A smart and microenvironment‐programmable PVH‐ST hydrogel is developed to achieve phased and spatiotemporally coordinated regulation of diabetic‐infected wound healing.
Abstract
The diabetic‐infected wound microenvironment, marked by elevated reactive oxygen species (ROS) levels, ongoing inflammation, and defective angiogenesis, interferes with the normal wound healing cascade and contributes to delayed and treatment‐resistant repair. However, most existing wound dressings lack the capability to dynamically adapt to these spatiotemporally evolving conditions. Herein, a smart and microenvironment‐programmable PVH‐ST hydrogel is developed to achieve phased and spatiotemporally coordinated regulation of diabetic‐infected wound healing. The hydrogel is engineered by integrating strontium (Sr)‐tannic acid (ST) nanoparticles into a polyvinyl alcohol (PVA) and hyaluronic acid (HA) matrix through a boric acid‐mediated multilevel dynamic crosslinking network, endowing the system with mechanical robustness suitable for daily motion. Upon wound occurrence, the PVH‐ST hydrogel rapidly induces hemostasis and establishes a bioactive provisional matrix. In response to the ROS‐enriched infected microenvironment, the dynamic borate bonds undergo on‐demand dissociation, triggering controlled release of ST nanoparticles. Released ST nanoparticles integrate antibacterial and antioxidant functions and reduce inflammatory burden via modulation of NF‐κB signaling and skewing macrophages toward an M2 pro‐regenerative state. Concurrently, the sustained release of Sr2+ ions activates VEGF‐associated angiogenic signaling and epithelialization pathways, thereby promoting vascularization and epithelial reconstruction for diabetic‐infected wounds.
Through synergistic ROS scavenging and the release of active Zn and Ce ions, this system restored endothelial cell proliferation, migration, and tubulogenic capacity, which are typically impaired under high-glucose conditions, ultimately promoting rapid diabetic wound healing.
Songjie Li, Han Chen, Xin Dan et al.· Nano Reseach· 0 citations
Chronic wounds remain a major clinical challenge due to persistent inflammation, excessive oxidative stress, and impaired tissue regeneration. Herein, we developed a multifunctional hydrogel dressing (GX/ML) by integrating a reactive oxygen species (ROS)‐responsive dynamic borate ester cross‐linking network with electrocatalytic MXene nanosheets and anti‐inflammatory luteolin. The hydrogel enables real‐time monitoring of wound inflammation through electrochemical sensing of H2O2 levels, while on‐demand drug release is triggered by either high ROS or near‐infrared irradiation. In vitro and in vivo results demonstrated exceptional ROS‐scavenging capability, efficient antibacterial activity (>96% against S. aureus and E. coli), and promotion of macrophage polarization toward the pro‐healing M2 phenotype. In a diabetic mouse wound model, the GX/ML hydrogel accelerated wound closure (98.1% healing rate by day 19), enhanced angiogenesis, collagen deposition, and re‐epithelialization, and modulated immune responses via cytokine signaling pathways (e.g., NF‐κB and NOD‐like receptor pathways). Transcriptomic analysis confirmed regulation of genes related to immune inflammation and tissue remodeling. This work provides a synergistic strategy through a smart hydrogel platform that integrates real‐time inflammatory monitoring with condition‐triggered drug release, offering a feedback‐responsive approach for chronic wound management.
Hua Wei, Hongyu Zhao, Xiao-Han Li et al.· Aggregate· 1 citation
Healing of diabetic wounds is severely hindered by a persistent vicious cycle of bacterial infection and metabolic disorders. Pathological microenvironments, characterized by high glucose levels and excessive reactive oxygen species (ROS), exacerbate chronic inflammation and impede the transition of macrophages toward a pro-healing phenotype. To address these challenges, we developed a multi-stimuli-responsive composite hydrogel platform (GHFA/Cu@TA) by integrating fulvic acid (FA) and copper-tannic acid nanozymes (Cu@TA NPs) into a dynamic covalent network composed of methacrylated gelatin (GelMA) and phenylboronic acid-modified hyaluronic acid (HA-PBA). This platform implements a self-feedback mechanism to restore metabolic homeostasis: glucose-triggered release of Cu@TA NPs effectively scavenges microenvironmental ROS to drive tissue microenvironment remodeling, thereby decelerating responsive hydrogel degradation upon homeostasis normalization to ensure synchronized on-demand drug delivery. Intelligently released FA promotes M2 macrophage polarization to reshape the immune microenvironment, while Cu@TA NPs achieve photothermal biofilm eradication under near-infrared (NIR) light. This "metabolic sensing-feedback regulation-homeostasis reconstruction" strategy offers a distinct therapeutic framework for addressing diabetic wound and contributes to the rational design of bioactive dressings with stimuli responsiveness.
Na Yang, Lingling Tang, Huanghe Zeng et al.· International Journal of Bio...· 0 citations
In vivo studies in diabetic Sprague-Dawley rats model demonstrated that CC-pMnO2-Vet@PNAA established a coordinated immune-mechanical microenvironment, achieving rapid and scar-free wound healing.
Chronic diabetic wounds remain a major clinical challenge because persistent inflammation, hypoxia, and immune dysregulation prevent the transition of macrophages from pro‐inflammatory M1 states to pro‐regenerative M2 phenotypes. Here, we report an immunomodulatory colloidal bioink that integrates zein‐based oxygen‐generating microparticles and human mesenchymal stem cells within a porous, mechanically robust matrix for adaptive in situ bioprinting. Implemented with the autonomous, intelligent, visually guided in situ robotic bioprinting platform, this bioink enables patient‐specific deposition directly onto wound defects with high spatial conformity and stable tissue integration. Sustained oxygen release alleviates local hypoxic stress, enhances stem cell survival, and reshapes the wound microenvironment to favor regenerative immune responses. In diabetic wound models, the printed constructs promote angiogenesis, accelerate wound closure, and improve tissue regeneration. Spatial transcriptomic analysis further reveals macrophage heterogeneity across wound compartments and identifies a coordinated M1‐to‐M2 transition spatially and transcriptionally associated with the combined contribution of oxygen modulation and stem cell‐derived paracrine signaling. Together, this study establishes a therapeutic strategy that combines intelligent biomaterial design, controlled hypoxic conditioning, and adaptive robotic bioprinting to achieve precision immunomodulation and personalized regenerative treatment for chronic diabetic wounds with clinical translational potential and broad future applicability.
Seol‐Ha Jeong, Eleftheria‐Angeliki Valsami, Kitae Kim et al.· Advanced Functional Material...· 0 citations
Its unique integration of the multi-dynamic network and intrinsic bioactivity endows the hydrogel with adaptability and microenvironment-regulating capabilities, offering a promising strategy for burn wound management.
Haoping Wang, Yi Guo, Lan Zhang et al.· International Journal of Bio...· 0 citations
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