Hydrogel-forming microneedles with epigallocatechin gallate and 4-(hydroxymethyl)-phenylboronic acid for antibacterial wound healing and drug release
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Abstract
Wounds in diabetic patients represent a major therapeutic challenge, necessitating advanced treatment strategies with sustained drug delivery and infection control. This research introduces a hydrogel-based microneedle dressing incorporating epigallocatechin gallate (EGCG) and 4-(hydroxymethyl)-phenylboronic acid (HPBA), focusing on the crosslinking interactions that govern their structural, mechanical, and functional performance. Among the tested formulations, the hydrogel containing EGCG and HPBA in a 1:1 ratio exhibited the greatest swelling ability, which was likely due to its efficient capacity to retain water. Meanwhile, the HPBA-only hydrogel showed the lowest swelling ability due to its dense polymer network. The 1:1 formulation also exhibited superior mechanical strength and flexibility, enabled by efficient crosslinking that enhanced structural integrity. Drug release studies revealed that the EGCG-HPBA (1:2) hydrogel allowed for rapid initial drug release, while the 1:1 formulation provided a slower, sustained release profile, making it more suitable for controlled drug delivery. Moreover, EGCG demonstrated significant bactericidal activity toward E. coli and S. aureus, and this activity was retained upon integration with HPBA. The results demonstrate that the EGCG-HPBA (1:1) hydrogel microneedle system is a promising multifunctional dressing for chronic wound management, combining mechanical resilience, controlled drug release, and antibacterial efficacy.
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References
Guan Z, Li H, Liu R, Cai C, Liu Y, Li J. Artificial intelligence in diabetes management: Advancements, opportunities, and challenges. Cell Rep Med. 2023;4(10):101213.
Hossain MJ, Al-Mamun M, Islam MR. Diabetes mellitus, the fastest growing global public health concern: Early detection should be focused. Health Sci Rep. 2024;7(3): e2004.
Mieczkowski M, Rakowska BM, Kowara M, Kleibert M, Czupryniak L. The problem of wound healing in diabetes—from molecular pathways to the design of an animal model. Int J Mol Sci. 2022;23(14). 7930.
Nagle DG, Ferreira D, Zhou YD. Epigallocatechin-3-gallate (EGCG): Chemical and biomedical perspectives. Phytochemistry. 2006;67(17):1849–1855.
Zhu T, Li M, Zhu M, Liu X, Huang K, Li W, et al. Epigallocatechin-3-gallate alleviates type 2 diabetes mellitus via β-cell function improvement and insulin resistance reduction. Iran J Basic Med Sci. 2022;25(4):483-488.
Isbrucker RA, Bausch J, Edwards JA, Wolz E. Safety studies on epigallocatechin gallate (EGCG) preparations. Part 1: Genotoxicity. Food Chem Toxicol. 2006;44(5):626–635.
Lambert JD, Yang CS. Mechanisms of cancer prevention by tea constituents. J Nutr. 200;133(10). 3262S 3267S.
Aguirre-Chagala YE, Santos JL, Huang Y, Herrera-Alonso M. Phenylboronic acid-installed polycarbonates for the pH-dependent release of diol-containing molecules. ACS Macro Lett. 2014;3(12):1249–1253.
Ma R, Shi L. Phenylboronic acid-based glucose-responsive polymeric nanoparticles: synthesis and applications in drug delivery. Polym Chem. 2014;5(5):1503–1518.
Matsumoto A, Yoshida R, Kataoka K. Glucose-responsive polymer gel bearing phenylborate derivative as a glucose-sensing moiety operating at the physiological pH. Biomacromolecules. 2004;5(3):1038–1045.
Brooks WLA, Sumerlin BS. Synthesis and applications of boronic acid-containing polymers: From materials to medicine. Chem Rev. 2016;116(3):1375–1397.
Sapuła P, Bialik-Wąs K, Malarz K. Are Natural Compounds a Promising Alternative to Synthetic Cross-Linking Agents in the Preparation of Hydrogels? Pharmaceutics. 2023;15(1).253-255.
Lyu S, Dong Z, Xu X, Bei HP, Yuen HY, James Cheung CW, et al. Going below and beyond the surface: Microneedle structure, materials, drugs, fabrication, and applications for wound healing and tissue regeneration. Bioact Mater. 2023;27:30-33.
Qin Y, Qiu C, Hu Y, Ge S, Wang J, Jin Z. In situ self-assembly of nanoparticles into waxberry-like starch microspheres enhanced the mechanical strength, fatigue resistance, and adhesiveness of hydrogels. ACS Appl Mater Interfaces. 2020;12(41):46609–46620.
Wang D, Kim D, Shin CH, Zhao Y, Park JS, Ryu M. Evaluation of epigallocatechin gallate (EGCG) to remove Pb(II) using spectroscopic and quantum chemical calculation method. Environ Earth Sci. 2019;78(5):1–8.
Bai Z, Dan W, Yu G, Wang Y, Chen Y, Huang Y. Tough and tissue-adhesive polyacrylamide/collagen hydrogel with dopamine-grafted oxidized sodium alginate as crosslinker for cutaneous wound healing. RSC Adv. 2018;8(73):42123–42132.
Reichelt R, Schmidt T, Kuckling D, Arndt KF. Structural characterization of temperature-sensitive hydrogels by field emission scanning electron microscopy (FESEM). Macromol Symp. 2004;210:501–511.
Jorgensen JH, Ferraro MJ. Antimicrobial susceptibility testing: A review of general principles and contemporary practices. Clin Infect Dis. 2009;49(11):1749–1755.
Zhao X, Pei D, Yang Y, Xu K, Yu J, Zhang Y. Green Tea Derivative Driven Smart Hydrogels with Desired Functions for Chronic Diabetic Wound Treatment. Adv Funct Mater. 2021;31(18):2009442.
Dahiya S, Rani R, Kumar S, Dhingra D, Dilbaghi N. Chitosan-gellan gum bipolymeric nanohydrogels—a potential nanocarrier for the delivery of epigallocatechin gallate. Bionanoscience. 2017;7(3):508–520.
Shen D, Yu H, Wang L, Chen X, Feng J, Li C, et al. Glucose-responsive hydrogel-based microneedles containing phenylborate ester bonds and N-isopropylacrylamide moieties and their transdermal drug delivery properties. Eur Polym J. 2021;148:110348.
Liu F, Li G, An Z, Wang S, Xu S, Liu H. Dynamic boronate ester based hydrogel with enhanced mechanical properties and multi-stimuli-triggered release for tissue repair and antioxidant therapy. Gels. 2025;11(5):370-375.
Terriac L, Helesbeux JJ, Maugars Y, Guicheux J, Tibbitt MW, Delplace V. Boronate ester hydrogels for biomedical applications: Challenges and opportunities. Chem Mater. 2024;36(14):6674–6695.
Wang Q, Wang S, Chen M, Wei L, Dong J, Sun R. Anti-puncture, frigostable, and flexible hydrogel-based composites for soft armor. J Mater Res Technol. 2022;21:2915–2925.
He Z, Luo H, Wang Z, Chen D, Feng Q, Cao X. Injectable and tissue adhesive EGCG-laden hyaluronic acid hydrogel depot for treating oxidative stress and inflammation. Carbohydr Polym. 2023;29:1-9.
Huang J, Fu P, Li W, Xiao L, Chen J, Nie X. Influence of crosslinking density on the mechanical and thermal properties of plant oil-based epoxy resin. RSC Adv. 2022;12(36):23048–23056.
Han Y, Cao Y, Lei H. Dynamic covalent hydrogels: Strong yet dynamic. Gels. 2022;8(9):565-577.
Hernández-Ortiz JC, Vivaldo-Lima E, 7th editors. Handbook of Polymer Synthesis,Characterization, and Processing. Wiley. 2013;10:187–204.
Raina N, Pahwa R, Bhattacharya J, Paul AK, Nissapatorn V, Pereira M, de L. Drug delivery strategies and biomedical significance of hydrogels: Translational considerations. Pharmaceutics. 2022;14(3) :534-574.
Duque C, Souza ACA, Aida KL, Pereira JA, Caiaffa KS, Santos VRD. Synergistic antimicrobial potential of EGCG and fosfomycin against biofilms associated with endodontic infections. J Appl Oral Sci. 2023;31:e20220282.
Sokker HH, Abdel Ghaffar AM, Gad YH, Aly AS. Synthesis and characterization of hydrogels based on grafted chitosan for the controlled drug release. Carbohydr Polym. 2009;75(2):222–229.
Tong MQ, Luo LZ, Xue PP, Han YH, Wang LF, Zhuge DLl. Glucose-responsive hydrogel enhances the preventive effect of insulin and liraglutide on diabetic nephropathy of rats. Acta Biomater. 2021;122:111–132.
