Jul 2026· International Journal of Biological Macromolecules· Vol 379, pp.
153778
· 0 citations· 64 references
Medicine
TL;DR
An integrated approach combining network pharmacology, molecular docking, molecular dynamics simulations, and experimental validation revealed that the therapeutic efficacy of sustained local α-MG delivery involves the modulation of the PPAR-γ pathway.
Abstract
Diabetic wounds pose a major clinical challenge owing to their complex microenvironment and persistent inflammation. To address this issue, we engineered a multifunctional, in situ photocrosslinkable composite hydrogel (CMCSMA/F127/TPGS@α-MG) to promote wound healing. To overcome the hydrophobicity of the antimicrobial agent α-mangostin (α-MG), it was first encapsulated in F127/TPGS nanomicelles. These micelles were then integrated into a methacrylated carboxymethyl chitosan (CMCSMA) matrix, enabling rapid conformal gelation upon 405 nm light irradiation. The resulting hydrogel exhibited a biphasic sustained-release profile, excellent biocompatibility, and potent contact-killing and anti-biofilm activities against Staphylococcus aureus (S. aureus). In an S. aureus-infected diabetic wound model, the hydrogel significantly accelerated wound closure, achieving 99.6% closure by day 14, and facilitated high-quality tissue regeneration characterized by complete re-epithelialization and orderly collagen deposition. Furthermore, an integrated approach combining network pharmacology, molecular docking, molecular dynamics simulations, and experimental validation revealed that the therapeutic efficacy of sustained local α-MG delivery involves the modulation of the PPAR-γ pathway. This regulatory process suppresses the NF-κB/COX-2 inflammatory axis and upregulates pro-angiogenic markers, including VEGF, CD31, and α-SMA. Collectively, this dual-action platform, which synergizes physical barrier protection with targeted molecular modulation, represents a promising translational strategy for refractory diabetic wounds.
Chronic diabetic wounds remain a major clinical challenge owing to persistent bacterial infection, prolonged inflammation, excessive exudation, and impaired tissue regeneration. Herein, an injectable thermosensitive hydrogel was developed by integrating N-[(2-hydroxy-3-trimethylammonium)propyl] chitosan chloride with aldehyde-functionalized Pluronic F127 for epidermal growth factor (EGF) delivery and diabetic wound repair. The hydrogel forms a dual-crosslinked network through temperature-induced micellization and dynamic Schiff base bonding, exhibiting rapid gelation under physiological conditions, shear-thinning behavior, and self-healing properties. In vitro, the hydrogel provides a sustained release profile of EGF exhibiting effective antibacterial activity against Gram-positive S. aureus. In vivo studies in streptozotocin-induced diabetic rats demonstrate significantly accelerated wound healing, achieving 83% wound closure within 14 days compared to 45% in the control group, along with enhanced tissue regeneration characteristics, including improved collagen deposition. This multifunctional hydrogel provides a promising strategy for diabetic wound management by integrating antibacterial potential and tissue regeneration.
It is demonstrated that the catechol-nanocellulose/chitosan polymeric hydrogel effectively overcomes adhesion, infection, and oxidative stress barriers in diabetic wound healing, making it a promising candidate for difficult-to-heal chronic ulcers.
This work demonstrates a safe and effective strategy for combating MDR infections through the combined action of photothermal therapy and nanozyme catalysis, offering promising potential for clinical wound management.
Weiwei Zhang, Lixiang Fan, Xuanjun Zhang et al.· ACS Applied Materials and In...· 0 citations
Traditional wound dressings such as gauze and bandages cannot adequately handle the complex biological features of diabetic wounds, including increased bacterial infection risk and persistent inflammation. Therefore, creating multifunctional wound dressings with diverse biological activities is an essential clinical strategy. This study developed a dual-cross-linked photopolymerizable hydrogel (Q/O/Z@B/UV) for treating MRSA-infected diabetic wounds. The hydrogel integrates a network of quaternized insect chitosan and methacrylate-oxidized konjac glucomannan with a baicalin-modified zeolitic imidazolate framework-8 nanosystem. The resulting hydrogels exhibit excellent mechanical properties, biocompatibility, degradability, hemostatic effects, and antimicrobial activity. The Z@B system further enhances antibacterial, antioxidant, and anti-inflammatory activities and also promotes cell proliferation and differentiation. In a full-thickness skin defect model using MRSA-infected diabetic rats, Q/O/Z@B/UV significantly accelerated wound closure, promoted collagen deposition, suppressed inflammatory factor expression, and enhanced angiogenesis. Overall, this multifunctional hydrogel shows great potential for treating MRSA-infected diabetic wounds.
Yingxi Li, Xiao Zhou, Ying Wang et al.· Biomacromolecules· 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
Hypoxia and bacterial infection synergistically impede skin wound healing, posing significant clinical challenges. Conventional oxygen-releasing agents and antimicrobial agents are constrained by poor biocompatibility and the emergence of drug resistance. Consequently, the development of biocompatible, non-resistance-inducing oxygen-releasing antimicrobial wound dressings is of paramount importance. This study presents a κ-carrageenan (κ-Cr)/carboxymethyl chitosan (CMCS) hydrogel wound dressing loaded with Chlorella and berberine (BBR). Chlorella facilitates stable and sustained oxygen release with excellent biocompatibility, while berberine exhibits broad-spectrum antimicrobial activity without inducing drug resistance. In vitro experiments reveal that under light conditions, the hydrogel releases a cumulative 8 mg/mL of oxygen within 8 h and reduces bacterial viability to 2%, demonstrating excellent sustained oxygen-release and antimicrobial properties. The hydrogel matrix, formed via electrostatic cross-linking of κ-carrageenan and carboxymethyl chitosan, enhances adhesive performance, endowing the dressing with outstanding mechanical properties and skin adhesiveness. In vivo studies using a rat full-thickness skin wound model demonstrate the hydrogel's remarkable wound-healing efficacy: the wound healing rate reaches 98% by day 10, highlighting the hydrogel's ability to accelerate wound repair. Overall, this multifunctional hydrogel wound dressing holds substantial promise in the field of skin wound healing and provides a promising therapeutic strategy for patients with complex healing needs.
Baoqi Ding, Susu Zhang, Wenju Jiang et al.· International Journal of Bio...· 0 citations