Schiff-Base Crosslinked Stretchable Multifunctional Hydrogel Enables Combined Therapy in Diabetic Wound Healing.
- 1Department of Pharmaceutics, School of Pharmacy, and Key Laboratory of Pharmacology of the State Administration of Traditional Chinese Medicine, Fourth Military Medical University, Xi'an 710032, China.
- 2Department of Pharmacy, School of Stomatology, Fourth Military Medical University, Xi'an 710032, China.
- 3Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
Abstract
Diabetic wound healing remains a challenge due to persistent oxidative stress, defective angiogenesis and bacterial infection. Herein, a multifunctional hydrogel Y/PDA@HAPLL was engineered via Schiff-base crosslinking between oxidized hyaluronic acid (OHA) and ε-poly-L-lysine (ε-PLL) and incorporating Y-27632 (Y, R-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride) and polydopamine (PDA). The formulation was optimized using response surface methodology, thus achieving rapid gelation (3.8 s), strong tissue adhesion (10 kPa) and excellent stretchability. Under 808 nm laser irradiation, Y/PDA@HAPLL exhibited stable photothermal conversion and good antibacterial activity to effectively eradicate the bacterial biofilms and achieve >99% killing of S. aureus and E. coli. In vitro, skin re-epithelialization (keratinocyte proliferation and migration) and endothelial repair (tube formation) under high glucose were promoted by Y/PDA@HAPLL. In the diabetic mice with infected wounds, Y/PDA@HAPLL significantly accelerated wound closure and tissue regeneration by combining PTT antibacterial activity, ROS scavenging, endothelial repair, angiogenesis, and re-epithelialization, while concurrently downregulating ROCK1 and p-DRP1, upregulating p-eNOS and CD31, reducing mtROS, and promoting collagen deposition and remodeling. In addition, no organ damage and hepatorenal toxicity were observed during treatment period. Taken together, Y/PDA@HAPLL provided a multifunctional paradigm for the combined therapy of infected diabetic wounds by integrating rapid gelation, PTT antibacterial activity, and regeneration promotion.
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BibTeX
@article{cai2026schiffbase,
title = {{Schiff-Base Crosslinked Stretchable Multifunctional Hydrogel Enables Combined Therapy in Diabetic Wound Healing.}},
author = {Ze-Dong Cai and Yao-Wen Zhang and Xin-Ru Zou and Jia Ju and Chao Fang and Ming-Kai Li and Bang-Le Zhang},
journal = {Journal of functional biomaterials},
year = {2026},
month = sep,
doi = {10.3390/jfb17100493},
url = {https://europepmc.org/article/MED/42930828},
note = {CC BY},
}
RIS
TY - JOUR
TI - Schiff-Base Crosslinked Stretchable Multifunctional Hydrogel Enables Combined Therapy in Diabetic Wound Healing.
AU - Ze-Dong Cai
AU - Yao-Wen Zhang
AU - Xin-Ru Zou
AU - Jia Ju
AU - Chao Fang
AU - Ming-Kai Li
AU - Bang-Le Zhang
PY - 2026
DA - 2026/09/30
JO - Journal of functional biomaterials
DO - 10.3390/jfb17100493
UR - https://europepmc.org/article/MED/42930828
AB - Diabetic wound healing remains a challenge due to persistent oxidative stress, defective angiogenesis and bacterial infection. Herein, a multifunctional hydrogel Y/PDA@HAPLL was engineered via Schiff-base crosslinking between oxidized hyaluronic acid (OHA) and ε-poly-L-lysine (ε-PLL) and incorporating Y-27632 (Y, R-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride) and polydopamine (PDA). The formulation was optimized using response surface methodology, thus achieving rapid gelation (3.8 s), strong tissue adhesion (10 kPa) and excellent stretchability. Under 808 nm laser irradiation, Y/PDA@HAPLL exhibited stable photothermal conversion and good antibacterial activity to effectively eradicate the bacterial biofilms and achieve >99% killing of S. aureus and E. coli. In vitro, skin re-epithelialization (keratinocyte proliferation and migration) and endothelial repair (tube formation) under high glucose were promoted by Y/PDA@HAPLL. In the diabetic mice with infected wounds, Y/PDA@HAPLL significantly accelerated wound closure and tissue regeneration by combining PTT antibacterial activity, ROS scavenging, endothelial repair, angiogenesis, and re-epithelialization, while concurrently downregulating ROCK1 and p-DRP1, upregulating p-eNOS and CD31, reducing mtROS, and promoting collagen deposition and remodeling. In addition, no organ damage and hepatorenal toxicity were observed during treatment period. Taken together, Y/PDA@HAPLL provided a multifunctional paradigm for the combined therapy of infected diabetic wounds by integrating rapid gelation, PTT antibacterial activity, and regeneration promotion.
SN - 2079-4983
ER -