AB4-Loaded Nanomicelle Hydrogel Promotes Targeting of the Dysregulated Diabetic Wound Microenvironment via Coordinated Multistage Repair

Biomaterial-mediated remodelling of the inflammatory microenvironment: a pH/ROS-responsive EGCG–metformin hydrogel for infected diabetic wound regeneration

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.

Naringin-based hydrogel decorated 3D printed scaffold modulates immunity and angiogenesis for diabetic bone regeneration

Hyperglycemia and inflammation within the diabetic microenvironment impair the healing of bone defects in diabetic patients. A key limitation of current therapeutic approaches is their lack of efficacy in restoring immune homeostasis. Herein, a novel 3D-printed PHSN composite scaffold is designed to regulate the immune microenvironment. PHSN is fabricated by integrating poly (lactic-co-glycolic acid) (PLGA) with hydroxyapatite (HA) via 3D printing technology, yielding a structure that combines osteogenic potential with mechanical strength. Loaded with naringin and SupGels, PHSN promotes macrophage repolarization toward the M2 phenotype via the JAK/STAT signaling pathway, thereby upregulating anti-inflammatory mediators and tissue-regeneration factors, stimulating angiogenesis and osteogenesis. In diabetic models, PHSN inhibits M1 macrophage polarization, drives reprogramming toward the M2 phenotype, and upregulates the expression of CD31, ALP, and OCN at bone defect sites, indicating enhanced angiogenesis and osteogenesis. Collectively, this study establishes a strategy of synergistically modulating immunity, vascularization, and bone formation, offering a promising and translatable solution for diabetic bone regeneration.

Hydrogel microneedles loaded with engineered extracellular vesicles accelerate diabetic wound healing by promoting angiogenesis and modulating macrophage polarization

Oxidative stress, impaired angiogenesis, and persistent inflammation contribute to delayed diabetic wound healing. In this study, ALDH2-loaded liposomes were associated with extracellular vesicles derived from human amniotic mesenchymal stem cells to generate an ALDH2@Lipo/EV hybrid formulation, which possess pro-angiogenic, antioxidant, and anti-inflammatory properties that modulate mitochondrial homeostasis in cells within diabetic wounds. To enhance the penetration efficiency of EVs in the wound, ALDH2@Lipo/EV were loaded into methacrylated gelatin (GelMA) hydrogel to fabricate the ALDH2@Lipo/EV-MN patch system. The microneedles technology enabled precise and efficient delivery of ALDH2@Lipo/EV, ensuring an optimal depth of delivery for maximum therapeutic efficacy. Mechanistically, ALDH2@Lipo/EV promoted angiogenesis in vitro and alleviated oxidative damage and inflammation in macrophages by inhibiting the activation of dynamin-related protein 1 (Drp1) and activating the PINK1/Parkin signaling pathway. Furthermore, the ALDH2@Lipo/EV-MN patch was shown to enhance diabetic wound healing in a mouse model. This study explored the functions and mechanisms of the ALDH2@Lipo/EV-MNs system, providing a new strategy for the treatment of refractory diabetic wounds.

Multifunctional Polyphenol-Polymer Nanocomposite Hydrogel Targeting Inflammation, Oxidative Stress, and Infection in Diabetic Wounds.

A multifunctional, mechanism-targeted strategy that provides a rational, disease-relevant approach for treating chronic diabetic wounds by dampening inflammatory signaling and protecting reparative cells is developed.

Multifunctional Intelligent Hydrogels Based on MnO2 Nanozymes and Ca2+ Signal Regulation for Diabetic Wound Repair

Diabetic refractory wounds are a prevalent and severe complication of diabetes, whose pathological progression is jointly mediated by multiple factors, including oxidative stress imbalance, chronic inflammation, impaired angiogenesis, bacterial infection, and biofilm formation. Current clinical hydrogel dressings generally suffer from drawbacks such as single-function performance, potential toxicity of nano-components, static networks incompatible with dynamic wound conditions, and the absence of bionic repair signals. Therefore, they cannot simultaneously satisfy the dual repair requirements of complex pathological microenvironments and dynamic mechanical properties for diabetic wounds. In this study, a multi-functional dynamically responsive composite hydrogel (MC group) with high-efficiency antioxidant, antibacterial, and pro-angiogenic capacities was fabricated. Using SDS-C18 micelles as hydrophobic units, a rigid–flexible dual-network framework was constructed with polyvinyl alcohol (PVA) and methacrylated hyaluronic acid (HAMA). Manganese dioxide nanozymes were introduced to scavenge reactive oxygen species (ROS) and mitigate oxidative stress. Calcium-ion-mediated dynamic micelle reconstruction was adopted to regulate the hydrophilic–hydrophobic balance, while achieving antibacterial effects and facilitating tissue regeneration. In vitro experiments verified that the MC hydrogel possesses mechanical properties well-matched to human soft tissues (fracture stress: 25 kPa) and excellent biocompatibility (cell viability > 100%, hemolysis rate: only 0.13%). It also exhibits prominent antioxidant activity (DPPH radical-scavenging rate: 36.95%), antibacterial performance (>99.86% bactericidal rate against Staphylococcus aureus, survival rate of Escherichia coli reduced to 15.95%), and cell-migration-promoting activity (endothelial cell migration rate of 83.72% and mouse fibroblast migration rate of 90.88% within 24 h). In the full-thickness skin defect model of diabetic mice, the wound-healing rate reached 99% on day 16. Moreover, it promoted ordered collagen deposition, skin appendage regeneration, and functional microvascular reconstruction, thereby accomplishing high-quality tissue repair. This design synergistically intervenes in multiple pathological links of diabetic wounds, overcomes several key limitations of existing dressings, and provides an innovative strategy for developing smart dressings.

A dual-targeted oligonucleotide delivery hydrogel for diabetic wound healing: Regulating macrophage-endothelial crosstalk and ferroptosis.