-amputation assessment is 

especially critical for patients with a greater number of 

comorbidities, such as diabetes, and suboptimal 

physiological factors known to predict wound 

complications.12 Diabetes can impair wound healing via 

hyperglycemia-induced vascular stiffening, microvascular 

dysfunction, and reduced oxygenation.18 Therefore, 

physical biomarkers may enhance pre-amputation 

assessments to improve post-amputation outcomes.  

Age is another key factor affecting healing, with medians of 

the mean participant ages in included human studies 

ranging from 60.9 to 70.0 years, highlighting a 

predominance of older adults. Most non-healing wounds are 

a result of vascular disease,234 venous insufficiency,235 

areas of high unrelieved pressure,236 diabetes,237 and 

disability;238 conditions that are increasingly prevalent as 

the population ages. For instance, Public Health England 

reports diabetes prevalence rising from 9.0% among 

individuals aged 45 to 54 years to 23.8% among those aged 

75 years and over.237 Age-related factors, such as 

prolonged inflammation and increased production of 

reactive oxygen species during healing, can lead to chronic 

wounds.239 This aging effect is also reflected in the SPARG 

2019 report, which found the median age at the time of 

lower limb amputation to be 67 years.233 As aging 

exacerbates healing complications and delays recovery, 

there is a critical need for objective measures of wound 

healing to accelerate prosthetic fitting and improve 

outcomes.  

Gender also plays a significant role in predicting wound 

complications. An analysis of gender characteristics across 

human participant studies revealed that the median 

proportion of male participants ranged from 50% to 71%. 

Male gender is a risk factor for DFU development,240 poorer 

DFU healing,241 increased post-surgical infection rates,242 

and higher in-hospital immortality rates after trauma.243 In 

the SPARG 2019 report, 71.5% of lower limb amputees 

were male,233 though studies also indicate that women may 

be less likely to successfully receive a lower limb prosthesis 

after amputation.244 These disparities highlight the need for 

gender-specific research245 and biomarkers not influenced 

by hormonal or gender-related factors.  

Most studies did not investigate wound healing after 

amputation but focused on wounds in patient populations 

similar to those who undergo amputation, highlighting the 

lack of standardized approaches and understanding of the 

tissue changes that occur in residual limbs post-amputation. 

By extrapolating findings from wound healing studies in 

tissues and structures found in residual limbs, a 

foundational database of potential biomarkers can be 

established for use in residual limb healing. Notably, all 

studies on amputation included in this review examined 

lower limbs, which account for 4-5 times more amputations 

than upper limbs246 and face unique residual limb health 

requirements due to weight-bearing requirements during 

ambulation.  

4: METHODOLOGICAL DISCUSSION 

4.1: Methodological Strengths 

A broad exploration of the literature on biomarkers related 

to healing is provided in this review, allowing for the 

inclusion of diverse sources without strict criteria, unlike a 

systematic review which requires a focused research 

question. Instead, the findings can serve as a basis for 

subsequent systematic review, such as Johnson et al.’s 

review of IL-6 in wound healing,247 particularly if high-quality 

evidence on a specific biomarker emerges.  

A notable strength of this review lies in its emphasis on the 

potential impact of biomarkers on the future of post-

amputation healing and rehabilitation. By identifying 

physical biomarkers capable of diagnosing, identifying, or 

predicting healing, a starting point for further research into 

https://doi.org/10.33137/cpoj.v7i2.43716


 

11 

Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 2 - A scoping review of physical biomarkers. 
Canadian Prosthetics & Orthotics Journal. 2024; Volume 7, Issue 2, No.3. https://doi.org/10.33137/cpoj.v7i2.43716 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X WOUND MANAGEMENT: PHYSICAL BIOMARKERS 

Williams-Reid et al., 2024 

objective healing measures and quantification 

methodologies is provided. This moves us closer to a 

specific post-amputation residuum healing assessment 

scale, which may enable more timely healing interventions, 

enhancing non-healing prevention and treatment 

strategies.248 

4.2: Methodological Limitations 

In this section limitations associated with specific study 

types, not explored in the Part 1 review,23 are discussed. 

Animal studies, despite genetic similarities to humans, often 

lack reliability due to biological differences and 

methodological issues,249 while mathematical models, 

although based on empirical data, can oversimplify the 

complexities of human biological processes.250-252 

Consequently, biomarker behavior observed in both should 

be interpreted cautiously, serving as potential indicators 

rather than definitive predictors of human responses. All 

wound types affecting tissues relevant to the residuum were 

considered appropriate for inclusion in this review, however, 

future research needs to account for the differences 

between secondary intention healing wounds, like DFUs, 

and primary intention wounds, such as sutured surgical 

sites, when applying findings to clinical contexts.  

 The synthesis of data from diverse sources in scoping 

reviews risks oversimplification or loss of critical detail. 

Biomarkers that appeared repeatedly within and across 

different study types were prioritized for discussion in this 

review. However, this approach excludes biomarkers in only 

a single study or specific category. For example, Alfawaz et 

al.184 investigated tibial vessel run-off (VRO) and popliteal 

artery patency, reporting that higher VRO was associated 

with improved healing rates and shorter time to healing 

following below-knee amputation, and that preoperative 

popliteal patency was linked to higher postoperative 

ambulation rates. The study's solitary use of these 

biomarkers led to its exclusion from broader discussions. 

Yet, these findings suggest potential areas for future 

research given the statistically significant outcomes 

reported.184 

The timing of biomarker quantification critically affects its 

diagnostic value; for example, hypoxia (low oxygen levels) 

is essential at the onset of healing, but prolonged low 

oxygen levels impeded healing.253 Future research should 

address the form of the biomarkers, the timing of their 

measurement, and the anatomical locations from which 

they are sampled to improve their relevance in clinic. 

5: ETHICAL CONSIDERATIONS 

In this review, evidence level was not utilized as an 

exclusion criterion, recognizing that recognizing that 

randomized controlled trials are the highest standard of 

evidence but are limited by high costs, restricted funding, 

and potential industry bias favoring positive results.254 

Instead, the review focused on ensuring that all included 

studies clearly stated ethical approval and obtained 

informed consent from human participants, prioritizing 

ethical standards over rigid adherence to evidence 

hierarchies. Adulthood was defined as aged 18 years or 

older, acknowledging that global variations in defining 

adulthood exist (16 to 21 years),255 to prevent 

misinterpretation in international dissemination. Despite 

efforts to include grey literature in this review to broaden the 

scope and minimize bias,256 none of the sources identified 

met the inclusion criteria, primarily due to insufficient 

methodological transparency and the absence of explicit 

ethical approval. 

CONCLUSION 

This scoping review aimed to identify predictive, diagnostic, 

and/or indicative physical biomarkers of healing within the 

tissues and structures of residual limbs in adults with 

amputation.  The integration of various physical biomarkers 

into the assessment of healing in residual limbs post-

amputation is paramount for optimizing patient outcomes. 

Histological analysis remains the gold standard diagnostic 

biomarker for evaluating cellular healing processes, 

particularly through the measurement of collagen and 

keratinocyte presence, but is limited by the ethical and 

practical challenges of using tissue samples from human 

subjects. Non-invasive indicative and predictive 

oxygenation and hemodynamic measures, such as 

transcutaneous oxygen pressure (TcPO₂) and ankle-

brachial index (ABI), provide valuable insights into tissue 

oxygenation and vascular health; however, further research 

is essential to establish specific threshold values and 

applicability within the amputee population. While the 

estimated glomerular filtration rate (eGFR) serves as an 

indirect marker of kidney function that influences the healing 

process, it does not directly reflect the underlying 

mechanisms of healing. Instead, it identifies comorbidities 

that may predict impaired healing, rendering it less useful 

for post-amputation assessments compared to other 

physical biomarkers. Nevertheless, eGFR remains 

advantageous for pre-amputation evaluations, particularly 

for identifying patients at heightened risk for impaired 

healing.  

The findings underscore the global burden of diabetes, the 

role of age and gender disparities in wound healing, and the 

need for targeted research addressing these factors to 

improve post-amputation outcomes. Most included sources 

focused on wounds in populations common to those 

undergoing amputation, rather than directly examining post-

amputation wound healing, highlighting a lack of 

understanding of the tissue changes that occur in residual 

limbs post-amputation. Developing a holistic residual limb 

specific healing assessment scale that integrates a diverse 

array of physical biomarkers (accounting for physiological 

factors and comorbidities known to influence healing) could 

https://doi.org/10.33137/cpoj.v7i2.43716


 

12 

Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 2 - A scoping review of physical biomarkers. 
Canadian Prosthetics & Orthotics Journal. 2024; Volume 7, Issue 2, No.3. https://doi.org/10.33137/cpoj.v7i2.43716 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X WOUND MANAGEMENT: PHYSICAL BIOMARKERS 

Williams-Reid et al., 2024 

substantially enhance our understanding of the healing 

process and inform the development of effective 

rehabilitation strategies for individuals undergoing 

amputation. 

ACKNOWLEDGEMENTS 

The author of this article would like to express appreciation to the 

Strathclyde Body Device Interface Mechanobiology Research 

Group for their assistance in the discussion of the review’s 

methodology. 

DECLARATION OF CONFLICTING INTERESTS 

The author has no conflicts of interest to declare. 

AUTHORS CONTRIBUTION 

• Hannelore Williams-Reid: the primary author of the 

manuscript, undertook the scoping review and prepared the 

final manuscript as part of a 4-year PhD program.  

• Arjan Buis: the primary PhD supervisor, assisted in developing 

the scoping review methodology and preparing the manuscript 

for publication. 

• Anton Johannesson: the secondary PhD supervisor, assisted 

in developing the scoping review methodology and preparing 

the manuscript for publication. 

 

All authors have read and approved the final version of the 

manuscript. 

 

SOURCES OF SUPPORT 

The PhD project under which this scoping review/manuscript falls 

is funded by the UKRI EPSRC as part of the Centre of Doctoral 

Training (CDT) in Prosthetics and Orthotics (P&O) (studentship 

2755854 "Wound management and early prosthetic rehabilitation" 

within project EP/S02249X/1) and by Össur. 

REFERENCES 

1.Herman TF, Bordoni B. Wound Classification. Wound 

Classification [Internet]. StatPearls. 2024; [cited 2024, July 5]. 

Available from: https://www.ncbi.nlm.nih.gov/books/NBK554456/ 

2.Wallace HA BB, Zito PM. Wound Healing Phases [Internet]. 

StatPearls. 2023; [cited 2024, July 5]. Available from: 

https://www.ncbi.nlm.nih.gov/books/NBK470443/ 

3.Stroncek JD, Reichert WM. Overview of wound healing in 

different tissue types. In: Reichert WM, editor. Indwelling neural 

implants: Strategies for contending with the in Vivo Environment. 

Boca Raton (FL): CRC Press/Taylor & Francis; 2008. Chapter 1. 

Available from: https://www.ncbi.nlm.nih.gov/books/NBK3938/ 

4.Guo S, Dipietro LA. Factors affecting wound healing. J Dent Res. 

2010;89(3):219-29. DOI:10.1177/0022034509359125  

5.Armstrong DG, Meyr AJ. Risk factors for impaired wound healing 

and wound complications. Wolters Kluwer; 2023 [Available from: 

https://www.uptodate.com/contents/risk-factors-for-impaired-

wound-healing-and-wound-complications 

6.Kumar D, Singh S, Shantanu K, Goyal R, Kushwaha NS, Gupta 

AK, et al. Need of revision of lower limb amputations in a north 

Indian tertiary care centre. J Clin Diagn Res. 2015;9(12):Rc01-3. 

DOI:10.7860/jcdr/2015/16385.6886  

7.Choo YJ, Kim DH, Chang MC. Amputation stump management: 

A narrative review. World J Clin Cases. 2022;10(13):3981-8. 

DOI:10.12998/wjcc.v10.i13.3981  

8.Johannesson A, Larsson GU, Oberg T, Atroshi I. Comparison of 

vacuum-formed removable rigid dressing with conventional rigid 

dressing after transtibial amputation: Similar outcome in a 

randomized controlled trial involving 27 patients. Acta Orthop. 

2008;79(3):361-9. DOI:10.1080/17453670710015265  

9.Miller TA, Paul R, Forthofer M, Wurdeman SR. Impact of time to 

receipt of prosthesis on total healthcare costs 12 months 

postamputation. Am J Phys Med Rehabil. 2020;99(11):1026-31. 

DOI:10.1097/phm.0000000000001473  

10.Geertzen JH, Martina JD, Rietman HS. Lower limb amputation. 

Part 2: Rehabilitation-A 10 year literature review. Prosthet Orthot 

Int. 2001;25(1):14-20. DOI:10.1080/03093640108726563  

11.Singh RK, Prasad G. Long-term mortality after lower-limb 

amputation. Prosthet Orthot Int. 2016;40(5):545-51. 

DOI:10.1177/0309364615596067  

12.Day JD, Dionne CP, James S, Wang H. Determinants of healing 

and readiness for prosthetic fitting after transtibial amputation: 

Integrative literature review. Prosthet Orthot Int. 2023;47(1):43-53. 

DOI:10.1097/pxr.0000000000000163  

13.Optimising the timing for prosthetic fitting [Internet]. Bush & Co. 

2024; [cited 2024, July 5]. Available from: 

https://www.bushco.co.uk/news/optimal-time-for-fitting-a-

prosthetic.html 

14.Turner S, Belsi A, McGregor AH. Issues faced by prosthetists 

and physiotherapists during lower-limb prosthetic rehabilitation: A 

thematic analysis. Front Rehabil Sci. 2021;2:795021. DOI:10. 

3389/fresc.2021.795021 

15.Kwah LK, Webb MT, Goh L, Harvey LA. Rigid dressings versus 

soft dressings for transtibial amputations. Cochrane Database Syst 

Rev. 2019;6(6):Cd012427. DOI:10.1002/14651858.CD012427. 

pub2  

16-Safari MR, Rowe P, McFadyen A, Buis A. Hands-off and hands-

on casting consistency of amputee below knee sockets using 

magnetic resonance imaging. ScientificWorldJournal. 2013;2013: 

486146. DOI:10.1155/2013/486146 

17.Molina CA, Faulk J. Lower extremity amputation [Internet]. 

StatPearls Publishing. 2022; [cited 2024, July 5].  Available from: 

https://www.ncbi.nlm.nih.gov/books/NBK546594/ 

18.Spampinato SF, Caruso GI, De Pasquale R, Sortino MA, Merlo 

S. The treatment of impaired wound healing in diabetes: Looking 

among old drugs. Pharmaceuticals (Basel). 2020;13(4). DOI: 

10.3390/ph13040060  

19.Focus Area: Biomarkers [Internet]. FDA (U.S. Food and Drug 

Administration). 2022; [cited 2024, July 5].  Available from: 

https://www.fda.gov/science-research/focus-areas-regulatory-

science-report/focus-area-biomarkers 

20.Bramley JL, Worsley PR, Bader DL, Everitt C, Darekar A, King 

L, et al. Changes in tissue composition and load response after 

https://doi.org/10.33137/cpoj.v7i2.43716
https://www.ncbi.nlm.nih.gov/books/NBK554456/
https://www.ncbi.nlm.nih.gov/books/NBK470443/
https://www.ncbi.nlm.nih.gov/books/NBK3938/
https://www.uptodate.com/contents/risk-factors-for-impaired-wound-healing-and-wound-complications
https://www.uptodate.com/contents/risk-factors-for-impaired-wound-healing-and-wound-complications
https://www.bushco.co.uk/news/optimal-time-for-fitting-a-prosthetic.html
https://www.bushco.co.uk/news/optimal-time-for-fitting-a-prosthetic.html
https://www.ncbi.nlm.nih.gov/books/NBK546594/
https://www.fda.gov/science-research/focus-areas-regulatory-science-report/focus-area-biomarkers
https://www.fda.gov/science-research/focus-areas-regulatory-science-report/focus-area-biomarkers


 

13 

Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 2 - A scoping review of physical biomarkers. 
Canadian Prosthetics & Orthotics Journal. 2024; Volume 7, Issue 2, No.3. https://doi.org/10.33137/cpoj.v7i2.43716 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X WOUND MANAGEMENT: PHYSICAL BIOMARKERS 

Williams-Reid et al., 2024 

transtibial amputation indicate biomechanical adaptation. Ann 

Biomed Eng. 2021;49(12):3176-88. DOI:10.1007/s10439-021-

02858-0  

21.Sanders JE, Fatone S. Residual limb volume change: 

systematic review of measurement and management. J Rehabil 

Res Dev. 2011;48(8):949-86. DOI:10.1682/jrrd.2010.09.0189  

22.Bhutda S, Surve MV, Anil A, Kamath K, Singh N, Modi D, et al. 

Histochemical Staining of Collagen and Identification of Its 

Subtypes by Picrosirius Red Dye in Mouse Reproductive Tissues. 

Bio Protoc. 2017;7(21):e2592. DOI:10.21769/BioProtoc.2592  

23. Williams-Reid H, Johannesson A, Buis A. Wound management, 

healing, and early prosthetic rehabilitation: Part 1 - A scoping review 

of healing and non-healing definitions. Can Prosthet Orthot J. 

2024;7. DOI:10.33137/cpoj.v7i2.43715  

24.Patel S, Ershad F, Zhao M, Isseroff RR, Duan B, Zhou Y, et al. 

Wearable electronics for skin wound monitoring and healing. Soft 

Sci. 2022;2. DOI:10.20517/ss.2022.13 

25. Arsenault KA, Al-Otaibi A, Devereaux PJ, Thorlund K, Tittley JG, 

Whitlock RP. The use of transcutaneous oximetry to predict healing 

complications of lower limb amputations: A systematic review and 

meta-analysis. Eur J Vasc Endovasc Surg. 2012;43(3):329-36. 

DOI:10.1016/j.ejvs.2011.12.004  

26.Boniface M, Burns D, Duckworth C, Ahmed M, Duruiheoma F, 

Armitage H, et al. COVID-19 Oximetry @home: Evaluation of 

patient outcomes. BMJ Open Qual. 2022;11(1). 

DOI:10.1136/bmjoq-2021-001584 

27.Park YR, Shin YK, Eom JB. Non-contact oxygen saturation 

monitoring for wound healing process using dual-wavelength 

simultaneous acquisition imaging system. Biomed Eng Lett. 

2023;13(3):1-9. DOI:10.1007/s13534-023-00275-x  

28.PRISMA for Scoping Reviews [Internet]. PRISMA. 2024; [cited 

2024, July 5]. Available from: https://www.prisma-

statement.org/scoping 

29. Tricco AC, Lillie E, Zarin W, O'Brien KK, Colquhoun H, Levac D, 

et al. PRISMA extension for scoping reviews (PRISMA-ScR): 

Checklist and explanation. Ann Intern Med. 2018;169(7):467-73. 

DOI:10.7326/m18-0850 

30.Peters MDJ, Marnie C, Tricco AC, Pollock D, Munn Z, Alexander 

L, et al. Updated methodological guidance for the conduct of 

scoping reviews. JBI Evid Synth. 2020;18(10):2119-26. 

DOI:10.11124/jbies-20-00167  

31.Pollock D, Davies EL, Peters MDJ, Tricco AC, Alexander L, 

McInerney P, et al. Undertaking a scoping review: A practical guide 

for nursing and midwifery students, clinicians, researchers, and 

academics. J Adv Nurs. 2021;77(4):2102-13. DOI:10.1111/jan. 

14743  

32.Pollock D, Peters MDJ, Khalil H, McInerney P, Alexander L, 

Tricco AC, et al. Recommendations for the extraction, analysis, and 

presentation of results in scoping reviews. JBI Evid Synth. 

2023;21(3):520-32. DOI:10.11124/jbies-22-00123  

33.Khalil H, Peters MD, Tricco AC, Pollock D, Alexander L, 

McInerney P, et al. Conducting high quality scoping reviews-

challenges and solutions. J Clin Epidemiol. 2021;130:156-60. 

DOI:10.1016/j.jclinepi.2020.10.009  

34.Skopec M, Issa H, Reed J, Harris M. The role of geographic bias 

in knowledge diffusion: a systematic review and narrative synthesis. 

Res Integr Peer Rev. 2020;5:2. DOI:10.1186/s41073-019-0088-0  

35.Mulimani P. Publication bias towards Western populations 

harms humanity. Nat Hum Behav. 2019;3(10):1026-7. 

DOI:10.1038/s41562-019-0720-5 

36.Marques R, Lopes M, Ramos P, Neves Amado J, Alves P. 

Prognostic factors for delayed healing of complex wounds in adults: 

A scoping review protocol. Nurs Rep. 2022;12(4):904-11. 

DOI:10.3390/nursrep12040087  

37.Bekele F, Chelkeba L. Amputation rate of diabetic foot ulcer and 

associated factors in diabetes mellitus patients admitted to 

Nekemte referral hospital, western Ethiopia: Prospective 

observational study. J Foot Ankle Res. 2020;13(1):65. 

DOI:10.1186/s13047-020-00433-9  

38.Jenkins DA, Mohamed S, Taylor JK, Peek N, van der Veer SN. 

Potential prognostic factors for delayed healing of common, non-

traumatic skin ulcers: A scoping review. Int Wound J. 

2019;16(3):800-12. DOI:10.1111/iwj.13100  

39.Leanne M. Kmet, Robert C. Lee, Cook LS. Standardquality 

assessment criteria for evaluating primary research papers from a 

variety of fields [Internet]. AHFMR. 2014; [cited 2024, July 5]. 

Available from: 

https://www.ihe.ca/download/standard_quality_assessment_criteri

a_for_evaluating_primary_research_papers_from_a_variety_of_fi

elds.pdf 

40.JBI levels of evidence [Internet]. Joanna Briggs Institute. 2013; 

[cited 2024, July 5]. Available from: 

https://jbi.global/sites/default/files/2019-05/JBI-Levels-of-

evidence_2014_0.pdf 

41.Williams-Reid H. Data for: Wound Management, Healing, and 

Early Prosthetic Rehabilitation: A Scoping Review of Biomarkers 

[Internet]. University of Strathclyde KnowledgeBase; 2024. [cited 

2024, Jul 5]. Available from: https://doi.org/10.15129/f5044ee8-

5689-49c2-a67a-1cbe26af8a58 

42.Chen CY, Wu RW, Hsu MC, Hsieh CJ, Chou MC. Adjunctive 

hyperbaric oxygen therapy for healing of chronic diabetic foot 

ulcers: A randomized controlled trial. J Wound Ostomy Continence 

Nurs. 2017;44(6):536-45. DOI:10.1097/won.0000000000000374  

43.Dinoto E, Ferlito F, La Marca MA, Tortomasi G, Urso F, Evola S, 

et al. The role of early revascularization and biomarkers in the 

management of diabetic foot ulcers: A single center experience. 

Diagnostics (Basel). 2022;12(2). DOI:10.3390/ 

diagnostics12020538 

44.Hansen RL, Langdahl BL, Jørgensen PH, Petersen KK, Søballe 

K, Stilling M. Changes in periprosthetic bone mineral density and 

bone turnover markers after osseointegrated implant surgery: A 

cohort study of 20 transfemoral amputees with 30-month follow-up. 

Prosthet Orthot Int. 2019;43(5):508-18. DOI:10.1177/ 

0309364619866599 

45.Kevin L, Jagadeesh M, Priscilla L, Kacie K, Richard S, Edwin R, 

et al. Oxygenation based perfusion assessment of diabetic foot 

ulcers using a breath-hold paradigm. ProcSPIE. 2019;10873: 

1087304. DOI:10.1117/12.2509917 

https://doi.org/10.33137/cpoj.v7i2.43716
https://www.prisma-statement.org/scoping
https://www.prisma-statement.org/scoping
https://www.ihe.ca/download/standard_quality_assessment_criteria_for_evaluating_primary_research_papers_from_a_variety_of_fields.pdf
https://www.ihe.ca/download/standard_quality_assessment_criteria_for_evaluating_primary_research_papers_from_a_variety_of_fields.pdf
https://www.ihe.ca/download/standard_quality_assessment_criteria_for_evaluating_primary_research_papers_from_a_variety_of_fields.pdf
https://jbi.global/sites/default/files/2019-05/JBI-Levels-of-evidence_2014_0.pdf
https://jbi.global/sites/default/files/2019-05/JBI-Levels-of-evidence_2014_0.pdf
https://doi.org/10.15129/f5044ee8-5689-49c2-a67a-1cbe26af8a58
https://doi.org/10.15129/f5044ee8-5689-49c2-a67a-1cbe26af8a58


 

14 

Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 2 - A scoping review of physical biomarkers. 
Canadian Prosthetics & Orthotics Journal. 2024; Volume 7, Issue 2, No.3. https://doi.org/10.33137/cpoj.v7i2.43716 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X WOUND MANAGEMENT: PHYSICAL BIOMARKERS 

Williams-Reid et al., 2024 

46. Kimura T, Watanabe Y, Tokuoka S, Nagashima F, Ebisudani S, 

Inagawa K. Utility of skin perfusion pressure values with the society 

for vascular surgery wound, ischemia, and foot infection 

classification system. J Vasc Surg. 2019;70(4):1308-17. 

DOI:10.1016/j.jvs.2019.01.045 

47. Lin DS, Lee JK. Mobile Health-Based Thermometer for 

monitoring wound healing after endovascular therapy in patients 

with chronic foot ulcer: Prospective cohort study. JMIR Mhealth 

Uhealth. 2021;9(5):e26468. DOI:10.2196/26468  

48.Strauss C, Anker A, Klein S, Kemper R, Brebant V, Prantl L, et 

al. Monitoring free flaps and replanted digits via perfusion index - A 

proof of concept study. Clin Hemorheol Microcirc. 2022;80(4):363-

71. DOI:10.3233/ch-211295 

49.Ariyanti AD, Zhang J, Marcelina O, Nugrahaningrum DA, Wang 

G, Kasim V, et al. Salidroside-pretreated mesenchymal stem cells 

enhance diabetic wound healing by promoting paracrine function 

and survival of mesenchymal stem cells under hyperglycemia. 

Stem Cells Transl Med. 2019;8(4):404-14. DOI:10.1002/sctm.18-

0143 

50.Begum F, Manandhar S, Kumar G, Keni R, Sankhe R, Gurram 

PC, et al. Dehydrozingerone promotes healing of diabetic foot 

ulcers: A molecular insight. J Cell Commun Signal. 2023;17(3):673-

88. DOI:10.1007/s12079-022-00703-0  

51.Bian J, Bao L, Gao X, Wen X, Zhang Q, Huang J, et al. Bacteria-

engineered porous sponge for hemostasis and vascularization. J 

Nanobiotechnology. 2022;20(1):47. DOI:10.1186/s12951-022-

01254-7 

52.Bibi S, Ahmad F, Alam MR, Ansar M, Yeou KS, Wahedi HM. 

lapachol-induced upregulation of sirt1/sirt3 is linked with improved 

skin wound healing in alloxan-induced diabetic mice. Iran J Pharm 

Res. 2021;20(3):419-30. DOI:10.22037/ijpr.2021.112722.13914 

53.Chen J, Bao X, Meng T, Sun J, Yang X. Zeolitic imidazolate 

framework-67 accelerates infected diabetic chronic wound healing. 

Chem Eng J. 2022;430:133091. DOI:10.1016/j.cej.2021.133091 

54.Chen L, Ma W, Covassin N, Chen D, Zha P, Wang C, et al. 

Association of sleep-disordered breathing and wound healing in 

patients with diabetic foot ulcers. J Clin Sleep Med. 2021;17(5):909-

16. DOI:10.5664/jcsm.9088 

55.Chowdary AR, Maerz T, Henn D, Hankenson KD, Pagani CA, 

Marini S, et al. Macrophage-mediated PDGF activation correlates 

with regenerative outcomes following musculoskeletal trauma. Ann 

Surg. 2023;278(2):e349-e59. DOI:10.1097/sla.0000000000005704 

56.Derakhshandeh H, Aghabaglou F, McCarthy A, Mostafavi A, 

Wiseman C, Bonick Z, et al. A wirelessly controlled smart bandage 

with 3d-printed miniaturized needle arrays. Adv Funct Mater. 

2020;30(13). DOI:10.1002/adfm.201905544 

57.Ding Y, Cui L, Zhao Q, Zhang W, Sun H, Zheng L. Platelet-rich 

fibrin accelerates skin wound healing in diabetic mice. Ann Plast 

Surg. 2017;79(3):e15-e9. DOI:10.1097/sap.0000000000001091 

58.Doulamis A, Doulamis N, Angeli A, Lazaris A, Luthman S, 

Jayapala M, et al. A non-invasive photonics-based device for 

monitoring of diabetic foot ulcers: Architectural/sensorial 

components & technical specifications. Inventions. 2021;6(2):27. 

59.El-Gizawy SA, Nouh A, Saber S, Kira AY. Deferoxamine-loaded 

transfersomes accelerates healing of pressure ulcers in 

streptozotocin-induced diabetic rats. J Drug Deliv Sci Technol. 

2020;58:101732. DOI:10.1016/j.jddst.2020.101732 

60.Elliott CG, Wang J, Walker JT, Michelsons S, Dunmore-Buyze 

J, Drangova M, et al. Periostin and CCN2 scaffolds promote the 

wound healing response in the skin of diabetic mice. Tissue Eng 

Part A. 2019;25(17-18):1326-39. DOI:10.1089/ten.TEA.2018.0268  

61.Escuin-Ordinas H, Liu Y, Sun L, Hugo W, Dimatteo R, Huang 

RR, et al. Wound healing with topical BRAF inhibitor therapy in a 

diabetic model suggests tissue regenerative effects. PLoS One. 

2021;16(6):e0252597. DOI:10.1371/journal.pone.0252597  

62.Friedman A, Siewe N. Mathematical model of chronic dermal 

wounds in diabetes and obesity. Bull Math Biol. 2020;82(10):137. 

DOI:10.1007/s11538-020-00815-x  

63.Gao R, Zhou P, Li Y, Li Q. High glucose-induced IL-7/IL-7R 

upregulation of dermal fibroblasts inhibits angiogenesis in a 

paracrine way in delayed diabetic wound healing. J Cell Commun 

Signal. 2023;17(3):1023-38. DOI:10.1007/s12079-023-00754-x  

64.Gao S, Chen T, Wang Z, Ji P, Xu L, Cui W, et al. Immuno-

activated mesenchymal stem cell living electrospun nanofibers for 

promoting diabetic wound repair. J Nanobiotechnology. 

2022;20(1):294. DOI:10.1186/s12951-022-01503-9  

65.Greene CJ, Anderson S, Barthels D, Howlader MSI, Kanji S, 

Sarkar J, et al. DPSC products accelerate wound healing in diabetic 

mice through induction of SMAD molecules. Cells. 2022;11(15). 

DOI:10.3390/cells11152409 

66.Hassan RF, Kadhim HM. Comparative effects of phenolic extract 

as an ointment dosage form in inducing wound healing in mice and 

β-sitosterol in experimentally induced acute wound healing in mice. 

J Pharm Negat Results. 2022;13(3):194-203. DOI:10.47750/ 

pnr.2022.13.03.031 

67.He FL, Qiu S, Zou JL, Gu FB, Yao Z, Tu ZH, et al. Covering the 

proximal nerve stump with chondroitin sulfate proteoglycans 

prevents traumatic painful neuroma formation by blocking axon 

regeneration after neurotomy in Sprague Dawley rats. J Neurosurg. 

2021;134(5):1599-609. DOI:10.3171/2020.3.Jns193202 

68.He S, Walimbe T, Chen H, Gao K, Kumar P, Wei Y, et al. 

Bioactive extracellular matrix scaffolds engineered with 

proangiogenic proteoglycan mimetics and loaded with endothelial 

progenitor cells promote neovascularization and diabetic wound 

healing. Bioact Mater. 2022;10:460-73. DOI:10.1016/ 

j.bioactmat.2021.08.017 

69.Huon JF, Gaborit B, Caillon J, Boutoille D, Navas D. A murine 

model of Staphylococcus aureus infected chronic diabetic wound: 

A new tool to develop alternative therapeutics. Wound Repair 

Regen. 2020;28(3):400-8. DOI:10.1111/wrr.12802 

70.Husakova J, Bem R, Fejfarova V, Jirkovska A, Woskova V, 

Jarosikova R, et al. Factors influencing the risk of major amputation 

in patients with diabetic foot ulcers treated by autologous cell 

therapy. J Diabetes Res. 2022;2022:3954740. DOI:10.1155/ 

2022/3954740 

71.Ji X, Jin P, Yu P, Wang P. Autophagy ameliorates Pseudomonas 

aeruginosa-infected diabetic wounds by regulating the toll-like 

https://doi.org/10.33137/cpoj.v7i2.43716


 

15 

Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 2 - A scoping review of physical biomarkers. 
Canadian Prosthetics & Orthotics Journal. 2024; Volume 7, Issue 2, No.3. https://doi.org/10.33137/cpoj.v7i2.43716 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X WOUND MANAGEMENT: PHYSICAL BIOMARKERS 

Williams-Reid et al., 2024 

receptor 4/myeloid differentiation factor 88 pathway. Wound Repair 

Regen. 2023;31(3):305-20. DOI:10.1111/wrr.13074  

72.Jing S, Li H, Xu H. Mesenchymal stem cell derived exosomes 

therapy in diabetic wound repair. Int J Nanomedicine. 

2023;18:2707-20. DOI:10.2147/ijn.S411562 

73.Kanji S, Das M, Joseph M, Aggarwal R, Sharma SM, Ostrowski 

M, et al. Nanofiber-expanded human CD34(+) cells heal cutaneous 

wounds in streptozotocin-induced diabetic mice. Sci Rep. 

2019;9(1):8415. DOI:10.1038/s41598-019-44932-7 

74.Kasowanjete P, Abrahamse H, Houreld NN. Photobiomodulation 

at 660 nm stimulates in vitro diabetic wound healing via the 

Ras/MAPK pathway. Cells. 2023;12(7). DOI:10.3390/ 

cells12071080 

75.Khan MS, Tauqeer Ahmed M. Novel candidates for chronic 

diabetic wound healing. J Pak Assoc Dermatol. 2022;32(3):526-31. 

76.Kim BE, Goleva E, Hall CF, Park SH, Lee UH, Brauweiler AM, 

et al. Skin wound healing is accelerated by a lipid mixture 

representing major lipid components of chamaecyparis obtusa 

plant extract. J Invest Dermatol. 2018;138(5):1176-86. 

DOI:10.1016/j.jid.2017.11.039 

77.Kim S, Piao J, Hwang DY, Park JS, Son Y, Hong HS. Substance 

P accelerates wound repair by promoting neovascularization and 

preventing inflammation in an ischemia mouse model. Life Sci. 

2019;225:98-106. DOI:10.1016/j.lfs.2019.04.015 

78.Kolumam G, Wu X, Lee WP, Hackney JA, Zavala-Solorio J, 

Gandham V, et al. IL-22R ligands IL-20, IL-22, and IL-24 promote 

wound healing in diabetic db/db Mice. PLoS One. 

2017;12(1):e0170639 DOI:10.1371/journal.pone.0170639 

79.Kurkipuro J, Mierau I, Wirth T, Samaranayake H, Smith W, 

Kärkkäinen HR, et al. Four in one-combination therapy using live 

lactococcus lactis expressing three therapeutic proteins for the 

treatment of chronic non-healing wounds. PLoS One. 

2022;17(2):e0264775. DOI:10.1371/journal.pone.0264775 

80.Lee Y-H, Lin S-J. Chitosan/PVA Hetero-composite hydrogel 

containing antimicrobials, perfluorocarbon nanoemulsions, and 

growth factor-loaded nanoparticles as a multifunctional dressing for 

diabetic wound healing: synthesis, characterization, and in vitro/in 

vivo evaluation. Pharmaceutics. 2022;14(3):537.  

81.Lee YH, Hong YL, Wu TL. Novel silver and nanoparticle-

encapsulated growth factor co-loaded chitosan composite hydrogel 

with sustained antimicrobility and promoted biological properties for 

diabetic wound healing. Mater Sci Eng C Mater Biol Appl. 

2021;118:111385. DOI:10.1016/j.msec.2020.111385  

82.Leu JG, Chiang MH, Chen CY, Lin JT, Chen HM, Chen YL, et al. 

Adenine accelerated the diabetic wound healing by PPAR delta and 

angiogenic regulation. Eur J Pharmacol. 2018;818:569-77. 

DOI:10.1016/j.ejphar.2017.11.027  

83.Li B, Zhou Y, Chen J, Wang T, Li Z, Fu Y, et al. Long non-coding 

RNA H19 contributes to wound healing of diabetic foot ulcer. J Mol 

Endocrinol. 2020. DOI:10.1530/jme-19-0242  

84.Li C, Liu SY, Zhou LP, Min TT, Zhang M, Pi W, et al. 

Polydopamine-modified chitin conduits with sustained release of 

bioactive peptides enhance peripheral nerve regeneration in rats. 

Neural Regen Res. 2022;17(11):2544-50. DOI:10.4103/1673-

5374.339006  

85.Li G, Li D, Wu C, Li S, Chen F, Li P, et al. Homocysteine-targeting 

compounds as a new treatment strategy for diabetic wounds via 

inhibition of the histone methyltransferase SET7/9. Exp Mol Med. 

2022;54(7):988-98. DOI:10.1038/s12276-022-00804-1 

86.Li J, Chou H, Li L, Li H, Cui Z. Wound healing activity of neferine 

in experimental diabetic rats through the inhibition of inflammatory 

cytokines and nrf-2 pathway. Artif Cells Nanomed Biotechnol. 

2020;48(1):96-106. DOI:10.1080/21691401.2019. 1699814 

87.Li M, Li X, Gao Y, Yang Y, Yi C, Huang W, et al. Composite 

nanofibrous dressing loaded with Prussian blue and heparin for 

anti-inflammation therapy and diabetic wound healing. Int J Biol 

Macromol. 2023;242(Pt 3):125144. DOI:10.1016/j.ijbiomac.2023. 

125144 

88.Li S, Wang X, Chen J, Guo J, Yuan M, Wan G, et al. Calcium ion 

cross-linked sodium alginate hydrogels containing deferoxamine 

and copper nanoparticles for diabetic wound healing. Int J Biol 

Macromol. 2022;202:657-70. DOI:10.1016/j.ijbiomac.2022.01.080  

89.Li X, Xie X, Lian W, Shi R, Han S, Zhang H, et al. Exosomes 

from adipose-derived stem cells overexpressing Nrf2 accelerate 

cutaneous wound healing by promoting vascularization in a diabetic 

foot ulcer rat model. Exp Mol Med. 2018;50(4):1-14. 

DOI:10.1038/s12276-018-0058-5 

90.Liu C, Teo MHY, Pek SLT, Wu X, Leong ML, Tay HM, et al. A 

multifunctional role of leucine-rich α-2-glycoprotein 1 in cutaneous 

wound healing under normal and diabetic conditions. Diabetes. 

2020;69(11):2467-80. DOI:10.2337/db20-0585 

91.Liu Y, Zhang X, Yang L, Zhou S, Li Y, Shen Y, et al. Proteomics 

and transcriptomics explore the effect of mixture of herbal extract 

on diabetic wound healing process. Phytomedicine. 

2023;116:154892. DOI:10.1016/j.phymed.2023.154892 

92.Luan H, Huiru g, Mo Z, Ren W, Guo H, Chu Z, et al. The bone 

alterations in hind limb amputation rats in vivo. Med Nov Technol 

Devices. 2020;8:100046. DOI:10.1016/j.medntd.2020.100046 

93.Manso G, Elias-Oliveira J, Guimarães JB, Pereira Í S, Rodrigues 

VF, Burger B, et al. Xenogeneic mesenchymal stem cell biocurative 

improves skin wounds healing in diabetic mice by increasing mast 

cells and the regenerative profile. Regen Ther. 2023;22:79-89. 

DOI:10.1016/j.reth.2022.12.006 

94.McLaughlin PJ, Cain JD, Titunick MB, Sassani JW, Zagon IS. 

Topical naltrexone is a safe and effective alternative to standard 

treatment of diabetic wounds. Adv Wound Care (New Rochelle). 

2017;6(9):279-88. DOI:10.1089/wound.2016.0725 

95.Mehrvar S, Rymut KT, Foomani FH, Mostaghimi S, Eells JT, 

Ranji M, et al. Fluorescence imaging of mitochondrial redox state 

to assess diabetic wounds. IEEE J Transl Eng Health Med. 

2019;7:1800809. DOI:10.1109/jtehm.2019.2945323  

96.Mokoena DR, Houreld NN, Dhilip Kumar SS, Abrahamse H. 

Photobiomodulation at 660 nm stimulates fibroblast differentiation. 

Lasers Surg Med. 2020;52(7):671-81. DOI:10.1002/lsm.23204 

97.Mutlu HS, Erdoğan A, Tapul L. Autologously transplanted dermal 

fibroblasts improved diabetic wound in rat model. Acta 

https://doi.org/10.33137/cpoj.v7i2.43716


 

16 

Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 2 - A scoping review of physical biomarkers. 
Canadian Prosthetics & Orthotics Journal. 2024; Volume 7, Issue 2, No.3. https://doi.org/10.33137/cpoj.v7i2.43716 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X WOUND MANAGEMENT: PHYSICAL BIOMARKERS 

Williams-Reid et al., 2024 

Histochemica. 2020;122(5):151552. DOI:10.1016/j.acthis.2020. 

151552  

98.Nasrullah MZ. Caffeic acid phenethyl ester loaded PEG-PLGA 

nanoparticles enhance wound healing in diabetic rats. Antioxidants 

(Basel). 2022;12(1). DOI:10.3390/antiox12010060  

99.Nishikai-Yan Shen T, Kado M, Hagiwara H, Fujimura S, Mizuno 

H, Tanaka R. MMP9 secreted from mononuclear cell quality and 

quantity culture mediates STAT3 phosphorylation and fibroblast 

migration in wounds. Regen Ther. 2021;18:464-71. 

DOI:10.1016/j.reth.2021.10.003 

100.Paul TS, Das BB, Talekar YP, Banerjee S. Exploration of the 

role of a lithophytic fern, Pteris vittata L. in wound tissue 

regeneration and remodelling of genes in hyperglycaemic rat 

model. Clinical Phytoscience. 2020;6(1):79. DOI:10.1186/s40816-

020-00223-7 

101.Ridiandries A, Bursill C, Tan J. Broad-spectrum inhibition of the 

cc-chemokine class improves wound healing and wound 

angiogenesis. Int J Mol Sci. 2017;18(1). DOI:10.3390/ 

ijms18010155 

102.Senturk B, Demircan BM, Ozkan AD, Tohumeken S, Delibasi 

T, Guler MO, et al. Diabetic wound regeneration using heparin-

mimetic peptide amphiphile gel in db/db mice. Biomater Sci. 

2017;5(7):1293-303. DOI:10.1039/c7bm00251c  

103.Silva JC, Pitta MGR, Pitta IR, Koh TJ, Abdalla DSP. New 

peroxisome proliferator-activated receptor agonist (GQ-11) 

improves wound healing in diabetic mice. Adv Wound Care (New 

Rochelle). 2019;8(9):417-28. DOI:10.1089/wound.2018.0911  

104.Spreadborough PJ, Strong AL, Mares J, Levi B, Davis TA. 

Tourniquet use following blast-associated complex lower limb injury 

and traumatic amputation promotes end organ dysfunction and 

amplified heterotopic ossification formation. J Orthop Surg Res. 

2022;17(1):422. DOI:10.1186/s13018-022-03321-z  

105.Strong AL, Spreadborough PJ, Dey D, Yang P, Li S, Lee A, et 

al. BMP Ligand Trap ALK3-Fc Attenuates osteogenesis and 

heterotopic ossification in blast-related lower extremity trauma. 

Stem Cells Dev. 2021;30(2):91-105. DOI:10.1089/scd.2020.0162  

106.Sun X, Wang X, Zhao Z, Chen J, Li C, Zhao G. Paeoniflorin 

accelerates foot wound healing in diabetic rats though activating 

the Nrf2 pathway. Acta Histochemica. 2020;122(8):151649. 

DOI:10.1016/j.acthis.2020.151649  

107.Tan SS, Yeo XY, Liang ZC, Sethi SK, Tay SSW. Stromal 

vascular fraction promotes fibroblast migration and cellular viability 

in a hyperglycemic microenvironment through up-regulation of 

wound healing cytokines. Exp Mol Pathol. 2018;104(3):250-5. 

DOI:10.1016/j.yexmp.2018.03.007  

108.Tan WS, Arulselvan P, Ng SF, Mat Taib CN, Sarian MN, 

Fakurazi S. Improvement of diabetic wound healing by topical 

application of Vicenin-2 hydrocolloid film on Sprague Dawley rats. 

BMC Complement Altern Med. 2019;19(1):20. 

DOI:10.1186/s12906-018-2427-y 

109.Tellechea A, Bai S, Dangwal S, Theocharidis G, Nagai M, 

Koerner S, et al. Topical application of a mast cell stabilizer 

improves impaired diabetic wound healing. J Invest Dermatol. 

2020;140(4):901-11.e11. DOI:10.1016/j.jid.2019.08.449 

110.Tkaczyk C, Jones-Nelson O, Shi YY, Tabor DE, Cheng L, 

Zhang T, et al. Neutralizing staphylococcus aureus virulence with 

AZD6389, a three mab combination, accelerates closure of a 

diabetic polymicrobial wound. mSphere. 2022;7(3):e0013022. 

DOI:10.1128/msphere.00130-22 

111.Wang H, Wang X, Liu X, Zhou J, Yang Q, Chai B, et al. miR-

199a-5p Plays a pivotal role on wound healing via suppressing 

vegfa and rock1 in diabetic ulcer foot. Oxid Med Cell Longev. 

2022;2022:4791059. DOI:10.1155/2022/4791059 

112.Wang T, Zheng Y, Shi Y, Zhao L. pH-responsive calcium 

alginate hydrogel laden with protamine nanoparticles and 

hyaluronan oligosaccharide promotes diabetic wound healing by 

enhancing angiogenesis and antibacterial activity. Drug Deliv 

Transl Res. 2019;9(1):227-39. DOI:10.1007/s13346-018-00609-8 

113.Wu T, Xie D, Zhao X, Xu M, Luo L, Deng D, et al. Enhanced 

expression of miR-34c in peripheral plasma associated with 

diabetic foot ulcer in type 2 diabetes patients. Diabetes Metab 

Syndr Obes. 2021;14:4263-73. DOI:10.2147/dmso.S326066 

114.Xia G, Liu Y, Tian M, Gao P, Bao Z, Bai X, et al. 

Nanoparticles/thermosensitive hydrogel reinforced with chitin 

whiskers as a wound dressing for treating chronic wounds. J Mater 

Chem B. 2017;5(17):3172-85. DOI:10.1039/c7tb00479f 

115.Xiang X, Chen J, Jiang T, Yan C, Kang Y, Zhang M, et al. Milk-

derived exosomes carrying siRNA-KEAP1 promote diabetic wound 

healing by improving oxidative stress. Drug Deliv Transl Res. 

2023;13(9):2286-96. DOI:10.1007/s13346-023-01306-x 

 116.Yadav S, Arya DK, Pandey P, Anand S, Gautam AK, Ranjan S, 

et al. ECM mimicking biodegradable nanofibrous scaffold enriched 

with Curcumin/ZnO to accelerate diabetic wound healing via 

multifunctional bioactivity. Int J Nanomedicine. 2022;17:6843-59. 

DOI:10.2147/ijn.S388264 

117.Yan J, Tie G, Wang S, Tutto A, DeMarco N, Khair L, et al. 

Diabetes impairs wound healing by Dnmt1-dependent 

dysregulation of hematopoietic stem cells differentiation towards 

macrophages. Nat Commun. 2018;9(1):33. DOI:10.1038/s41467-

017-02425-z 

118.Yang Y, Hu H, Wang W, Duan X, Luo S, Wang X, et al. The 

identification of functional proteins from amputated lumbricus 

Eisenia fetida on the wound healing process. Biomed 

Pharmacother. 2017;95:1469-78. DOI:10.1016/j.biopha.2017.09. 

049 

119.Ye J, Kang Y, Sun X, Ni P, Wu M, Lu S. MicroRNA-155 inhibition 

promoted wound healing in diabetic rats. Int J Low Extrem Wounds. 

2017;16(2):74-84. DOI:10.1177/1534734617706636 

120.Zahid AA, Ahmed R, Ur Rehman SR, Augustine R, Hasan A. 

Reactive nitrogen species releasing hydrogel for enhanced wound 

healing. Annu Int Conf IEEE Eng Med Biol Soc. 2019;2019:3939-

42. DOI:10.1109/embc.2019.8856469 

121.Zhang F, Liu Y, Wang S, Yan X, Lin Y, Chen D, et al. Interleukin-

25-mediated-IL-17RB upregulation promotes cutaneous wound 

healing in diabetic mice by improving endothelial cell functions. 

Front Immunol. 2022;13:809755. DOI:10.3389/fimmu.2022.809755 

122.Zhang Y, Jiang W, Kong L, Fu J, Zhang Q, Liu H. PLGA@IL-8 

nanoparticles-loaded acellular dermal matrix as a delivery system 

https://doi.org/10.33137/cpoj.v7i2.43716


 

17 

Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 2 - A scoping review of physical biomarkers. 
Canadian Prosthetics & Orthotics Journal. 2024; Volume 7, Issue 2, No.3. https://doi.org/10.33137/cpoj.v7i2.43716 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X WOUND MANAGEMENT: PHYSICAL BIOMARKERS 

Williams-Reid et al., 2024 

for exogenous MSCs in diabetic wound healing. Int J Biol 

Macromol. 2023;224:688-98. DOI:10.1016/j.ijbiomac.2022.10.157 

123.Zhao Y, Luo L, Huang L, Zhang Y, Tong M, Pan H, et al. In situ 

hydrogel capturing nitric oxide microbubbles accelerates the 

healing of diabetic foot. J Control Release. 2022;350:93-106. 

DOI:10.1016/j.jconrel.2022.08.018 

124.Zhao Y, Wang X, Yang S, Song X, Sun N, Chen C, et al. 

Kanglexin accelerates diabetic wound healing by promoting 

angiogenesis via FGFR1/ERK signaling. Biomed Pharmacother. 

2020;132:110933. DOI:10.1016/j.biopha.2020.110933 

125.Zheng Z, Liu Y, Yang Y, Tang J, Cheng B. Topical 1% 

propranolol cream promotes cutaneous wound healing in 

spontaneously diabetic mice. Wound Repair Regen. 

2017;25(3):389-97. DOI:10.1111/wrr.12546 

126.Zhu Z, Wang L, Peng Y, Xiaoying C, Zhou L, Jin Y, et al. 

Continuous self‐oxygenated double‐layered hydrogel under natural 

light for real‐time infection monitoring, enhanced photodynamic 

therapy, and hypoxia relief in refractory diabetic wounds healing. 

Adv Funct Mater. 2022;32. DOI:10.1002/adfm.202201875 

127.Nensat C, Songjang W, Tohtong R, Suthiphongchai T, Phimsen 

S, Rattanasinganchan P, et al. Porcine placenta extract improves 

high-glucose-induced angiogenesis impairment. BMC Complement 

Med Ther. 2021;21(1):66. DOI:10.1186/s12906-021-03243-z 

128.Zhang S, Wang S, Xu L, He Y, Xiang J, Tang Z. Clinical 

outcomes of transmetatarsal amputation in patients with diabetic 

foot ulcers treated without revascularization. Diabetes Ther. 

2019;10(4):1465-72. DOI:10.1007/s13300-019-0653-z 

129.Yang X, Mathis BJ, Huang Y, Li W, Shi Y. KLF4 Promotes 

diabetic chronic wound healing by suppressing Th17 cell 

differentiation in an MDSC-dependent manner. J Diabetes Res. 

2021;2021:7945117. DOI:10.1155/2021/7945117 

130.Yang S, Gu Z, Lu C, Zhang T, Guo X, Xue G, et al. Neutrophil 

extracellular traps are markers of wound healing impairment in 

patients with diabetic foot ulcers treated in a multidisciplinary 

setting. Adv Wound Care (New Rochelle). 2020;9(1):16-27. 

DOI:10.1089/wound.2019.0943 

131.Wu M, Yu Z, Matar DY, Karvar M, Chen Z, Ng B, et al. Human 

amniotic membrane promotes angiogenesis in an oxidative stress 

chronic diabetic murine wound model. Adv Wound Care (New 

Rochelle). 2023;12(6):301-15. DOI:10.1089/wound.2022.0005 

132.Woo Y, Suh YJ, Lee H, Jeong E, Park SC, Yun SS, et al. TcPO2 

value can predict wound healing time in clinical practice of CLTI 

patients. Ann Vasc Surg. 2023;91:249-56. DOI:10.1016/j.avsg. 

2022.11.020 

133.Vieceli Dalla Sega F, Cimaglia P, Manfrini M, Fortini F, 

Marracino L, Bernucci D, et al. Circulating biomarkers of endothelial 

dysfunction and inflammation in predicting clinical outcomes in 

diabetic patients with critical limb ischemia. Int J Mol Sci. 

2022;23(18). DOI:10.3390/ijms231810641 

134.Vatankhah N, Jahangiri Y, Landry GJ, McLafferty RB, Alkayed 

NJ, Moneta GL, et al. Predictive value of neutrophil-to-lymphocyte 

ratio in diabetic wound healing. J Vasc Surg. 2017;65(2):478-83. 

DOI:10.1016/j.jvs.2016.08.108 

135.Vangaveti VN, Jhamb S, Hayes O, Goodall J, Bulbrook J, 

Robertson K, et al. Effects of vildagliptin on wound healing and 

markers of inflammation in patients with type 2 diabetic foot ulcer: 

a prospective, randomized, double-blind, placebo-controlled, 

single-center study. Diabetol Metab Syndr. 2022;14(1):183. 

DOI:10.1186/s13098-022-00938-2  

136.Tanaka K, Tanaka S, Okazaki J, Mii S. Preoperative nutritional 

status is independently associated with wound healing in patients 

undergoing open surgery for ischemic tissue loss. Vascular. 

2021;29(6):897-904. DOI:10.1177/1708538120980216 

137.Squiers JJ, Thatcher JE, Bastawros DS, Applewhite AJ, Baxter 

RD, Yi F, et al. Machine learning analysis of multispectral imaging 

and clinical risk factors to predict amputation wound healing. J Vasc 

Surg. 2022;75(1):279-85. DOI:10.1016/j.jvs.2021.06.478 

138.Shi L, Xue J, Zhao W, Wei X, Zhang M, Li L, et al. The 

prognosis of diabetic foot ulcer is independent of age? a 

comparative analysis of the characteristics of patients with diabetic 

foot ulcer in different age groups: A cross-sectional study from 

China. Int J Low Extrem Wounds. 2022:15347346221125844. 

DOI:10.1177/15347346221125844 

139.Salaun P, Desormais I, Lapébie FX, Rivière AB, Aboyans V, 

Lacroix P, et al. Comparison of ankle pressure, systolic toe 

pressure, and transcutaneous oxygen pressure to predict major 

amputation after 1 year in the COPART Cohort. Angiology. 

2019;70(3):229-36. DOI:10.1177/0003319718793566 

140.Razjouyan J, Grewal GS, Talal TK, Armstrong DG, Mills JL, 

Najafi B. Does physiological stress slow down wound healing in 

patients with diabetes? J Diabetes Sci Technol. 2017;11(4):685-92. 

DOI:10.1177/1932296817705397 

141.Rajagopalan C, Viswanathan V, Rajsekar S, Selvaraj B, Daniel 

L. Diabetic foot ulcers—comparison of performance of ankle-

brachial index and transcutaneous partial oxygen pressure in 

predicting outcome. Int J Diabetes Dev Ctries. 2018;38(2):179-84. 

DOI:10.1007/s13410-017-0580-3 

142.Pan X, You C, Chen G, Shao H, Han C, Zhi L. Skin perfusion 

pressure for the prediction of wound healing in critical limb 

ischemia: A meta-analysis. Arch Med Sci. 2018;14(3):481-7. 

DOI:10.5114/aoms.2016.62220 

143.Ou S, Xu C, Yang Y, Chen Y, Li W, Lu H, et al. Transverse tibial 

bone transport enhances distraction osteogenesis and 

vascularization in the treatment of diabetic foot. Orthop Surg. 

2022;14(9):2170-9. DOI:10.1111/os.13416 

144.Nystrom LM, Mesko NW, Jin Y, Shah C, Spiguel A, White J, et 

al. Transcutaneous oximetry does not reliably predict wound-

healing complications in preoperatively radiated soft tissue 

sarcoma. Clin Orthop Relat Res. 2023;481(3):542-9. 

DOI:10.1097/corr.0000000000002279 

145.Norvell DC, Czerniecki JM. Risks and risk factors for ipsilateral 

re-amputation in the first year following first major unilateral 

dysvascular amputation. Eur J Vasc Endovasc Surg. 

2020;60(4):614-21. DOI:10.1016/j.ejvs.2020.06.026 

146.Nayak M, Nag HL, Nag TC, Digge V, Yadav R. Ultrastructural 

and histological changes in tibial remnant of ruptured anterior 

cruciate ligament stumps: a transmission electron microscopy and 

https://doi.org/10.33137/cpoj.v7i2.43716


 

18 

Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 2 - A scoping review of physical biomarkers. 
Canadian Prosthetics & Orthotics Journal. 2024; Volume 7, Issue 2, No.3. https://doi.org/10.33137/cpoj.v7i2.43716 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X WOUND MANAGEMENT: PHYSICAL BIOMARKERS 

Williams-Reid et al., 2024 

immunochemistry-based observational study. Musculoskelet Surg. 

2020;104(1):67-74. DOI:10.1007/s12306-019-00599-x  

147.Moon KC, Kim SB, Han SK, Jeong SH, Dhong ES. Risk factors 

for major amputation in hospitalized diabetic patients with forefoot 

ulcers. Diabetes Res Clin Pract. 2019;158:107905. 

DOI:10.1016/j.diabres.2019.107905 

148.Moon KC, Kim KB, Han SK, Jeong SH, Dhong ES. Risk factors 

for major amputation on hindfoot ulcers in hospitalized diabetic 

patients. Adv Wound Care (New Rochelle). 2019;8(5):177-85. 

DOI:10.1089/wound.2018.0814 

149.Modaghegh MHS, Saberianpour S, Amoueian S, Shahri JJ, 

Rahimi H. The effect of redox signaling on extracellular matrix 

changes in diabetic wounds leading to amputation. Biochem 

Biophys Rep. 2021;26:101025. DOI:10.1016/j.bbrep.2021.101025 

150.Metcalf DG, Haalboom M, Bowler PG, Gamerith C, Sigl E, 

Heinzle A, et al. Elevated wound fluid pH correlates with increased 

risk of wound infection. Wound Med. 2019;26(1):100166. 

DOI:10.1016/j.wndm.2019.100166. 

151.Mendoza-Marí Y, García-Ojalvo A, Fernández-Mayola M, 

Rodríguez-Rodríguez N, Martinez-Jimenez I, Berlanga-Acosta J. 

Epidermal growth factor effect on lipopolysaccharide-induced 

inflammation in fibroblasts derived from diabetic foot ulcer. Scars 

Burn Heal. 2022;8:20595131211067380. DOI:10.1177/ 

20595131211067380  

152.Majumdar M, Lella S, Hall RP, Sumetsky N, Waller HD, 

McElroy I, et al. Utilization of thromboelastography with platelet 

mapping to predict infection and poor wound healing in 

postoperative vascular patients. Ann Vasc Surg. 2022;87:213-24. 

DOI:10.1016/j.avsg.2022.03.008 

153.Lin BS, Chang CC, Tseng YH, Li JR, Peng YS, Huang YK. 

Using wireless near-infrared spectroscopy to predict wound 

prognosis in diabetic foot ulcers. Adv Skin Wound Care. 

2020;33(1):1-12. DOI:10.1097/01.ASW.0000613552.50065.d5 

154.Li J, Arora S, Ikeoka K, Smith J, Dash S, Kimura S, et al. The 

utility of geriatric nutritional risk index to predict outcomes in chronic 

limb-threatening ischemia. Catheter Cardiovasc Interv. 

2022;99(1):121-33. DOI:10.1002/ccd.29949 

155.Lee YJ, Ahn CM, Ko YG, Park KH, Lee JW, Lee SJ, et al. Skin 

perfusion pressure predicts early wound healing after endovascular 

therapy in chronic limb threatening ischaemia. Eur J Vasc 

Endovasc Surg. 2021;62(6):909-17. DOI: 

10.1016/j.ejvs.2021.08.030 

156. Lee JV, Engel C, Tay S, DeSilva G, Desai K, Cashin J, et al. 

Impact of N-acetyl-cysteine on ischemic stumps following major 

lower extremity amputation: a pilot randomized clinical trial. Ann 

Surg. 2022;276(5):e302-e10. DOI:10.1097/sla.0000000000005389 

157.Koyama A, Kodama A, Tsuruoka T, Fujii T, Sugimoto M, Banno 

H, et al. Zinc deficiency and clinical outcome after infrainguinal 

bypass grafting for critical limb ischemia. Circ Rep. 2020;2(3):167-

73. DOI:10.1253/circrep.CR-20-0003 

158.Kodama A, Komori K, Koyama A, Sato T, Ikeda S, Tsuruoka T, 

et al. Impact of serum zinc level and oral zinc supplementation on 

clinical outcomes in patients undergoing infrainguinal bypass for 

chronic limb-threatening ischemia. Circ J. 2022;86(6):995-1006. 

DOI:10.1253/circj.CJ-21-0832 

159.Kim KG, Mishu M, Zolper EG, Bhardwaj P, Rogers A, Dekker 

PK, et al. Nutritional markers for predicting lower extremity free 

tissue transfer outcomes in the chronic wound population. 

Microsurgery. 2023;43(1):51-6. DOI:10.1002/micr.30794 

160.Kee KK, Nair HKR, Yuen NP. Risk factor analysis on the 

healing time and infection rate of diabetic foot ulcers in a referral 

wound care clinic. J Wound Care. 2019;28(Sup1):S4-s13. 

DOI:10.12968/jowc.2019.28.Sup1.S4  

161.Katagiri T, Kondo K, Shibata R, Hayashida R, Shintani S, 

Yamaguchi S, et al. Therapeutic angiogenesis using autologous 

adipose-derived regenerative cells in patients with critical limb 

ischaemia in Japan: A clinical pilot study. Sci Rep. 

2020;10(1):16045. DOI:10.1038/s41598-020-73096-y 

162.Junaidi F, Muradi A, Pratama D, Suhartono R, Kekalih A. 

Effectiveness of doppler ultrasonography as a predictor of wound 

healing after below-knee amputation for peripheral arterial disease. 

Chirurgia (Bucur). 2020;115(5):618-25. DOI:10.21614/chirurgia. 

115.5.618  

163.Jeon BJ, Choi HJ, Kang JS, Tak MS, Park ES. Comparison of 

five systems of classification of diabetic foot ulcers and predictive 

factors for amputation. Int Wound J. 2017;14(3):537-45. 

DOI:10.1111/iwj.12642 

164.Hata Y, Iida O, Okamoto S, Ishihara T, Nanto K, Tsujumura T, 

et al. Additional risk stratification using local and systemic factors 

for patients with critical limb ischaemia undergoing endovascular 

therapy in the Wi-Fi era. Eur J Vasc Endovasc Surg. 

2019;58(4):548-55. DOI:10.1016/j.ejvs.2019.06.005  

165.Guo Z, Yue C, Qian Q, He H, Mo Z. Factors associated with 

lower-extremity amputation in patients with diabetic foot ulcers in a 

Chinese tertiary care hospital. Int Wound J. 2019;16(6):1304-13. 

DOI:10.1111/iwj.13190  

166.Gülcü A, Etli M, Karahan O, Aslan A. Analysis of routine blood 

markers for predicting amputation/re-amputation risk in diabetic 

foot. Int Wound J. 2020;17(6):1996-2004. DOI:10.1111/iwj.13491  

167.Giesen LJ, van den Boom AL, van Rossem CC, den Hoed PT, 

Wijnhoven BP. Retrospective multicenter study on risk factors for 

surgical site infections after appendectomy for acute appendicitis. 

Dig Surg. 2017;34(2):103-7. DOI:10.1159/000447647  

168.Gazzaruso C, Gallotti P, Pujia A, Montalcini T, Giustina A, 

Coppola A. Predictors of healing, ulcer recurrence and persistence, 

amputation and mortality in type 2 diabetic patients with diabetic 

foot: a 10-year retrospective cohort study. Endocrine. 

2021;71(1):59-68. DOI:10.1007/s12020-020-02431-0  

169.Gao C, Yang L, Ju J, Gao Y, Zhang K, Wu M, et al. Risk and 

prognostic factors of replantation failure in patients with severe 

traumatic major limb mutilation. Eur J Trauma Emerg Surg. 

2022;48(4):3203-10. DOI:10.1007/s00068-021-01876-w 

170.Furuyama T, Yamashita S, Yoshiya K, Kurose S, Yoshino S, 

Nakayama K, et al. The controlling nutritional status score is 

significantly associated with complete ulcer healing in patients with 

critical limb ischemia. Ann Vasc Surg. 2020;66:510-7. 

DOI:10.1016/j.avsg.2019.12.031 

171.Furuyama T, Onohara T, Yamashita S, Yoshiga R, Yoshiya K, 

Inoue K, et al. Prognostic factors of ulcer healing and amputation-

https://doi.org/10.33137/cpoj.v7i2.43716


 

19 

Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 2 - A scoping review of physical biomarkers. 
Canadian Prosthetics & Orthotics Journal. 2024; Volume 7, Issue 2, No.3. https://doi.org/10.33137/cpoj.v7i2.43716 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X WOUND MANAGEMENT: PHYSICAL BIOMARKERS 

Williams-Reid et al., 2024 

free survival in patients with critical limb ischemia. Vascular. 

2018;26(6):626-33. DOI:10.1177/1708538118786864 

172.Ferroni L, Gardin C, De Pieri A, Sambataro M, Seganfreddo E, 

Goretti C, et al. Treatment of diabetic foot ulcers with Therapeutic 

Magnetic Resonance (TMR®) improves the quality of granulation 

tissue. Eur J Histochem. 2017;61(3):2800. DOI:10.4081/ejh. 

2017.2800  

173.Dutra LMA, Melo MC, Moura MC, Leme LAP, De Carvalho MR, 

Mascarenhas AN, et al. Prognosis of the outcome of severe 

diabetic foot ulcers with multidisciplinary care. J Multidiscip Healthc. 

2019;12:349-59. DOI:10.2147/jmdh.S194969  

174.Das SK, Yuan YF, Li MQ. Predictors of delayed wound healing 

after successful isolated below-the-knee endovascular intervention 

in patients with ischemic foot ulcers. J Vasc Surg. 2018;67(4):1181-

90. DOI:10.1016/j.jvs.2017.08.077  

175.Cheng P, Dong Y, Hu Z, Huang S, Cao X, Wang P, et al. 

Biomarker prediction of postoperative healing of diabetic foot 

ulcers: A retrospective observational study of serum albumin. 

Journal of Wound Ostomy & Continence Nursing. 2021;48(4):339-

44. DOI:10.1097/won.0000000000000780  

176.Chaudhary N, Huda F, Roshan R, Basu S, Rajput D, Singh SK. 

Lower limb amputation rates in patients with diabetes and an 

infected foot ulcer: A prospective observational study. Wound 

Manag Prev. 2021;67(7):22-30.  

177.Chan AS, Montbriand J, Eisenberg N, Roche-Nagle G. 

Outcomes of minor amputations in patients with peripheral vascular 

disease over a 10-year period at a tertiary care institution. Vascular. 

2019;27(1):8-18. DOI:10.1177/1708538118797544  

178.Campitiello F, Mancone M, Cammarota M, D'Agostino A, Ricci 

G, Stellavato A, et al. Acellular dermal matrix used in diabetic foot 

ulcers: Clinical outcomes supported by biochemical and histological 

analyses. Int J Mol Sci. 2021;22(13). DOI:10.3390/ijms22137085  

179.Bramley JL, Worsley PR, Bostan LE, Bader DL, Dickinson AS. 

Establishing a measurement array to assess tissue tolerance 

during loading representative of prosthetic use. Med Eng Phys. 

2020;78:39-47. DOI:10.1016/j.medengphy.2020.01.011  

180.Berli MC, Wanivenhaus F, Kabelitz M, Götschi T, Böni T, Rancic 

Z, et al. Predictors for reoperation after lower limb amputation in 

patients with peripheral arterial disease. Vasa. 2019;48(5):419-24. 

DOI:10.1024/0301-1526/a000796  

181.Barć P, Antkiewicz M, Śliwa B, Baczyńska D, Witkiewicz W, 

Skóra JP. Treatment of critical limb ischemia by 

pIRES/VEGF165/HGF administration. Ann Vasc Surg. 

2019;60:346-54. DOI:10.1016/j.avsg.2019.03.013 

182.Anguiano-Hernandez YM, Contreras-Mendez L, de Los 

Angeles Hernandez-Cueto M, Muand Oz-Medina JE, Santillan-

Verde MA, Barbosa-Cabrera RE, et al. Modification of HIF-1α, NF-

aκB, IGFBP-3, VEGF and adiponectin in diabetic foot ulcers treated 

with hyperbaric oxygen. Undersea Hyperb Med. 2019;46(1):35-44. 

183.Aljarrah Q, Allouh MZ, Husein A, Al-Jarrah H, Hallak A, Bakkar 

S, et al. Transmetatarsal amputations in patients with diabetes 

mellitus: A contemporary analysis from an academic tertiary referral 

centre in a developing community. PLoS One. 

2022;17(11):e0277117. DOI:10.1371/journal.pone.0277117  

184.Alfawaz A, Kotha VS, Nigam M, Bekeny JC, Black CK, Tefera 

E, et al. Popliteal artery patency is an indicator of ambulation and 

healing after below-knee amputation in vasculopaths. Vascular. 

2022;30(4):708-14. DOI:10.1177/17085381211026498  

185.Ahn J, Raspovic KM, Liu GT, Lavery LA, La Fontaine J, 

Nakonezny PA, et al. Renal function as a predictor of early 

transmetatarsal amputation failure. Foot Ankle Spec. 

2019;12(5):439-51. DOI:10.1177/1938640018816371  

186.Aguirre A, Sharma K, Arora A, Humphries MD. Early ABI testing 

may decrease risk of amputation for patients with lower extremity 

ulcers. Ann Vasc Surg. 2022;79:65-71. DOI:10.1016/j.avsg. 

2021.08.015  

187.Adams BE, Edlinger JP, Ritterman Weintraub ML, Pollard JD. 

Three-year morbidity and mortality rates after nontraumatic 

transmetatarsal amputation. J Foot Ankle Surg. 2018;57(5):967-71. 

DOI:10.1053/j.jfas.2018.03.047  

188.Zubair M, Ahmad J. Transcutaneous oxygen pressure 

(TcPO(2)) and ulcer outcome in diabetic patients: Is there any 

correlation? Diabetes Metab Syndr. 2019;13(2):953-8. 

DOI:10.1016/j.dsx.2018.12.008  

189.Yang AE, Hartranft CA, Reiss A, Holden CR. Improving 

outcomes for lower extremity amputations using intraoperative 

fluorescent angiography to predict flap viability. Vasc Endovascular 

Surg. 2018;52(1):16-21. DOI:10.1177/1538574417740048  

190.Trejo J, Ryan E, Khan F, Iannuzzi N, Chansky H, Lack WD. 

Risk factors for failure of limb salvage among veterans with foot 

ulcers. Foot Ankle Surg. 2022;28(5):584-7. DOI:10.1016/j.fas. 

2021.06.003 

191.Ramaprabha P, Ramani CP, Kesavan R. Study on microbiome 

of chronic non healing diabetic ulcers with special reference to 

biofilm and multidrug resistant strains. J Clin Diagn Res. 2021. 

DOI:10.7860/JCDR/2021/50126.15471 

192. Pu D, Lei X, Leng W, Zheng Y, Chen L, Liang Z, et al. Lower 

limb arterial intervention or autologous platelet-rich gel treatment of 

diabetic lower extremity arterial disease patients with foot ulcers. 

Ann Transl Med. 2019;7(18):485. DOI:10.21037/atm.2019.07.87  

193.Nur Rosyid F, Dharmana E, Suwondo A, Hs K, Sugiarto S. The 

effect of bitter melon (Momordica Charantia L.) leaves extract on 

TNF-α serum levels and diabetic foot ulcers improvement: 

Randomized controlled trial. Biomed Pharmacol J. 2018;11:1413-

21. DOI:10.13005/bpj/1505  

194.Nolan GS, Smith OJ, Heavey S, Jell G, Mosahebi A. 

Histological analysis of fat grafting with platelet-rich plasma for 

diabetic foot ulcers-A randomised controlled trial. Int Wound J. 

2022;19(2):389-98. DOI:10.1111/iwj.13640 

195.Morisaki K, Yamaoka T, Iwasa K. Risk factors for wound 

complications and 30-day mortality after major lower limb 

amputations in patients with peripheral arterial disease. Vascular. 

2018;26(1):12-7. DOI:10.1177/1708538117714197  

196.Chiang N, Rodda OA, Sleigh J, Vasudevan T. Effects of topical 

negative pressure therapy on tissue oxygenation and wound 

healing in vascular foot wounds. J Vasc Surg. 2017;66(2):564-71. 

DOI:10.1016/j.jvs.2017.02.050  

https://doi.org/10.33137/cpoj.v7i2.43716


 

20 

Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 2 - A scoping review of physical biomarkers. 
Canadian Prosthetics & Orthotics Journal. 2024; Volume 7, Issue 2, No.3. https://doi.org/10.33137/cpoj.v7i2.43716 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X WOUND MANAGEMENT: PHYSICAL BIOMARKERS 

Williams-Reid et al., 2024 

197.Chen Z, Haus JM, DiPietro LA, Koh TJ, Minshall RD. 

Neutralization of excessive CCL28 improves wound healing in 

diabetic mice. Front Pharmacol. 2023;14:1087924. 

DOI:10.3389/fphar.2023.1087924 

198.Van Den Hoven P, Van Den Berg SD, Van Der Valk JP, Van Der 

Krogt H, Van Doorn LP, Van De Bogt KEA, et al. Assessment of 

tissue viability following amputation surgery using near-infrared 

fluorescence imaging with indocyanine green. Ann Vasc Surg. 

2022;78:281-7. DOI:10.1016/j.avsg.2021.04.030  

199.Nayak M, Nag HL, Nag TC, Yadav R, Singh V, Maredupaka S. 

Ultrastructural characterization of cells in the tibial stump of 

ruptured human anterior cruciate ligament, their changes and 

significance with duration of injury. Med Mol Morphol. 

2020;53(2):86-93. DOI:10.1007/s00795-019-00233-6 

200.Gurina TS, Simms L. Histology, Staining. [Updated 2023 May 

1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls 

Publishing; [cited 2024, July 5]. Available from: 

https://www.ncbi.nlm.nih.gov/books/NBK557663/ 

201.Leonard AK, Loughran EA, Klymenko Y, Liu Y, Kim O, Asem M, 

et al. Methods for the visualization and analysis of extracellular 

matrix protein structure and degradation. Methods Cell Biol. 

2018;143:79-95. DOI:10.1016/bs.mcb.2017.08.005 

202.Mathew-Steiner SS, Roy S, Sen CK. Collagen in wound 

healing. Bioengineering (Basel). 2021;8(5). 

DOI:10.3390/bioengineering8050063  

203.Rao RS, Patil S, Majumdar B, Oswal RG. Comparison of 

special stains for keratin with routine hematoxylin and eosin stain. 

J Int Oral Health. 2015;7(3):1-5. 

204.Pastar I, Stojadinovic O, Yin NC, Ramirez H, Nusbaum AG, 

Sawaya A, et al. Epithelialization in wound healing: A 

comprehensive review. Adv Wound Care (New Rochelle). 

2014;3(7):445-64. DOI:10.1089/wound.2013.0473 

205.Explaining your kidney test results: A tool for clinical use 

[Internet]. National Institute of Health (N.I.H.). 2012; [cited 2024, 

July 5]. Available from: https://www.niddk.nih.gov/health-

information/professionals/advanced-search/explain-kidney-test-

results#:~:text=GFR%20%2D%20A%20blood%20test%20measur

es,in%20the%20kidneys%20are%20damaged 

206.Kumar M, Dev S, Khalid MU, Siddenthi SM, Noman M, John 

C, et al. The bidirectional link between diabetes and kidney disease: 

mechanisms and management. Cureus. 2023;15(9):e45615. 

DOI:10.7759/cureus.45615 

207.Maroz N, Simman R. Wound healing in patients with impaired 

kidney function. J Am Coll Clin Wound Spec. 2013;5(1):2-7. 

DOI:10.1016/j.jccw.2014.05.002 

208.Seth AK, De la Garza M, Fang RC, Hong SJ, Galiano RD. 

Excisional wound healing is delayed in a murine model of chronic 

kidney disease. PLoS One. 2013;8(3):e59979. 

DOI:10.1371/journal.pone.0059979 

209.Castilla DM, Liu ZJ, Velazquez OC. Oxygen: Implications for 

wound healing. Adv Wound Care (New Rochelle). 2012;1(6):225-

30. DOI:10.1089/wound.2011.0319 

 

210.Kimmel HM, Grant A, Ditata J. The presence of oxygen in 

wound healing. Wounds. 2016;28(8):264-70.  

211.Yip WL. Influence of oxygen on wound healing. Int Wound J. 

2015;12(6):620-4. DOI:10.1111/iwj.12324.  

212.Loo AE, Halliwell B. Effects of hydrogen peroxide in a 

keratinocyte-fibroblast co-culture model of wound healing. Biochem 

Biophys Res Commun. 2012;423(2):253-8. 

DOI:10.1016/j.bbrc.2012.05.100 

213.Kmiec MM, Hou H, Lakshmi Kuppusamy M, Drews TM, 

Prabhat AM, Petryakov SV, et al. Transcutaneous oxygen 

measurement in humans using a paramagnetic skin adhesive film. 

Magn Reson Med. 2019;81(2):781-94. DOI:10.1002/mrm.27445 

214.Catella J, Long A, Mazzolai L. What is currently the role of 

tcpo2 in the choice of the amputation level of lower limbs? A 

comprehensive review. J Clin Med. 2021;10(7). 

DOI:10.3390/jcm10071413 

215.Mesquida J, Gruartmoner G, Espinal C. Skeletal muscle 

oxygen saturation (StO2) measured by near-infrared spectroscopy 

in the critically ill patients. Biomed Res Int. 2013;2013:502194. 

DOI:10.1155/2013/502194 

216.Lee LL, Chen SL. Assessment of hyperspectral imaging in 

pressure injury healing. Adv Skin Wound Care. 2022;35(8):429-34. 

DOI:10.1097/01.ASW.0000831888.39420.a6  

217.Graser M, Day S, Buis A. Exploring the role of transtibial 

prosthetic use in deep tissue injury development: A scoping review. 

BMC Biomed Eng. 2020;2:2. DOI:10.1186/s42490-020-0036-6  

218.Li WW, Carter MJ, Mashiach E, Guthrie SD. Vascular 

assessment of wound healing: A clinical review. Int Wound J. 

2017;14(3):460-9. DOI:10.1111/iwj.12622 

219.DiPietro LA. Angiogenesis and wound repair: When enough is 

enough. J Leukoc Biol. 2016;100(5):979-84. 

DOI:10.1189/jlb.4MR0316-102R 

220.Brownrigg JR, Hinchliffe RJ, Apelqvist J, Boyko EJ, Fitridge R, 

Mills JL, et al. Performance of prognostic markers in the prediction 

of wound healing or amputation among patients with foot ulcers in 

diabetes: A systematic review. Diabetes Metab Res Rev. 2016;32 

Suppl 1:128-35. DOI:10.1002/dmrr.2704 

221.Grizzle WE. Issues in the use of human tissues to support 

precision medicine. J Health Care Poor Underserved. 

2019;30(4s):66-78. DOI:10.1353/hpu.2019.0117 

222.McClary KN, Massey P. Ankle Brachial Index. [Updated 2023 

Jan 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls 

Publishing. 2024; [cited 2024, July 5]. Available from: 

https://www.ncbi.nlm.nih.gov/books/NBK544226/ 

223.Diagnosis; Peripheral arterial disease (PAD) [Internet]. NHS. 

2023; [cited 2024, July 5]. Available from: 

https://www.nhs.uk/conditions/peripheral-arterial-disease-

pad/diagnosis/ 

224.Duval S, Keo HH, Oldenburg NC, Baumgartner I, Jaff MR, 

Peacock JM, et al. The impact of prolonged lower limb ischemia on 

amputation, mortality, and functional status: the FRIENDS registry. 

Am Heart J. 2014;168(4):577-87. DOI:10.1016/j.ahj.2014.06.013 

https://doi.org/10.33137/cpoj.v7i2.43716
https://www.ncbi.nlm.nih.gov/books/NBK557663/
https://www.niddk.nih.gov/health-information/professionals/advanced-search/explain-kidney-test-results#:~:text=GFR%20%2D%20A%20blood%20test%20measures,in%20the%20kidneys%20are%20damaged
https://www.niddk.nih.gov/health-information/professionals/advanced-search/explain-kidney-test-results#:~:text=GFR%20%2D%20A%20blood%20test%20measures,in%20the%20kidneys%20are%20damaged
https://www.niddk.nih.gov/health-information/professionals/advanced-search/explain-kidney-test-results#:~:text=GFR%20%2D%20A%20blood%20test%20measures,in%20the%20kidneys%20are%20damaged
https://www.niddk.nih.gov/health-information/professionals/advanced-search/explain-kidney-test-results#:~:text=GFR%20%2D%20A%20blood%20test%20measures,in%20the%20kidneys%20are%20damaged
https://www.ncbi.nlm.nih.gov/books/NBK544226/
https://www.nhs.uk/conditions/peripheral-arterial-disease-pad/diagnosis/
https://www.nhs.uk/conditions/peripheral-arterial-disease-pad/diagnosis/


 

21 

Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 2 - A scoping review of physical biomarkers. 
Canadian Prosthetics & Orthotics Journal. 2024; Volume 7, Issue 2, No.3. https://doi.org/10.33137/cpoj.v7i2.43716 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X WOUND MANAGEMENT: PHYSICAL BIOMARKERS 

Williams-Reid et al., 2024 

225.Madsen UR, Hyldig N, Juel K. Outcomes in patients with 

chronic leg wounds in Denmark: A nationwide register-based cohort 

study. Int Wound J. 2022;19(1):156-68. DOI:10.1111/iwj.13607 

226.DeMeulenaere S. Pulse Oximetry: Uses and limitations. J. 

Nurse Pract. 2007;3(5):312-7. DOI:10.1016/j.nurpra.2007.02.021 

227.Ochoa M, Rahimi R, Zhou J, Jiang H, Yoon CK, Maddipatla D, 

et al. Integrated sensing and delivery of oxygen for next-generation 

smart wound dressings. Microsyst. Nanoeng. 2020;6(1):46. 

DOI:10.1038/s41378-020-0141-7  

228.Swaminathan A, Vemulapalli S, Patel MR, Jones WS. Lower 

extremity amputation in peripheral artery disease: Improving patient 

outcomes. Vasc Health Risk Manag. 2014;10:417-24. 

DOI:10.2147/vhrm.S50588 

229.Collaborators GD. Global, regional, and national burden of 

diabetes from 1990 to 2021, with projections of prevalence to 2050: 

A systematic analysis for the global burden of disease study 2021. 

Lancet. 2023;402(10397):203-34. DOI:10.1016/s0140-

6736(23)01301-6   

230.Oliver TI, Mutluoglu M. Diabetic Foot Ulcer [Internet]. In: 

StatPearls. Treasure Island, Florida: StatPearls Publishing. [cited 

2024, July 5]. Available from:  

https://www.ncbi.nlm.nih.gov/books/NBK537328/ 

231.Lin C, Liu J, Sun H. Risk factors for lower extremity amputation 

in patients with diabetic foot ulcers: A meta-analysis. PLoS One. 

2020;15(9):e0239236. DOI:10.1371/journal.pone.0239236  

232.Lu Q, Wang J, Wei X, Wang G, Xu Y. Risk factors for major 

amputation in diabetic foot ulcer patients. Diabetes Metab Syndr 

Obes. 2021;14:2019-27. DOI:10.2147/dmso.S307815   

233.Carr R, Hebenton J, Davie-Smith F. A survey of the lower limb 

amputee population in Scotland 2019 public report [Internet]. 
Scottish Physiotherapy Amputee Research Group 2022; [cited 

2024, July 5]. Available from: 

https://www.bacpar.org/data/Resource_Downloads/SPARGReport

2019(Public).pdf 

234.Yazdanyar A, Newman AB. The burden of cardiovascular 

disease in the elderly: Morbidity, mortality, and costs. Clin Geriatr 

Med. 2009;25(4):563-77, vii. DOI:10.1016/j.cger.2009.07.007 

235.Van Langevelde K, Srámek A, Rosendaal FR. The effect of 

aging on venous valves. Arterioscler Thromb Vasc Biol. 

2010;30(10):2075-80. DOI:10.1161/atvbaha.110.209049   

236.Margolis DJ, Knauss J, Bilker W, Baumgarten M. Medical 

conditions as risk factors for pressure ulcers in an outpatient 

setting. Age Ageing. 2003;32(3):259-64. DOI:10.1093/ 

ageing/32.3.259  

237.England PH. Diabetes Prevalence Model [Internet]. London. 

2016; [cited 2024, July 5]. Available from: 

https://assets.publishing.service.gov.uk/media/5a82c07340f0b623

0269c82d/Diabetesprevalencemodelbriefing.pdf 

238.Tas U, Verhagen AP, Bierma-Zeinstra SM, Odding E, Koes BW. 

Prognostic factors of disability in older people: A systematic review. 

Br J Gen Pract. 2007;57(537):319-23 

239.Khalid KA, Nawi AFM, Zulkifli N, Barkat MA, Hadi H. Aging and 

wound healing of the skin: A review of clinical and 

pathophysiological hallmarks. Life (Basel). 2022;12(12). 

DOI:10.3390/life12122142 

240.Zhang H, Huang C, Bai J, Wang J. Effect of diabetic foot ulcers 

and other risk factors on the prevalence of lower extremity 

amputation: A meta-analysis. Int Wound J. 2023;20(8):3035-47. 

DOI:10.1111/iwj.14179  

241.Vanherwegen AS, Lauwers P, Lavens A, Doggen K, Dirinck E. 

Sex differences in diabetic foot ulcer severity and outcome in 

Belgium. PLoS One. 2023;18(2):e0281886. DOI:10.1371/journal. 

pone.0281886  

242.Offner PJ, Moore EE, Biffl WL. Male gender is a risk factor for 

major infections after surgery. Arch Surg. 1999;134(9):935-8; 

discussion 8-40. DOI:10.1001/archsurg.134.9.935  

243.Pape M, Giannakópoulos GF, Zuidema WP, de Lange-Klerk 

ESM, Toor EJ, Edwards MJR, et al. Is there an association between 

female gender and outcome in severe trauma? A multi-center 

analysis in the Netherlands. Scand J Trauma Resusc Emerg Med. 

2019;27(1):16. DOI:10.1186/s13049-019-0589-3  

244.Singh R, Hunter J, Philip A, Tyson S. Gender differences in 

amputation outcome. Disabil Rehabil. 2008;30(2):122-5. 

DOI:10.1080/09638280701254095  

245.Use of both sexes to be default in laboratory experimental 

design [Internet]. UK Research and Innovation (UKRI). 2022;  [cited 

2024, July 5]. Available from: https://www.ukri.org/news/use-of-

both-sexes-to-be-default-in-laboratory-experimental-

design/#:~:text=Making%20both%20sexes%20the%20default&tex

t=Both%20sexes%20should%20be%20used,of%20any%20increa

se%20in%20costs 

246.Fahrenkopf MP, Adams NS, Kelpin JP, Do VH. Hand 

amputations. Eplasty. 2018;18:ic21.  

247.Johnson BZ, Stevenson AW, Prêle CM, Fear MW, Wood FM. 

The role of IL-6 in skin fibrosis and cutaneous wound healing. 

Biomedicines. 2020;8(5). DOI:10.3390/biomedicines8050101  

248.Lindley LE, Stojadinovic O, Pastar I, Tomic-Canic M. Biology 

and biomarkers for wound healing. Plast Reconstr Surg. 

2016;138(3 Suppl):18s-28s. DOI:10.1097/prs.0000000000002682  

249.Bracken MB. Why animal studies are often poor predictors of 

human reactions to exposure. J R Soc Med. 2009;102(3):120-2. 

DOI:10.1258/jrsm.2008.08k033  

250.Afzal A, Saleel CA, Bhattacharyya S, Satish N, Samuel OD, 

Badruddin IA. Merits and limitations of mathematical modeling and 

computational simulations in mitigation of COVID-19 pandemic: A 

comprehensive review. Arch Comput Methods Eng. 

2022;29(2):1311-37. DOI:10.1007/s11831-021-09634-2   

251.White A, Tolman M, Thames HD, Withers HR, Mason KA, 

Transtrum MK. The limitations of model-based experimental design 

and parameter estimation in sloppy systems. PLoS Comput Biol. 

2016;12(12):e1005227. DOI:10.1371/journal.pcbi.1005227  

252.Menon SN, Flegg JA. Mathematical modeling can advance 

wound healing research. Adv Wound Care (New Rochelle). 

2021;10(6):328-44. DOI:10.1089/wound.2019.1132 

 253.Hong WX, Hu MS, Esquivel M, Liang GY, Rennert RC, 

McArdle A, et al. The role of hypoxia-inducible factor in wound 

https://doi.org/10.33137/cpoj.v7i2.43716
https://www.ncbi.nlm.nih.gov/books/NBK537328/
https://www.bacpar.org/data/Resource_Downloads/SPARGReport2019(Public).pdf
https://www.bacpar.org/data/Resource_Downloads/SPARGReport2019(Public).pdf
https://assets.publishing.service.gov.uk/media/5a82c07340f0b6230269c82d/Diabetesprevalencemodelbriefing.pdf
https://assets.publishing.service.gov.uk/media/5a82c07340f0b6230269c82d/Diabetesprevalencemodelbriefing.pdf
https://www.ukri.org/news/use-of-both-sexes-to-be-default-in-laboratory-experimental-design/#:~:text=Making%20both%20sexes%20the%20default&text=Both%20sexes%20should%20be%20used,of%20any%20increase%20in%20costs
https://www.ukri.org/news/use-of-both-sexes-to-be-default-in-laboratory-experimental-design/#:~:text=Making%20both%20sexes%20the%20default&text=Both%20sexes%20should%20be%20used,of%20any%20increase%20in%20costs
https://www.ukri.org/news/use-of-both-sexes-to-be-default-in-laboratory-experimental-design/#:~:text=Making%20both%20sexes%20the%20default&text=Both%20sexes%20should%20be%20used,of%20any%20increase%20in%20costs
https://www.ukri.org/news/use-of-both-sexes-to-be-default-in-laboratory-experimental-design/#:~:text=Making%20both%20sexes%20the%20default&text=Both%20sexes%20should%20be%20used,of%20any%20increase%20in%20costs
https://www.ukri.org/news/use-of-both-sexes-to-be-default-in-laboratory-experimental-design/#:~:text=Making%20both%20sexes%20the%20default&text=Both%20sexes%20should%20be%20used,of%20any%20increase%20in%20costs


 

22 

Williams-Reid H, Johannesson A, Buis A. Wound management, healing, and early prosthetic rehabilitation: Part 2 - A scoping review of physical biomarkers. 
Canadian Prosthetics & Orthotics Journal. 2024; Volume 7, Issue 2, No.3. https://doi.org/10.33137/cpoj.v7i2.43716 

CANADIAN PROSTHETICS & ORTHOTICS JOURNAL 

ISSN: 2561-987X WOUND MANAGEMENT: PHYSICAL BIOMARKERS 

Williams-Reid et al., 2024 

healing. Adv Wound Care (New Rochelle). 2014;3(5):390-9. 

DOI:10.1089/wound.2013.0520  

254.Gazendam AM, Slawaska-Eng D, Nucci N, Bhatt O, Ghert M. 

The impact of industry funding on randomized controlled trials of 

biologic therapies. Medicines (Basel). 2022;9(3). 

DOI:10.3390/medicines9030018 

255.Canêo LF, Neirotti R. The importance of the proper definition of 

adulthood: What is and what is not included in a scientific 

publication. Braz J Cardiovasc Surg. 2017;32(1):60. 

DOI:10.21470/1678-9741-2016-0049 

256.Paez A. Gray literature: An important resource in systematic 

reviews. J Evid Based Med. 2017;10(3):233-40. 

DOI:10.1111/jebm.12266 

 

Abbreviations & Acronyms: 

 

Abbreviations 

& Acronyms 
Definition 

ABI Ankle-Brachial Index 

C.G. Control Groups 

CKD Chronic Kidney Disease 

DBP Diastolic Blood Pressure 

DFUs Diabetic Foot Ulcers 

eGFR Estimated Glomerular Filtration Rate 

U.S. FDA  United States Food & Drug Administration 

H&E Haematoxylin and Eosin 

H2O2 Hydrogen Peroxide 

JBI Joanna Briggs Institute 

MTT Assay 
3-[4,5-Dimethylthiazol-2-yl]-2,5-Diphenyltetrazolium 

Bromide Assay 

NHS National Health Service 

No. Number 

PAD Peripheral Arterial Disease 

PRISMA-ScR 
Preferred Reporting Items for Systematic Review 

and Meta-Analyses for Scoping Reviews 

ROS Reactive Oxygen Species 

SBP Systolic Blood Pressure 

SpO2 Saturation of Peripheral Oxygen 

SPP Skin Perfusion Pressure 

StO2 Skeletal Muscle Oxygen Saturation 

T.G. Treatment Groups 

TcPO2 Transcutaneous Oximetry 

UK United Kingdom 

USA United States of America 

VRO Vessel Run-Off 

 
 
 

https://doi.org/10.33137/cpoj.v7i2.43716

