Jul 2026· International Journal of Biological Macromolecules· Vol 374, pp.
153326
· 0 citations· 86 references
Medicine
TL;DR
In vivo experiments reveal that the hydrogel significantly accelerated wound closure via improved re-epithelialization, collagen production, and neovascularization and modulated macrophage polarization toward M2 phenotype in full-thickness wound model in streptozotocin (STZ)-induced diabetic mice, suggesting this photocrosslinked hydrogel system can serve as a promising wound dressing for hard-to-heal chronic wounds.
Abstract
Excessive oxidative stress, persistent chronic inflammation, impaired angiogenesis, and delayed extracellular matrix (ECM) remodeling contribute to the chronic non-healing of diabetic wounds, which is a major clinical challenge worldwide that decreases patients' quality of life. Herein, a novel photocrosslinked hydrogel based on gallic acid functionalized chitosan methacryloyl (GA-CSMA) and fish gelatin methacryloyl (FGelMA) was developed for diabetic chronic wound treatment without exogenous therapeutic agents to provide structural stability and intrinsic bioactivity. Quantitative pore-size analysis and bulk mechanical testing confirmed that incorporation of GA-CSMA generated a denser porous architecture and improved the compressive and tensile mechanical performance of the FGelMA-based hydrogel. In addition, the optimized hydrogel formulation showed cytoprotective effects against oxidative stress by reducing intracellular reactive oxygen species (ROS) and exhibited macrophage-associated immunomodulatory activity, as evidenced by reduced pro-inflammatory mediators and enhanced pro-healing marker expression. Furthermore, GM/G-CMIII significantly promotes the proliferation, migration and in vitro angiogenesis. In vivo experiments further reveal that the hydrogel significantly accelerated wound closure via improved re-epithelialization, collagen production, and neovascularization and modulated macrophage polarization toward M2 phenotype in full-thickness wound model in streptozotocin (STZ)-induced diabetic mice. Therefore, this photocrosslinked hydrogel system can serve as a promising wound dressing for hard-to-heal chronic wounds.
Chronic diabetic wounds are characterized by prolonged inflammation, elevated reactive oxygen species (ROS), impaired angiogenesis, and delayed healing, often leading to tissue necrosis and amputation. Conventional wound dressings rarely address oxidative stress, dysregulated inflammation, bacterial infection, and local hyperglycemia simultaneously. Here, we developed a multifunctional nanoplatform consisting of tannic acid (TA)-complexed chitosan-polyethylenimine-phenylboronic acid (CPB-TA) nanoparticles embedded within a thermoresponsive poly(N-isopropylacrylamide-co-acrylic acid) [P(NIPAm-co-AAc)] hydrogel. CPB-TA nanoparticles exhibit dual cfDNA-scavenging and antioxidant activity, sequestering cfDNA through combined cationic binding and polyphenol interactions, and reducing ROS via complementary antioxidant mechanisms, thereby dampening inflammatory signaling and protecting reparative cells. The phenylboronic acid groups reversibly capture glucose through dynamic boronate ester bonds, helping to alleviate local hyperglycemia. The hydrogel matrix is designed to be responsive to body temperature, promoting localized delivery of CPB-TA at the wound site. In vitro, CPB-TA nanoparticles promoted macrophage polarization from M1 to M2, protected endothelial cells from oxidative damage, and exhibited antibacterial activity against Escherichia coli and Staphylococcus aureus. In vivo, topical application of CPB-TA@hydrogel accelerated wound closure, enhanced re-epithelialization, and increased collagen deposition in non-infected and S. aureus-infected diabetic mouse models. This multifunctional, mechanism-targeted strategy provides a rational, disease-relevant approach for treating chronic diabetic wounds.
Yuefei Zhu, Na Yan, Yongqiang Xiao et al.· Small· 0 citations
Diabetic wound healingAC: remains challenging due to persistent inflammation, oxidative stress, and impaired macrophage polarization. Herein, a multifunctional hydrogel dressing was constructed from carboxymethyl chitosan and oxidized dextran as the dynamic network, incorporating CeO2 nanozymes for early anti-inflammatory and antioxidant effects and PLGA microspheres loaded with astragaloside IV for sustained pro-regeneration. Via Schiff base crosslinking, this hydrogel self-assembled rapidly at room temperature and adhered tightly to tissue. In vitro, the hydrogel exhibited excellent biocompatibility, potent antioxidant and anti-inflammatory activities, and promoted endothelial cell migration and angiogenesis. In a diabetic rat full-thickness wound model, this hydrogel dressing effectively reduced local inflammation, drove macrophage polarization toward the M2 phenotype, and enhanced neovascularization to accelerate wound closure. RNA sequencing further revealed that inflammatory pathways, including TNF and IL-17 signaling, were suppressed while tissue regeneration programs were activated. This stepwise therapeutic strategy offers a promising alternative for diabetic wound repair.
Xihao Wang, Jingting Huang, Chuipin Kong et al.· ACS Applied Materials and In...· 0 citations
Introduction Diabetic chronic wounds resist healing because persistent bacterial infection, excessive reactive oxygen species (ROS), unresolved pro-inflammatory responses, impaired angiogenesis, and defective tissue remodelling act simultaneously and reinforce one another. We therefore developed an injectable, microenvironment-responsive nanocomposite hydrogel, AP@EM-gel, to target these interconnected pathological processes. Methods AP@EM-gel was constructed from dopamine-grafted alginate (Alg-DA), phenylboronic-acid-modified ε-poly-L-lysine (EPBA), and co-assembled epigallocatechin gallate–metformin nanoparticles (EGCG-MET NPs). Its physicochemical properties, pH/ROS-responsive drug release, antibacterial and antioxidant activities, cytocompatibility, pro-angiogenic effects, and macrophage-modulating capacity were evaluated in vitro. Therapeutic efficacy was further assessed in a streptozotocin-induced diabetic rat model of Staphylococcus aureus-infected full-thickness wounds. Results Dynamic boronate-ester crosslinking produced a self-healing and injectable network that released approximately 73% of EGCG and 68% of metformin under combined pH 6.4 and H2O2 conditions, compared with approximately 38% and 36%, respectively, at pH 7.4. AP@EM-gel achieved antibacterial rates of approximately 93% against S. aureus and 91% against Escherichia coli, exhibited broad-spectrum radical-scavenging activity, and showed favourable cyto- and haemocompatibility. It restored VEGF and bFGF expression in oxidatively stressed endothelial cells and promoted macrophage repolarisation toward the reparative M2 phenotype. In vivo, AP@EM-gel produced near-complete wound closure by day 14 and improved bacterial clearance, re-epithelialisation, collagen organisation, angiogenesis, and inflammatory resolution compared with the commercial dressing. Discussion AP@EM-gel simultaneously interrupts infection, oxidative stress, dysregulated macrophage polarisation, and impaired angiogenesis. This pathology-responsive, multi-target hydrogel represents a promising smart dressing for infected diabetic wound regeneration.
Rui Zhang, Suk Fei Tan, Ye Wang et al.· Frontiers in Cell and Develo...· 0 citations
Findings suggest that the synthesized hydrogel (BSG‐CHI) provides a favorable microenvironment for tissue regeneration and wound management applications.
Durgesh Kumar, Suhela Tyeb, Baby Shruit Shukla et al.· MedComm – Biomaterials and A...· 0 citations
A multifunctional hydrogel patch developed by chemically modifying chitosan with N-acetylsulfonyl chloride and forming a cross-linked network with polyvinylpyrrolidone (PVP) represents a promising multifunctional dressing for the effective management of infected wounds.
Insha Kakroo, Nayeema Gull, Insha Mehraj et al.· ACS Applied Bio Materials· 0 citations
Diabetic wounds are characterized by oxidative stress, chronic inflammation, and impaired tissue regeneration under persistent hyperglycemic conditions. Herein, we report an injectable dual-dynamic covalent hydrogel fabricated from phenylboronic-acid-functionalized oxidized sodium alginate and gallic-acid-conjugated chitosan. Crosslinked via reversible Schiff base and boronate ester bonds, the hydrogel exhibits excellent injectability, self-healing capability, and structural stability. Under hyperglycemic conditions, competitive glucose binding modulates the boronate ester equilibrium and induces glucose-responsive release of galloyl-containing species. These glucose-responsive release behaviors contribute to the antioxidant, antibacterial, and immunoregulatory activities of the hydrogel. In vitro and in vivo results demonstrate that the hydrogel promotes macrophage polarization toward the anti-inflammatory M2 phenotype, alleviates inflammatory responses, enhances angiogenesis, and accelerates skin regeneration. Collectively, the phenylboronic-acid-functionalized oxidized sodium alginate and gallic-acid-conjugated chitosan hydrogel represents a multifunctional glucose-responsive biomaterial with considerable potential for diabetic wound therapy.
Zhao-Yun Wang, Susu Lei, Feng Lai et al.· Biomaterials Research· 0 citations