87 Synthesis of the Amino Acid-based Polyesteramide for Hydrophilic Modification of Polycaprolactone Xiaoqi Chen *, Lu Bai, Mingguang Hu, Haijun Zhou, Fen Zhang, Yantao Li Institute of Energy Resources, Hebei Academy of Sciences, Shijiazhuang, Hebei Province, 050081, China * Corresponding Author: Xiaoqi Chen Abstract. To solve the problem that the strong hydrophobicity of Polycaprolactone (PCL) was not conducive to cell adhesion and spreading in artificial blood vessels, the amino acid-based polyesteramides (AA-PEAs) material was synthesized using L-phenylalanine, 1,3-propylene glycol and sebacyl chloride for hydrophilic modification of PCL. The chemical structure, water contact angles, and thermal performance, were characterized by 1H NMR, Water contact Angle tester, Thermogravimetric Analyzer, and Differential Scanning Calorimeter. The hydrophilicity of PCL fiber membranes was significantly improved by adding the AA-PEAs. The glass transition temperature (Tg) of the PCL fiber membrane was 34.1℃, which was lower than the human body temperature with the 30% content of AA-PEAs. The melting temperature (Tm) was 55.0℃, which was higher than the human body temperature. It is conducive to maintaining good flexibility under the impact and pressure of blood flow in the body. Keywords: Polycaprolactone (PCL); Amino Acid-based Polyesteramides (AA-PEAs); Hydrophilic Modification; Water Contact Angle. 1. Introduction Polycaprolactone (PCL) is a semi-crystalline biodegradable polyester with a low melting point of 60℃, produced by ring-opening polymerization of ε-caprolactone, and possessing good biocompatibility and permeability [1-2]. The drawbacks of PCL, such as hydrophobic nature and long degradation time, can be overcome by combining it with other polymeric materials; such polymers have been widely used in the field of biomedical engineering[3]. Amino acid-based polyesteramides (AA-PEAs) are another widely used class of polymeric materials. AA-PEAs not only have a chemical structure similar to that of proteins, but can also participate in normal physiological metabolism as pseudo-proteins [4]. After simple hydrolysis or enzymatic degradation, the natural amino acids will be released into the circulation and absorbed [5]. Due to the structural diversity, especially the multiple stereospecific information on different functional groups and amino acids, AA-PEA becomes a promising biomaterial, and some preliminary studies on its structure-property relationships have been conducted [6]. In this paper, the AA-PEAs material was synthesized using L-phenylalanine, 1,3-propanediol and sebacyl chloride as the main raw materials. By blending the AA-PEAs and PCL, the fiber membranes were prepared via electrospinning technology. The influence of AA-PEAs on the hydrophilic properties of electrostatic fiber membranes was emphatically studied, as well as the thermal performance. 2. Experiment 2.1 Materials Polycaprolactone (PCL, Mn=80,000Da), 1,3- Propylene glycol, and Sebacyl chloride were provided by Shanghai Maclean Biochemical Technology Co., L-phenylalanine was supplied by Shanghai Aladdin Biochemical Technology Co., P-methylbenzenesulfonic acid monohydrate was supplied by Alfaesah (China) Chemical Co., Ultra-dry Dichloromethane was supported by Sigma 88 Aldrich (Shanghai) Trading Co., Ethyl Acetate and Anhydrous sodium carbonate were provided by Tianjin Yongda Chemical Reagent Co.. 2.2 Synthesis of amino acid-based polyesteramides (AA-PEAs) The L-phenylalanine, p-toluenesulfonic acid monohydrate and 1,3-propylene glycol were esterified in a molar ratio of 2:2:1 to synthesize phenylalanine propylene diester (Phe). Next, the crude amino acid-based polyesteramides (AA-PEAs) was obtained through interfacial reaction at a molar ratio of 1:1 between phenylalanine propylene diester and sebacyl chloride. After washing with a sufficient amount of deionized water, it was purified through a tetrahydrofuran/ethyl acetate solvent system. Finally, the AA-PEAs were obtained after vacuum drying for later use. Its synthesis path was shown in Figure. 1. Figure 1. The synthetic pathway of polyesteramides. 2.3 Fabrication of PCL/AA-PEAs Electrostatic Fiber Membranes The different ratios of PCL/AA-PEAs were completely dissolved in the mixed solvent of chloroform/dimethyl sulfoxide (CHCl3/DMSO, v/v=4/1), obtaining a spinning solution concentration of 130-150 mg/mL. In this study, the addition amounts of the AA-PEAs were 20%, 30% and 40% respectively. The liquid supply speed was 1.2 mL/h and the receiving distance was 18 cm at a voltage of 18-20 KV. The obtained electrospun fiber membranes were vacuum-dried at room temperature in 48 hours for performance testing. 2.4 Characterization The chemical structure of the AA-PEAs was recorded at room temperature using BRUKER Spectrometer operating at 400 MHz for 1H NMR spectrum with the deuterated dimethyl sulfoxide as the solvent. The water contact angles on the surface of the fiber membranes were measured using an optical contact Angle tester. The 3 μL droplet was placed on the membrane surface, and the static images of the droplets at different times were recorded. The thermal stability was determined using a TGA-Q50 thermogravimetric analyzer under the following conditions: nitrogen atmosphere, heating rate: 20℃/min, and test range: 30-700℃. The Tg was determined by using a DSC214 differential thermal scanning calorimeter under the following conditions: nitrogen atmosphere, heating rate: 20℃/min, and test range: -80-100℃. 3. Results and Discussion 3.1 1H NMR Analysis The chemical structure of the obtained AA-PEAs was characterized by 1H NMR. As shown in Figure. 2 (a), the proton peak of δ=7.26-7.10 ppm was the characteristic peak of H on the benzene ring, the chemical shift δ=7.51-7.41 ppm was the characteristic peak of H on the TosoH benzene ring, and the chemical shift δ=2.28 ppm was the characteristic peak of the methyl group on TosoH. At around 1.30 ppm and 3.95 ppm, The characteristic peaks of H on different methylene groups in 1,3- 89 propanediol appeared, implying the successful synthesis of phenylalanine propylene ester. As shown in Figure. 2 (b), the characteristic peaks of ToSOH benzene ring and the H on methyl group at chemical shifts δ=7.51-7.41 ppm and 2.28 ppm had disappeared, indicating that the ToSOH protecting group has been completely removed. In addition, a methylene characteristic peak near the amide bond in the decanoyl chloride monomer appeared at around 2.03 ppm, indicating the successful synthesis of AA-PEAs. Figure 2. The 1H NMR spectra of the polyesteramides. 3.2 Water Contact Angle Analysis The wettability of the PCL/AA-PEAs fiber membranes was presented in Figure. 3. As shown in Figure. 3 (a), the PCL had a static contact angle of 152°, indicating a certain degree of hydrophobicity. With the increase content of AA-PEAs, the static contact angle of PCL fiber membrane gradually decreased, enhancing its hydrophilicity in Figure. 3. When the addition amounts of the AA-PEAs were 20% (b), 30% (c) and 40% (d), the contact angles of PCL/AA-PEAs fiber membranes were 97.4°, 47.5° and 44.9°, respectively. In addition, Figure. 4. recorded the changes of the droplet in the fiber membranes over time. When the addition amount of AA-PEA was 20%, the contact angle gradually decreased after the droplet was added. However, when the addition amounts of AA-PEA were 30% and 40%, the contact angles rapidly reduced to 53.4°-55.3° within 30s. These results indicated that the addition of AA-PEAs effectively improved the hydrophilicity of PCL. Figure 3. The water contact angles of PCL fiber membranes with different AA-PEAs contents. 90 Figure 4. The changes of water contact angles over time. 3.3 Thermal Performances Analysis Figure 5. DSC curves of PCL/AA-PEAs fiber membranes. Table 1. The thermal performances of PCL/AA-PEAs fiber membranes. Sample Tg/℃ Tm/℃ Td5%/℃ Td10%/℃ PCL -53.0 56.6 335.12 352.03 PCL/AA-PEAs-20% 35.8 58.6 322.55 344.74 PCL/AA-PEAs-30% 34.6 55.0 320.33 337.34 PCL/AA-PEAs-40% 34.5 55.9 298.89 341.78 The relevant thermal performances were presented in Figure. 5 and Table 1. As shown in Figure. 5, the Tg of the PCL/AA-PEAs fiber membranes gradually decreased as the addition amounts of AA- PEAs. The trend of Tm change was irregular. The values of Tg for the PCL/AA-PEAs fiber membranes were 35.8℃ (20% AA-PEAs), 34.6℃ (30% AA-PEAs) and 34.5℃ (40% AA-PEAs), respectively, which were lower than the human body temperature (37℃). The values of Tm were 58.6℃ (20% AA- PEAs), 55.0℃ (30% AA-PEAs) and 55.9℃ (40% AA-PEAs), respectively, which were higher than that of the human body. This was suitable for artificial blood vessel materials. It could also be seen 91 from Table 1 that the thermal decomposition temperatures of 5% and 10% of pure PCL fiber membranes were 335.12℃ and 352.03℃, respectively. The thermal decomposition temperatures of both 5% and 10% of PCL/AA-PEAs fiber membranes decreased as the adding amount of AA-PEAs, but the thermal decomposition temperature of 5% remained above 298℃, maintaining good thermal stability. 4. Conclusion The amino acid-based polyesteramides were successfully synthesized using L-phenylalanine, 1,3- propanediol and sebacyl chloride. The hydrophilicity of the PCL fiber membranes was significantly improved after adding the AA-PEAs. With the increase content of AA-PEAs, the static contact Angle of the PCL fiber membrane gradually decreased. When the amounts of AA-PEA were 20%, 30% and 40%, the water contact angles of the PCL/AA-PEAs fiber membranes were 64.7°, 57.5° and 44°, respectively. The values of Tg for the PCL fiber membrane were in the range of 34℃-35.8℃, which were lower than the human body temperature (37℃). The thermal decomposition temperatures of both 5% and 10% of PCL/AA-PEAs fiber membranes decreased as the adding amount of AA-PEAs, but the thermal decomposition temperature of 5% remained above 298℃, maintaining good thermal stability. Acknowledgments We gratefully acknowledge the support from the Science and Technology Program of Hebei Academy of Sciences (Grant no. 24706 and Grant no. 25706) for this work. References [1] Bhadran, A.; Shah, T.; Babanyinah, G.K.; Polara, H.; Taslimy, S.; Biewer, M.C.; Stefan, M.C. Recent Advances in Polycaprolactones for Anticancer Drug Delivery. Pharmaceutics, 15, 1977 (2023). [2] Archer, E.; Torretti, M.; Madbouly, S. Biodegradable polycaprolactone (PCL) based polymer and composites. Phys. Sci. Rev.8, 4391-4414 (2023). [3] Shivakumar, C.B.; Raju, N.R.; Ramu, P.G.; Vishwanath, P.M.; Silina, E.; Stupin, V.; Achar, R.R. Synthesis, Characterization, and Enzyme Conjugation of Polycaprolactone Nanofibers for Tissue Engineering. Pharmaceutics, 17, 953 (2025). [4] Q. Yuan, J. Huang, C. Xian, J. Wu, Amino Acid- and Growth Factor-Based Multifunctional Nanocapsules for the Modulation of the Local Microenvironment in Tissue Engineering, ACS applied materials & interfaces, 13(2), 2165-2178 (2021). [5] S. Han, J. Wu, Recent Advances of Poly (ester amide) s-Based Biomaterials, Biomacromolecules, 23(5), 1892-1919 (2022). [6] R. Xie, J. Li, M. Zhao, F. Wu, Recent advances in the development of poly (ester amide)s-based carriers for drug delivery, Saudi Pharmaceutical Journal, 32(7), 102123 (2024).