Dermatology: Practical and Conceptual Review | Dermatol Pract Concept. 2025;15(2):4945 1 Omega-3 Acellular Fish Skin Grafts for Chronic and Complicated Wounds: A Systematic Review of Efficacy and Safety Sonali Karhana1, Mohd. Ashif Khan1 1 Department of Translational & Clinical Research, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, India Key words: Acellular fish skin graft, Biopsy wounds, Diabetic foot ulcer, Wound healing, Wound therapy Citation: Karhana S, Khan MA. Omega-3 Acellular Fish Skin Grafts for Chronic and Complicated Wounds: A Systematic Review of Efficacy and Safety. Dermatol Pract Concept. 2025;15(2):4945. DOI: https://DOI.org/10.5826/dpc.1502a4945 Accepted: November 26, 2024; Published: April 2025 Copyright: ©2025 Karhana et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Dr. Mohd Ashif Khan, Department of Translational & Clinical Research, School of Chemical and Life Sciences Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India. ORCID ID:0000-0003-1576-8779. Email: mhdashifkhan@gmail.com, makhan@jamiahamdard.ac.in Introduction: A systematic review was conducted to investigate the efficacy of acellular fish skin grafts (AFSGs) for the treatment of complicated wounds. AFSGs can be used as a regenerative and antimicrobial tool for healing complicated wounds, but clinical evidence remains unclear. Objective: This systematic review aimed to summarize the efficacy of AFSGs on complicated wounds using evidence from existing published studies. Methods: Electronic databases like PubMed, ScienceDirect, Google Scholar, and Clinicaltrials.gov were searched for relevant literature reporting on the efficacy of AFSGs for wound healing. Based on the inclusion and exclusion criteria, nine studies were selected for data extraction. The quality of the articles was evaluated using the RoB 2 and ROBINS-I tools. Results: Existing evidence shows that AFSGs accelerate wound healing, reduce pain, prevent antibiot- ic administration, and cause no autoimmune reactions. The total re-epithelialization time for diabetic foot ulcers (DFUs) was observed as 15 ± 8 weeks, depending on the severity of the ulcers. Acute full thickness biopsy wounds healed within 3.75 ± 0.25 weeks. As reported in papers, AFSGs showed sig- nificantly better effects than standard-of-care therapy, collagen alginate dressings, dehydrated human AMNION/chorion membrane, and/ or porcine small-intestine submucosa. However, instances of rash- es, erythema, pain, and hypergranulation were reported when AFSGs were applied to biopsy wounds. Conclusion: Overall, the evidence obtained in this systematic review indicates that AFSGs represent a clinically and financially effective option for the treatment of wounds when compared with conven- tional alternatives. ABSTRACT 2 Review | Dermatol Pract Concept. 2025;15(2):4945 Introduction Wounds are identified as a break or separation from the continuity of skin or tissue caused by physical, biological or chemical factors [1]. The economic, social, and clinical impact of wounds is on the rise, and novel strategies for wound management and treatment are needed. The global wound care market is growing at a compound annual growth rate (CAGR) of 6.6% (period 2020–2027) and is estimated to reach USD 18.7 billion by 2027 [2]. The hard- to-heal wounds frequently encountered in wound care prac- tice include diabetic foot ulcers (DFUs), venous leg ulcers (VLUs), post-surgical wounds, and wound dehiscence. DFU is a chronic wound, with its market expected to reach USD 11.05 billion by 2027 [3]. Despite recent developments, the incidence of DFUs has not decreased in the last two decades [3]. DFU is the leading cause of hospitalization among dia- betic patients, accounting for 25% of hospital admissions [4]. Moreover, 14%-24% of foot ulcer patients have to un- dergo amputations [5]. In addition, the global market of ve- nous ulcers is estimated to reach USD 4.8 billion, growing at a CAGR of 6.4% (2019-2026) [6]. Another problem that has remained to be dealt with in the last several decades is that of wound dehiscence. Post-laparotomy wound dehis- cence occurs in approximately 0.25% to 3% of patients who undergo the procedure, necessitating immediate surgical in- tervention, with a mortality rate of 20% [7]. Additionally, traumatic wounds, surgical wounds, and superficial burns or abrasions are classified as acute wounds. Acute biopsy wounds are also prevalent among patients, in which case in- adequate treatment of such acute wounds leads to the forma- tion of chronic wounds [8]. Apart from the financial impact, hard-to-heal wounds impose a significant degradation in pa- tients’ quality of life. Several treatment strategies have been introduced that promote wound healing by accelerating the healing process at a molecular level [9-11]. Existing topical agents include iodine solutions, hypochlorous acid, cadex- omer iodine, and collagenase [12,13]. Similarly, several types of dressings are now available, like acrylics, honey alginates, alginates, micronized collagen, hydrocolloids, hydrofibers, and oxidized regenerated cellulose [14]. These products are also available with silver for its anti-microbial effects [15-17]. However, while these dressings and topical therapies are effective, chronic wounds cannot be cured without proper debridement, offloading, and management of infection [18]. Advanced therapies like negative pressure wound therapy and hyperbaric oxygen therapy have proven effective, but they require repeated hospital appointments, thus reduc- ing patient compliance. Other advanced therapies include stem cell (autogenous and allogeneic), amniotic tissue, and umbilical cord-based therapies, for which prospective data have yet to show their efficacy in facilitating wound healing and are quite expensive for the patients [19,20]. With the rise in hard-to-heal chronic and complex acute wounds, de- veloping new strategies that facilitate effective treatment is essential. One of the recent novel strategies coming up on the market is the use of the acellular dermal matrix (ADM). ADM is a type of surgical mesh developed from animal or human skin in which the cells are separated from the support structure [21]. ADM stimulates angiogenesis and provides a scaffold for the formation of granulation tissue. Formerly regarded as merely passive collagen structures that offer a framework for cellular growth, ADMs are now recognized for their active role in tissue regeneration while interacting with growth factors involved in the wound healing process [22,23]. Among the many clinically available acellular der- mal matrices, the acellular fish skin graft (AFSGs) product Kerecis (Coloplast; Humlebaek, Denmark) is gaining pop- ularity among hard-to-heal wounds [24]. It is an omega-3 fatty acid-rich fish skin product derived from north Atlan- tic cod (Gadus morhua) found in Ísafjörður, Iceland. It is homologous to any human skin, and it retains its natural omega-3 polyunsaturated fatty acids [25]. In addition, there is no documented risk of viral disease transmission from cold-water fish to humans [26]. The key efficacy of AFSGs lies in their lipid profile. They are abundant in omega-3 poly- unsaturated fatty acids, particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), known for their anti-inflammatory and antimicrobial characteristics [27,28]. Thus, AFSGs obtained from Atlantic cod offer an interest- ing option for treating complicated wounds. By complicated wounds, we mean wounds that show delayed healing due to factors such as poor vascularization, chronic inflammation, infection, and high recurrence rates, commonly observed in diabetic foot ulcers, venous ulcers, and full-thickness biopsy wounds. Although acute biopsy wounds may generally heal faster than chronic ulcers, full-thickness biopsy wounds can still present complications. Due to complexities in their healing mechanisms, these wounds often require advanced wound care approaches beyond standard-of-care treatments. This systematic review grouped all the existing study cohorts together to investigate the efficacy of fish skin grafting in healing complicated wounds. Objectives This systematic review aimed to summarize the efficacy of AFSGs on complicated wounds using evidence from ex- isting published studies. It was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 2020 guidelines (Figure 1 and Table S1). The review is registered in the International Pro- spective Register of Systematic Reviews (PROSPERO) under the registration ID - 382204. Review | Dermatol Pract Concept. 2025;15(2):4945 3 Methods Data Sources We performed a systematic search of the medical literature using the electronic databases ScienceDirect, PubMed, Co- chrane, and Google Scholar. The search for unpublished studies was done on Clinicaltrials.gov. The following terms were variously combined in the search strategy: “acellular fish skin”, “fish skin grafts”, “fish skin”, “wound healing”, “diabetic foot ulcer”, “venous foot ulcer”, “acute biopsy wounds”. In addition to this, the reference lists of the in- cluded reports were screened manually in order to get rele- vant publications. Selection Criteria Selection of the relevant articles was performed by employing the Rayyan online tool; both title-specific and abstract- specific searches were carried out using the tool. The independently nominated articles were matched, and a consensus was reached after multiple discussions among the authors. The selected reports were then subjected to full-text investigations per the inclusion and exclusion criteria. Complicated wounds were defined as “hard-to-heal” wounds that show delayed healing due to factors like chronic inflammation, limited vas- cularity, infection, deep cuts involving subcutaneous tissue, and high recurrence rates [29]. Original articles in English reporting the efficacy of fish skin grafts for wound healing were considered as the essential inclusion criterion. Exclusion criteria included a) review articles, b) case series with fewer than five enrolled patients, and c) book chapters. Data Extraction The studies eligible according to the inclusion criteria were assessed for outcome measures like total re-epithelialization time, additional interventions, adverse events, and follow-up for a dressing change. The data were extracted from the full- text articles onto an Excel spreadsheet. All the discrepancies were rectified by the authors, and the data were approved by the principal investigator. Quality Assessment The selected publications were assessed for quality by employ- ing the RoB 2 tool for randomized studies and the ROBINS-I tool for non-randomized studies/case series (Figure 2). The RoB 2 tool for randomized trials (RCTs) covers six domains for bias assessment ranging from the randomization pro- cess to the selection of reported result. ROBINS-I tool for non-randomized trials, on the other hand, includes seven domains to assess the quality of the studies. The authors in- dependently evaluated the data before reaching a consensus on risk-of-bias judgments (Tables S2 and S3). Results A total of nine studies reporting the efficacy of AFSGs in patients with complicated wounds, including DFUs, venous Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 2020 - flow diagram of the inclusion and exclusion criteria. *Pubmed, ScienceDirect, Google Scholar, Cochrane. 4 Review | Dermatol Pract Concept. 2025;15(2):4945 area of wound in the collagen alginate group, while the fish skin group exhibited a reduction of 72.8%. Similar results were reported by Zehnder et al.[32] (25), who reported that chronic DFUs were completely healed in 12.42 weeks. Dorweiler et al. [33] also included chronic DFU patients who were additionally administered with antibiotic therapy, analgesics, and opioids. They reported a re-epithelialization time of about 23 weeks, with a significant reduction in an- algesics. The difference in mean re-epithelialization time be- tween the studies by Lullove et al. and Dorweiler et al. can be attributed to the wound types. Lullove et al. studied mild ulcers (Texas grade 1A/1C), while Dorweiler et al. included patients with more severe lower limb ulcers involving ampu- tation and exposed bone, which are harder to heal. Notably, Dorweiler et al. mentioned that adequate debridement, bac- terial control, and tissue perfusion are the prerequisites for fish skin application to the wounded site to attain minimum re-epithelialization time. In the case of biopsy wounds, the total healing time was reported in the range of 3.5 to 4 weeks, with a mean and me- dian value of 3.75 weeks. In contrast, without any treatment, it took six weeks to achieve just 50% of the wound’s tensile strength [34]. Kirsner et al. concluded that in comparison to biopsy wounds treated with dehydrated human amnion- chorion membrane (dHACM), wounds treated with fish skin showed a notably faster healing rate (hazard ratio F2.37; 95% CI: 1.75–3.22; P=0.0014). The study also reported that wounds treated with dHACM were, on average, 76% more expensive to treat than those treated with acellular fish foot ulcers, acute biopsy wounds, et cetera, were included in this systematic review. All the included studies were in English. The primary outcome assessed was the re- epithelialization time by the application of AFSGs. Tables 1 and 2 summarize the baseline characteristics and study out- comes of the studies included in the systematic review. Total Re-epithelialization Time The primary focus of all the studies included in this sys- tematic review was the total re-epithelialization time of the treated wounds. Based on the studies analyzed that reported the healing duration of DFUs, the total re-epithelialization time ranged from seven to 23 weeks, with a mean duration of 15 ± 8 weeks and a median value of 12.42 weeks. This is in contrast with the median healing time of six months in 1999/2000 and 6.6 months in 2011/2012 with standard of care (SoC) procedures [30]. A recent study reported that 50.9% of diabetic feet do not heal by the end of 12 weeks, with 1.3% of deaths [31]. Thus, AFSG shows significant im- provement over SoC treatment. Woodrow et al. conducted a prospective study on nine patients with DFU in the United Kingdom and reported a mean re-epithelialization time of 20.42 weeks. Lullove et al. conducted two RCTs in consecu- tive years with 94 and 49 chronic DFU patients (Texas grade 1A/1C), reporting a mean of seven and 12 weeks, respec- tively. Both the studies compared AFSG with collagen algi- nate dressings and noted a statistically significant difference in patient outcomes. The team reported that by the end of six weeks, there was a 41.2% reduction in the percentage Figure 2. Risk of bias judgement of the included non-randomized and randomized studies using Cochrane’s ROBINS-I and RoB 2 tools, respectively. Review | Dermatol Pract Concept. 2025;15(2):4945 5 T ab le 1 . B as el in e C ha ra ct er is ti cs o f Pa ti en ts in R ep or ts E va lu at in g th e A pp lic at io n of A ce llu la r Fi sh S ki n G ra ft s fo r W ou nd H ea lin g. St ud y N o A ut ho r St ud y D es ig n W ou nd T yp e Pa ti en ts A na ly ze d (C /T ) A ge ( Y ea rs ) R ac e/ C ou nt ri es W ou nd S iz e W ou nd C la ss ifi ca ti on C om pa ra to r 1 W oo dr ow et a l. 20 19 Pr os pe ct iv e ob se rv at io na l st ud y D ia be ti c fo ot u lc er 9 65 ( 54 - 8 8) U ni te d K in gd om 0. 94 c m ² to 29 .5 5c m ² A cu te ( 6) ; ch ro ni c (3 ) Te xa s gr ad e 1 to 3 ² N on e 2 L ul lo ve et a l. 20 22 Pr os pe ct iv e R C T D ia be ti c fo ot u lc er 94 ( 48 /4 6) 58 (4 8. 5- 64 ) U SA 1 cm ² to 2 5 cm ² C hr on ic ; T ex as gr ad e 1A /1 C C ol la ge n al gi na te dr es si ng ( fib ra co l pl us c ol la ge n w ou nd dr es si ng w it h al gi na te ; 3 M ) 3 L ul lo ve et a l. 20 21 Pr os pe ct iv e R C T D ia be ti c fo ot u lc er 49 ( 24 /2 5) 64 .9 5 U SA 1 cm ² to 2 5 cm ² C hr on ic ; T ex as gr ad e 1A /1 C C ol la ge n al gi na te dr es si ng 4 Z eh nd er et a l. 20 22 O ut co m e- ba se d m od el s tu dy V en ou s le g ul ce rs a nd di ab et ic f oo t ul ce rs 42 ( 21 /2 1) N R * Sw it ze rl an d 1. 4 cm ² (0 .1 2 cm ² to 36 .2 c m ²) C hr on ic 4 w ee ks o f St an da rd - of -c ar e (S O C *) th er ap y 5 D or w ei le r et a l. 20 18 Pr os pe ct iv e ob se rv at io na l st ud y D ia be ti c fo ot u lc er (A m pu ta ti on p at ie nt s in cl ud ed ) 8 50 - 1 01 G er m an y 23 ± 1 8 cm ² (r an ge 6 –6 3c m ²) C hr on ic N on e 6 K ir sn er et a l. 20 20 D ou bl e- bl in d pr os pe ct iv e R C T Fu ll- th ic kn es s bi op sy w ou nd s 85 24 .1 (1 9- 51 ) Ic el an d (8 4 C au ca si an s an d 1 of A fr ic an or ig in ) 0. 12 c m ² A cu te dH A C M ( de hy dr at ed hu m an A M N IO N /c ho ri on m em br an e) 7 B al du rs so n et a l. 20 15 D ou bl e- bl in d pr os pe ct iv e R C T W ho le t hi ck ne ss b io ps y w ou nd s 81 ( 40 /4 1) N R A fr ic an , H is pa ni c, C au ca si an 0. 12 c m ² A cu te Po rc in e Sm al l- In te st in e Su bm uc os a 8 G ui do C ip ra nd i et a l. 20 24 C as e se ri es A ni m al b it e, s ac ra l p re ss ur e ul ce r, m ac hi ne ry a cc id en t, su rg ic al d eh is ce nc e 15 8 ye ar s 9 m on th s It al y 5. 8 cm ² C hr on ic N on e 9 Ib ra hi m C he rr y et a l. 20 23 C as e se ri es 3rd d eg re e bu rn , c hr on ic w ou nd o n sc al p, s ca r re vi si on , h id ra de ni ti s su pp ur at iv e 5 1, 2, 9 ,1 4, 16 Sw it ze rl an d 53 c m 2 C hr on ic , sc ar ri ng N on e A bb re vi at io ns : C /T = C on tr ol /T re at m en t; R C T = r an do m iz ed c on tr ol le d tr ia l; SO C = s ta nd ar d of c ar e (o ff lo ad in g, a pp ro pr ia te d eb ri de m en t, an d m oi st w ou nd c ar e) . 6 Review | Dermatol Pract Concept. 2025;15(2):4945 T ab le 2 . C lin ic al S tu di es R ep or ti ng t he A pp lic at io n of A ce llu la r Fi sh S ki n G ra ft f or C om pl ic at ed W ou nd s. St ud y N o. A ut ho r D re ss in g Pr oc ed ur e an d T im e Pe ri od A dd it io na l In te rv en ti on A dv er se E ve nt s W ou nd O bs er va ti on T ec hn iq ue T ot al R e- ep it he lia liz at io n T im e C on cl us io n 1 W oo dr ow et a l. 20 19 D re ss in gs w er e ch an ge d w ee kl y fo r 6 w ee ks N on e N o sk in ir ri ta ti on , n o in cr ea se d pa in . A m pu ta ti on - 1 D ig it al p ho to gr ap hy an d Im ag eJ s of tw ar e 20 .4 2 w ee ks Fi sh s ki n gr af ts a cc el er at e w ou nd he al in g. 2 L ul lo ve et  a l. 20 22 D re ss in gs w er e ch an ge d w ee kl y fo r 6 w ee ks a nd 1 2 w ee ks , re sp ec ti ve ly N on e N R Si te in ve st ig at or ’s as se ss m en t. R ev ie w ed b y a va sc ul ar s ur ge on , a po di at ri st , a nd a n in te rn al m ed ic in e sp ec ia lis t. 7 w ee ks St at is ti ca lly s ig ni fic an t di ff er en ce in he al in g w as o bs er ve d be tw ee n pa ti en ts tr ea te d w it h A FS G s an d th os e tr ea te d w it h co lla ge n al gi na te d re ss in gs . 3 L ul lo ve et  a l. 20 21 D re ss in gs w er e ch an ge d w ee kl y fo r 1 2 w ee ks N on e. D eb ri de m en t w as d on e be fo re in it ia ti on . N R Si te in ve st ig at or ’s as se ss m en t 12 w ee ks Fi sh s ki n gr af ti ng c an b e em pl oy ed fo r pa ti en ts w it h ch ro ni c D FU in co m bi na ti on w it h SO C t he ra py . 4 Z eh nd er et  a l. 20 22 D re ss in gs w er e ch an ge d w ee kl y. 8 w ee ks N on e N R D ig it al P ho to gr ap hy 12 .4 2 w ee ks Fi sh s ki n gr af ts s ho w f as te r he al in g ra te s th an S O C t he ra py . 5 D or w ei le r et a l. 20 18 D re ss in gs w er e ch an ge d w ee kl y un ti l c om pl et e w ou nd h ea lin g A nt ib io ti c th er ap y, an al ge si cs a nd op io id s N o in fe ct io ns o r im m un e re ac ti on s oc cu rr ed d ur in g th e tr ea tm en t pe ri od . Si gn ifi ca nt p ai n re du ct io n. D ig it al P ho to gr ap hy 23 ± 1 0 w ee ks R ed uc ti on in a na lg es ic s up ta ke . F is h sk in g ra ft is e ff ec ti ve in t re at in g co m pl ic at ed w ou nd s 6 K ir sn er et  a l. 20 20 D re ss in gs w er e ch an ge d w ee kl y fo r 6 w ee ks N on e R as he s- 6 E ry th em a - 6 Pa in - 7 Sk in ir ri ta ti on w it h di sc ha rg e - 2 H yp er gr an ul at io n - 2 D ig it al P ho to gr ap hy 3. 5 w ee ks Fi sh s ki n gr af t tr ea te d w ou nd s he al ed si gn ifi ca nt ly f as te r (h az ar d ra ti o 2. 37 ) w he n co m pa re d to d H A C M -t re at ed w ou nd s. Review | Dermatol Pract Concept. 2025;15(2):4945 7 7 B al du rs so n et a l. 20 15 O n ea ch r et ur n vi si t, if t he tr ea tm en t m at er ia l w as co m pl et el y in ta ct , i t w as le ft in t he w ou nd . I f no t, ne w m at er ia l w as a pp lie d to t he w ou nd ; 4 w ee ks N on e E ry th em a - 1 Sk in ir ri ta ti on a nd di sc ha rg e - 2 N o in fe ct io n w as r ep or te d. N o im m un e re ac ti on s re co rd ed . D ig it al p ho to gr ap hy 4 w ee ks Fi sh s ki n gr af t he al ed t he w ou nd s si gn ifi ca nt ly f as te r th an P or ci ne S m al l- In te st in e Su bm uc os a 8 G ui do C ip ra nd i et  a l. 20 24 A s pe r re qu ir em en t (2 -3 d re ss c ha ng es w er e re qu ir ed ); 5 4 w ee ks N eg at iv e pr es su re w ou nd th er ap y to 1 2/ 15 pa ti en ts N on e D ig it al p ho to gr ap hy 12 .4 d ay s N o re si du al s ca rr in g w as o bs er ve d af te r 12 m on th s. T he o pe ra ti ng t im e w as r ed uc ed t o <6 0 m in . A cc el er at ed w ou nd h ea lin g w it h fu ll gr an ul at io n ti ss ue c ov er ag e w as o bs er ve d in 1 00 % of t he p at ie nt s. 9 Ib ra hi m C he rr y et  a l. 20 23 N R Ph ys io th er ap y fo r sc ar m as sa ge N o hy pe rs en si ti vi ty o r al le rg ic r ea ct io n w as re po rt ed . D ig it al p ho to gr ap hy 48 .6 d ay s Fi sh s ki n gr af t pr es en ts s ki n el as ti ci ty , ha s an al ge si c po te nt ia l d ue t o O m eg a- 3 fa tt y ac id s, a nd s ti m ul at e m yo fib ro bl as t ac ti vi ty . Fi sh s ki n ca n be a pp lie d to d iv er se w ou nd t yp es a nd a na to m ic al s it es . A bb re vi at io ns : A FS G = a ce llu la r fi sh s ki n gr af t; N R = n ot r ep or te d; S O C = s ta nd ar d of c ar e of fl oa di ng , a pp ro pr ia te d eb ri de m en t, an d m oi st w ou nd c ar e) . 8 Review | Dermatol Pract Concept. 2025;15(2):4945 factor-beta 1 (TGF-β1), and CD31, all of which are actively involved in the wound healing process [44]. Another study on a rat wound model found that AFSGs stimulate factors crucial to repairing skin, blood vessels, and nerves, including fibroblast growth factor (FGF) and epidermal growth factor (EGF), while preventing external infections [45]. As a part of the clinical evidence, a case study on a pa- tient suffering from hemophilia and chronically infected ulcerations on a dehisced transmetatarsal amputated left foot showed that by using six applications of AFSGs, the ulcerations healed in 14 weeks [46]. Another case study on split-thickness donor sites showed that on the application of fish skin graft, the wounds healed on average in 11.5 days, with zero incidence of any kind of adverse event [47]. A re- cent case study in the USA applied AFSG to a 61-year-old immunodeficient patient with a complex right flank wound, stool contamination, necrotizing soft tissue infection from perforated colon cancer, and sepsis. AFSG healed the wound by exhibiting angiogenic and anti-inflammatory activity [48]. Another recent case study on two patients aged 62 and 42 years with chronic intra-abdominal catastrophe post- damage control laparotomy reported that the use of AFSG sped up the skin graft placement for both patients, reduced the need for wound vacuum-assisted closure (VAC), and con- sequently shortened their hospital stay [49]. The present study demonstrates that AFSGs show both regenerative and antimicrobial effects for healing compli- cated wounds. AFSGs consist of proteoglycans, glycosami- noglycans, fibrin, and collagen, which act as a substitute for human skin [50]. AFSGs regulate matrix metallopro- teinase (MMP) activity by providing a breakdown site for the scaffold instead of the host tissue and extracellular ma- trix (ECM) components. This regulation prevents excessive pro-inflammatory cytokines, aiding wound healing and maintaining cellular processes [51]. AFSGs have higher levels of omega-3 fatty acids (DHA and EPA) than do mammalian grafts, making up 10.7% and 8.5%, respectively, of the lipid content. Omega-3 fatty acids accelerate wound healing, as shown in a study where healthy patients taking EPA (1.6 g) and DHA (1.2 g) healed blisters faster by day 5 compared to a control group on mineral oil and low-dose aspirin [52]. Additionally, AFSGs are also known to show anti-microbial effects, as depicted by Baldursson et al. [38] A recent study using a two-chamber assay on Staphylococcus aureus cul- tures found that fish skin acted as a bacterial barrier. The barrier function of fish skin improved by 80% when spiked with over 10% omega-3 fatty acids [53]. Also, researchers have stated that colony-forming units found in fish skin con- sist of non-infectious microbiota [54]. AFSGs have taken over mammalian skin grafts as fish skin does not transmit any disease, like variant Creutzfeldt-Jakob disease or bovine spongiform encephalopathy [55]. Therefore, there is no need skin. Baldursson et al. employed the noninferiority test to assess the effectiveness of fish skin ADM in comparison to porcine small-intestine submucosa extracellular matrix for the healing of 162 full-thickness biopsy wounds (4 mm) on the forearms of 81 volunteers. They reported that AFSG was noninferior and healed at an average of 28 days. Dressing Changes Different teams of researchers adopted different procedures for dressing the fish skin graft as it mainly depended upon the type of wound being treated. All the studies reporting the application of AFSGs on DFUs adopted a weekly change of dressings [32], [33], [35], [36]. The same procedure was adopted by Kirsner et al. for acute biopsy wounds. On av- erage, each subject received approximately 1.6 applications of the AFSG, whereas the dHACM group received approx- imately 1.4 applications per wound, showing no significant difference between the two groups [37]. Studies on acute biopsy wounds by Baldursson et al. also employed AFSGs but changed the dressing only if the fish skin graft was not completely intact [38], [39]. Adverse Events Woodrow et al. reported no case of skin irritation and in- creased pain when treating DFUs with AFSG, but the team also reported a single case of amputation in spite of the pa- tient’s undergoing treatment with AFSGs [35]. No adverse event was reported by Lullove et al. and by Zehnder et al in DFU and venous foot ulcer patients undergoing fish skin grafting [32], [36]. On similar grounds, Dorweiler et al. stated that no immune reactions or infections were ob- served when employing AFSG during the whole treatment period for DFUs. Moreover, the matrix provided antinoci- ceptive and anti-inflammatory effects [33]. For acute biopsy wounds, Kirsner et al. reported the development of rashes, erythema, pain, hyper granulation, and skin irritation with discharge on the application of AFSG [37]. Similarly, ery- thema and skin irritation with discharge was reported by Baldursson et al. when fish skin graft was used for biopsy wounds. Additionally, the team recorded no infection or im- mune reaction [38]. Conclusions There exists evidence demonstrating the potential applica- tion of acellular dermal matrix of marine origin for wound healing in human subjects [40] as well as in pre-clinical mod- els [41-43]. A recent study on rat and mini-pig skin wound models reported that AFSGs significantly accelerated wound healing through granulation growth, angiogenesis, and col- lagen deposition. The team also noted a high expression of alpha-smooth muscle actin (α-SMA), transforming growth Review | Dermatol Pract Concept. 2025;15(2):4945 9 employed for their regenerative effects but also for their an- tiseptic properties. However, as AFSGs are a relatively new strategy, large-cohort studies are needed to assess their po- tential for wound healing. In addition, upcoming research should focus on novel strategies like network pharmacology [58], [59], nano-hydrogel based dressings [60], stem cell technology [61], and so on to develop new molecules and approaches to achieve accelerated wound healing. References 1. R. Thakur, N. Jain, R. Pathak, and S. S. Sandhu, “Practices in wound healing studies of plants,” Evid Based Complement Alter- nat Med, vol. 2011, 2011, DOI: 10.1155/2011/438056. 2. C. K. Sen, “Human Wound and Its Burden: Updated 2020 Compendium of Estimates,” https://home.liebertpub.com/wound, vol. 10, no. 5, pp. 281–292, Mar. 2021, DOI: 10.1089/WOUND .2021.0026. 3. M. Baba, W. A. Davis, P. E. Norman, and T. M. E. Davis, “Temporal changes in the prevalence and associates of foot ulceration in type 2 diabetes: The Fremantle Diabetes Study,” J Diabetes Complications, vol. 29, no. 3, pp. 356–361, Apr. 2015, DOI: 10.1016/J.JDIACOMP.2015.01.008. 4. D. G. ARMSTRONG, null D.P.M., and L. A. LAVERY, “Diabetic Foot Ulcers: Prevention, Diagnosis and Classification,” Am Fam Physician, vol. 57, no. 6, pp. 1325–1332, Mar. 1998, Accessed: Nov. 17, 2022. [Online]. Available: https://www.aafp.org/pubs /afp/issues/1998/0315/p1325.html 5. M. Á. Tresierra-Ayala and A. García Rojas, “Association between peripheral arterial disease and diabetic foot ulcers in patients with diabetes mellitus type 2,” Medicina Universitaria, vol. 19, no. 76, pp. 123–126, Jul. 2017, DOI: 10.1016/J.RMU.2017.07.002. 6. M. Asaf, N. Salim, M. Tuffaha, and N. A. Salim, “Challenging the Use of Bandage Compression as the Baseline for Evaluating the Healing Outcomes of Venous Leg Ulcer-Related Compression Therapies in the Community and Outpatient Setting: An Integra- tive Review,” Dubai Medical Journal, vol. 1, no. 1–4, pp. 19–25, Nov. 2018, DOI: 10.1159/000494217. 7. J. Spiliotis et al., “Wound dehiscence: is still a problem in the 21th century: a retrospective study,” World Journal of Emergency Surgery, vol. 4, no. 1, p. 12, 2009, DOI: 10.1186/1749-7922-4-12. 8. V. K. Shukla, M. A. Ansari, and S. K. Gupta, “Wound healing research: A perspective from India,” International Journal of Lower Extremity Wounds, vol. 4, no. 1, pp. 7–8, Mar. 2005, DOI: 10.1177/1534734604273660. 9. A. P. Veith, K. Henderson, A. Spencer, A. D. Sligar, and A. B. Baker, “Therapeutic strategies for enhancing angiogenesis in wound healing,” Adv Drug Deliv Rev, vol. 146, pp. 97–125, Jun. 2019, DOI: 10.1016/j.addr.2018.09.010. 10. Y. Niu, Q. Li, Y. Ding, L. Dong, and C. Wang, “Engineered de- livery strategies for enhanced control of growth factor activities in wound healing,” Adv Drug Deliv Rev, vol. 146, pp. 190–208, Jun. 2019, DOI: 10.1016/j.addr.2018.06.002. 11. E. M. Tottoli, R. Dorati, I. Genta, E. Chiesa, S. Pisani, and B. Conti, “Skin Wound Healing Process and New Emerging Tech- nologies for Skin Wound Care and Regeneration,” Pharmaceutics, vol. 12, no. 8, p. 735, Aug. 2020, DOI: 10.3390/pharmaceutics 12080735. for a robust sterilization process for AFSGs [56]. Addition- ally, Baldursson et al. reported that fish skin-derived ADM treats full-thickness wounds without changing autoantibod- ies, indicating no autoimmune response in humans. [38]. AFSG rich in omega-3 fatty acid is easily available worldwide as a vacuum-dried product. The processing of the product is gentle, which enables it to retain its molecular com- position and omega-3 polyunsaturated fatty acids (PUFA). Moreover, keeping sustainability in mind, Atlantic cod are not farmed and are always line-caught, which is highly reg- ulated by the government of Iceland. Present indications, as stated by the company’s official website, include partial and full-thickness wounds, trauma wounds, burns, soft tissue reinforcement, surgical wounds, DFUs, venous ulcers, pres- sure ulcers, and draining wounds [49]. However, in spite of including full-thickness wounds as a part of the applicabil- ity of AFSGs, mild adverse events such as rashes, erythema, hyper granulation and skin irritation with discharge were observed by Kirsner et al. and by Baldursson et al. [37-38]. Thus, extra precautions should be taken when treating acute biopsy wounds with AFSGs. The present study highlights the potential of AFSGs as a regenerative and antimicrobial solution for complex wound healing. It should also be noted that adequate debridement and SoC should not be overlooked when employing AFSGs for good patient outcomes. All the studies included in this systematic review, in conjunction with a recent cost analysis published by Winters et al.[57] based on a Monte Carlo sim- ulation [57] reporting that fish skin grafting is 93.6% more likely to be a cost-effective choice, demonstrate the value and suitability of the procedure in the years to come. The relevance of existing reports on the efficacy of AFSGs for wound healing is limited, as this therapeutic strategy is relatively new. As a result, there are fewer studies available on the applicability of fish skin in wound healing. Trials should be designed by widening the scope of wounds included in the studies, e.g., venous foot ulcers and many such chronic con- ditions. Moreover, a meta-analysis could not be conducted due to the heterogeneity of study designs and outcome mea- sures across the included studies. Additionally, the lack of a homogeneous control group across studies limited the ability to directly compare the outcomes. Thus, future studies with standardized methodologies and control groups are needed to validate the effectiveness of AFSG for complicated wound management.The available literature suggests that AFSGs are effective for treating complex wounds. AFSGs are able to heal the whole wound area at a faster rate, demonstrate anti-inflammatory and antinociceptive effects, cause less pain, and decrease the number of follow-ups for of dressing changes. One of the major findings of this systematic review is that antibiotics need not be administered in association with fish skin grafting. Therefore, AFSGs can not only be 10 Review | Dermatol Pract Concept. 2025;15(2):4945 26. S. Rakers et al., “‘Fish matters’: the relevance of fish skin biol- ogy to investigative dermatology,” Exp Dermatol, vol. 19, no. 4, pp. 313–324, Apr. 2010, DOI: 10.1111/j.1600-0625.2009.01059.x. 27. M. Sun, J. Dong, Y. Xia, and R. Shu, “Antibacterial activities of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) against planktonic and biofilm growing Streptococcus mutans,” Microb Pathog, vol. 107, pp. 212–218, Jun. 2017, DOI: 10.1016/j.micpath.2017.03.040. 28. M. Sun, Z. Zhou, J. Dong, J. Zhang, Y. Xia, and R. Shu, “Antibac- terial and antibiofilm activities of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) against periodontopathic bac- teria,” Microb Pathog, vol. 99, pp. 196–203, Oct. 2016, DOI: 10.1016/j.micpath.2016.08.025. 29. F. Bassetto, C. Scarpa, and F. Facchin, “Complicated Wounds,” in Textbook of Plastic and Reconstructive Surgery, Cham: Springer International Publishing, 2022, pp. 27–38. DOI: 10.1007/978-3-030-82335-1_3. 30. M. L. B. Sørensen, R. B. Jansen, T. Wilbek Fabricius, B. Jørgensen, and O. L. Svendsen, “Healing of Diabetic Foot Ulcers in Patients Treated at the Copenhagen Wound Healing Center in 1999/2000 and in 2011/2012,” J Diabetes Res, vol. 2019, pp. 1–9, Sep. 2019, DOI: 10.1155/2019/6429575. 31. A. C. Yelland et al., “Impact of case-mix adjustment on observed variation in the healing of diabetic foot ulcers at 12-weeks using data from the National Diabetes Foot Care Audit of England and Wales: A cohort study,” Diabetic Medicine, vol. 40, no. 1, Jan. 2023, DOI: 10.1111/dme.14959. 32. T. Zehnder and M. Blatti, “Faster Than Projected Healing in Chronic Venous and Diabetic Foot Ulcers When Treated with Intact Fish Skin Grafts Compared to Expected Healing Times for Standard of Care: An Outcome-Based Model from a Swiss Hos- pital,” International Journal of Lower Extremity Wounds, 2022, DOI: 10.1177/15347346221096205. 33. B. Dorweiler et al., “The marine Omega3 wound matrix for treat- ment of complicated wounds: A multicenter experience report,” Gefasschirurgie, vol. 23, pp. 46–55, Aug. 2018, DOI: 10.1007 /S00772-018-0428-2. 34. A. E. Rivera and J. M. Spencer, “Clinical aspects of full-thickness wound healing,” Clin Dermatol, vol. 25, no. 1, pp. 39–48, Jan. 2007, DOI: 10.1016/j.clindermatol.2006.10.001. 35. T. Woodrow, T. Chant, and H. Chant, “Treatment of diabetic foot wounds with acellular fish skin graft rich in omega-3: a prospec- tive evaluation,” https://DOI.org/10.12968/jowc.2019.28.2.76, vol. 28, no. 2, pp. 76–80, Feb. 2019, DOI: 10.12968/JOWC .2019.28.2.76. 36. E. Lullove, B. Liden, … P. M.-… : a C. of, and undefined 2022, “Evaluating the effect of omega-3-rich fish skin in the treatment of chronic, nonresponsive diabetic foot ulcers: penultimate anal- ysis of a multicenter, prospective,” europepmc.org, Accessed: Nov. 29, 2022. [Online]. Available: https://europepmc.org/ article/med/35797557 37. R. S. Kirsner et al., “Fish skin grafts compared to human amnion/ chorion membrane allografts: A double-blind, prospective, ran- domized clinical trial of acute wound healing,” Wiley Online Library, vol. 28, no. 1, pp. 75–80, Jan. 2019, DOI: 10.1111 /wrr.12761. 38. B. T. Baldursson, H. Kjartansson, F. Konrádsdóttir, P. Gudnason, G. F. Sigurjonsson, and S. H. Lund, “Healing rate and autoim- mune safety of full-thickness wounds treated with fish skin acel- lular dermal matrix versus porcine small-intestine submucosa: 12. S. Jacobsen, “Topical Wound Treatments and Wound-Care Prod- ucts,” in Equine Wound Management, Wiley, 2016, pp. 75–103. DOI: 10.1002/9781118999219.ch5. 13. K. Barrigah-Benissan, J. Ory, A. Sotto, F. Salipante, J.-P. Lavigne, and P. Loubet, “Antiseptic Agents for Chronic Wounds: A Sys- tematic Review,” Antibiotics, vol. 11, no. 3, p. 350, Mar. 2022, DOI: 10.3390/antibiotics11030350. 14. M. Abd Elhakeem, N. Zaher, A. Ezzat, A. Ashraf, and O. Seif, “Methacrylate Powder Dressing in Traumatic, Pressure sore, Venous ulcers and Burn Wounds Healing,” Benha Medical Journal, vol. 0, no. 0, pp. 0–0, Aug. 2022, DOI: 10.21608/bmfj .2022.128226.1560. 15. S. A. Chowdhry, “Use of oxidized regenerated cellulose (ORC)/ collagen/silver-ORC dressings to help manage skin graft donor site wounds,” JPRAS Open, vol. 22, pp. 33–40, Dec. 2019, DOI: 10.1016/j.jpra.2019.08.001. 16. E. B. Jude, J. Apelqvist, M. Spraul, and J. Martini, “Prospective randomized controlled study of Hydrofiber® dressing containing ionic silver or calcium alginate dressings in non-ischaemic dia- betic foot ulcers,” Diabetic Medicine, vol. 24, no. 3, pp. 280–288, Mar. 2007, DOI: 10.1111/j.1464-5491.2007.02079.x. 17. P. Muangman, C. Pundee, S. Opasanon, and S. Muangman, “A prospective, randomized trial of silver containing hydrofiber dressing versus 1% silver sulfadiazine for the treatment of partial thickness burns,” Int Wound J, vol. 7, no. 4, pp. 271–276, Aug. 2010, DOI: 10.1111/j.1742-481X.2010.00690.x. 18. R. G. Frykberg and J. Banks, “Challenges in the Treatment of Chronic Wounds,” Adv Wound Care (New Rochelle), vol. 4, no. 9, pp. 560–582, Sep. 2015, DOI: 10.1089/wound.2015.0635. 19. D.-C. Ding, Y.-H. Chang, W.-C. Shyu, and S.-Z. Lin, “Human Umbilical Cord Mesenchymal Stem Cells: A New Era for Stem Cell Therapy,” Cell Transplant, vol. 24, no. 3, pp. 339–347, Mar. 2015, DOI: 10.3727/096368915X686841. 20. N. Kosaric, H. Kiwanuka, and G. C. Gurtner, “Stem cell thera- pies for wound healing,” Expert Opin Biol Ther, vol. 19, no. 6, pp.  575–585, Jun. 2019, DOI: 10.1080/14712598.2019.1596257. 21. “Acellular Dermal Matrix (ADM) Products Used in Implant-Based Breast Reconstruction Differ in Complication Rates: FDA Safety Communication | FDA.” Accessed: Nov. 18, 2022. [Online]. Available: https://www.fda.gov/medical-devices/safety -communications/acellular-dermal-matrix-adm-products-used -implant-based-breast-reconstruction-differ- complication 22. C. V. Ellis and D. A. Kulber, “Acellular Dermal Matrices in Hand Reconstruction,” Plast Reconstr Surg, vol. 130, pp. 256S-269S, Nov. 2012, DOI: 10.1097/PRS.0b013e318265a5cf. 23. A. Pabst et al., “Biomechanical Characterization of a New Acel- lular Dermal Matrix for Oral Soft Tissue Regeneration,” Journal of Investigative Surgery, vol. 35, no. 6, pp. 1296–1303, Jun. 2022, DOI: 10.1080/08941939.2022.2047245. 24. T. H. Kim, J. H. Park, H. G. Jeong, and S. Y. Wee, “The Utility of Novel Fish-Skin Derived Acellular Dermal Matrix (Kerecis) as a Wound Dressing Material,” Journal of Wound Management and Research, vol. 17, no. 1, pp. 39–47, Feb. 2021, DOI: 10.22467 /JWMR.2020.01228. 25. T. O’Donnell, M. Passman, … W. M.-J. of vascular, and undefined 2014, “Management of venous leg ulcers: clinical practice guidelines of the Society for Vascular Surgery® and the American Venous Fo- rum,” jvascsurg.org, Accessed: Nov. 18, 2022. [Online]. Available: https://www.jvascsurg.org/article/S0741-5214(14)00851 -9/abstract Review | Dermatol Pract Concept. 2025;15(2):4945 11 /paper/15272388/skin-development-in-bony-fish-with-partic- ular-emphasis-on-collagen-deposition-in-the-dermis-of-the-ze- brafish-danio-rerio 51. S. R. Van Doren, “Matrix metalloproteinase interactions with collagen and elastin,” Matrix Biology, vol. 44–46, pp. 224–231, May 2015, DOI: 10.1016/j.matbio.2015.01.005. 52. J. C. McDaniel, K. Massey, and A. Nicolaou, “Fish oil supple- mentation alters levels of lipid mediators of inflammation in mi- croenvironment of acute human wounds,” Wound Repair and Regeneration, vol. 19, no. 2, pp. 189–200, Mar. 2011, DOI: 10.1111 /j.1524-475X.2010.00659.x. 53. S. Magnusson, B. Baldursson, … H. K.-M., and undefined 2017, “Regenerative and antibacterial properties of acellular fish skin grafts and human amnion/chorion membrane: implications for tissue preservation in combat casualty,” academic.oup.com, Ac- cessed: Dec. 01, 2022. [Online]. Available: https://academic.oup. com/milmed/article-abstract/182/suppl_1/383/4209412 54. E. Lima-Junior, N. Picollo, and M. Miranda, “Uso da pele de tilápia (Oreochromis niloticus), como curativo biológico oclu- sivo, no tratamento de queimaduras,” Rev Bras Queimadu- ras, vol. 16, no. 1, pp. 10–17, 2017, Accessed: Dec. 01, 2022. [Online]. Available: https://repositorio.ufc.br/handle/riufc/28917 55. P. Brown, R. G. Will, R. Bradley, D. M. Asher, and L. Detwiler, “Bo- vine spongiform encephalopathy and variant Creutzfeldt-Jakob disease: background, evolution, and current concerns.,” Emerg Infect Dis, vol. 7, no. 1, p. 6, 2001, DOI: 10.3201/EID0701 .010102. 56. H. Kjartansson, I. Olafsson, … S. K.-O. J. of M., and undefined 2015, “Use of acellular fish skin for dura repair in an ovine model: a pilot study,” scirp.org, Accessed: Dec. 01, 2022. [On- line]. Available: https://www.scirp.org/html/4-2080131_60730. htm 57. C. Winters, R. S. Kirsner, D. J. Margolis, and J. C. Lantis, “Cost Effectiveness of Fish Skin Grafts Versus Standard of Care on Wound Healing of Chronic Diabetic Foot Ulcers: A Retrospec- tive Comparative Cohort Study.,” Wounds, vol. 32, no. 10, pp. 283–290, Oct. 2020. 58. S. Karhana, S. Dabral, A. Garg, A. Bano, N. Agarwal, and Mohd. A. Khan, “Network pharmacology and molecular docking analysis on potential molecular targets and mechanism of action of BRAF inhibitors for application in wound healing,” J Cell Bio- chem, vol. 124, no. 7, pp. 1023–1039, Jul. 2023, DOI: 10.1002 /jcb.30430. 59. A. Garg et al., “Network pharmacology and molecular docking study-based approach to explore mechanism of benzimidazole- based anthelmintics for the treatment of lung cancer,” J Bio- mol Struct Dyn, pp. 1–22, Sep. 2023, DOI: 10.1080/07391102 .2023.2258419. 60. X. Zhang et al., “Current Progress and Outlook of Nano-Based Hydrogel Dressings for Wound Healing,” Pharmaceutics, vol. 15, no. 1, p. 68, Dec. 2022, DOI: 10.3390/pharmaceutics15010068. 61. N. Kosaric, H. Kiwanuka, and G. C. Gurtner, “Stem cell thera- pies for wound healing,” Expert Opin Biol Ther, vol. 19, no. 6, pp. 575–585, Jun. 2019, DOI: 10.1080/14712598.2019.1596257. A noninferiority study,” International Journal of Lower Extrem- ity Wounds, vol. 14, no. 1, pp. 37–43, Mar. 2015, DOI: 10.1177 /1534734615573661. 39. J. Yoon et al., “Wound healing ability of acellular fish skin and bovine collagen grafts for split-thickness donor sites in burn pa- tients: Characterization of acellular grafts and clinical,” Elsevier, Accessed: Nov. 29, 2022. [Online]. Available: https://www.science direct.com/science/article/pii/S0141813022002914 40. H. Luze, S. P. Nischwitz, C. Smolle, R. Zrim, and L.-P. Kamolz, “The Use of Acellular Fish Skin Grafts in Burn Wound Management—A Systematic Review,” Medicina (B Aires), vol. 58, no. 7, p. 912, Jul. 2022, DOI: 10.3390/medicina58070912. 41. S. Magnusson et al., “Acellular Fish Skin Grafts and Pig Uri- nary Bladder Matrix Assessed in the Collagen-Induced Arthri- tis Mouse Model,” Int J Low Extrem Wounds, vol. 17, no. 4, pp. 275–281, Dec. 2018, DOI: 10.1177/1534734618802899. 42. E. S. Mauer, E. A. Maxwell, C. J. Cocca, J. Ganjei, and D. Spector, “Acellular fish skin grafts for the management of wounds in dogs and cats: 17 cases (2019–2021),” Am J Vet Res, vol. 83, no. 2, pp. 188–192, Feb. 2022, DOI: 10.2460/ajvr.21.09.0140. 43. A. de Souza et al., “Fish collagen for skin wound healing: a systematic review in experimental animal studies,” Cell Tissue Res, vol. 388, no. 3, pp. 489–502, Jun. 2022, DOI: 10.1007 /s00441-022-03625-w. 44. D. Li et al., “Evaluation of a novel tilapia-skin acellular dermis matrix rationally processed for enhanced wound healing,” Mate- rials Science and Engineering: C, vol. 127, p. 112202, Aug. 2021, DOI: 10.1016/j.msec.2021.112202. 45. K. Lv, L. Wang, X. He, W. Li, L. Han, and S. Qin, “Application of Tilapia Skin Acellular Dermal Matrix to Induce Acute Skin Wound Repair in Rats,” Front Bioeng Biotechnol, vol. 9, Feb. 2022, DOI: 10.3389/fbioe.2021.792344. 46. C. Winters, C. is P.-D. F. J, and undefined 2018, “Wound dehis- cence on a diabetic patient with hemophilia and high risk of further amputation successfully healed with omega 3 rich fish skin: a case report,” diabetesonthenet.com, vol. 21, no. 3, 2018, Accessed: Dec. 01, 2022. [Online]. Available: https://diabete sonthenet.com/wp-content/uploads/pdf/dotn5af79c6d5de 192c212a36c077c19189a.pdf 47. K. Alam and S. L. A. Jeffery, “Acellular Fish Skin Grafts for Man- agement of Split Thickness Donor Sites and Partial Thickness Burns: A Case Series,” Mil Med, vol. 184, no. Supplement_1, pp. 16–20, Mar. 2019, DOI: 10.1093/MILMED/USY280. 48. C. Daidone, N. Salim, L. Smith, and A. Raza, “The Role of Fish Skin Xenografts in Healing Complex Wounds: A Brief Case Report,” Cureus, Mar. 2024, DOI: 10.7759/cureus.56156. 49. latifi Rifat and Abbas Smiley, “acellelar fish skin garft use in open abdomen management,” Surgical Technology Internationsl, vol. 42, 2023. 50. D. le Guellec, G. Morvan-Dubois, J. S.-I. J. of, and undefined 2003, “Skin development in bony fish with particular empha- sis on collagen deposition in the dermis of the zebrafish (Danio rerio).,” ijdb.ehu.es, vol. 48, pp. 217–231, 2004, Accessed: Dec. 01, 2022. [Online]. Available: http://www.ijdb.ehu.es/web