A precision-engineered hydrogel that integrates structural integrity with environment-triggered delivery and seamlessly coupling nanocontrolled release with microenvironmental sensing is presented, presenting a precision-engineered platform for the synergistic treatment of recalcitrant diabetic wounds.
Abstract
Infected diabetic wounds are complicated by bacterial infection, oxidative stress, and hyperglycemia, limiting conventional monotherapies. Combination therapies suffer from uncontrolled release and poor responsiveness to pathological cues. Here, we report a nanoparticle-cross-linked hydrogel that integrates structural integrity with environment-triggered delivery. We utilized self-assembled epigallocatechin gallate (EGCG)-tobramycin (TOB) nanoparticles as dynamic cross-linkers within a phenylboronic acid-modified gelatin network. The engineered system provides dual-stage responsiveness: the hydrogel disassembles under the hallmark hyperglycemic and acidic conditions of diabetic wounds, releasing the nanoparticles, which then dissociate under acidity to synchronize drug release. Such sequential disassembly acts as a synergistic "one-two punch," allowing EGCG to scavenge ROS and remodel the inflammatory microenvironment, while TOB provides prolonged antibacterial action. In vivo, the system significantly reduced bacterial load, accelerated epithelial regeneration, and promoted high-quality wound healing. By seamlessly coupling nanocontrolled release with microenvironmental sensing, we present a precision-engineered platform for the synergistic treatment of recalcitrant 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.
Yuefei Zhu, Na Yan, Yongqiang Xiao et al.· Small· 0 citations
Persistent bacterial infection, oxidative stress imbalance, and cellular dysfunction within diabetic wound microenvironments represent key clinical challenges that hinder wound healing. To address these challenges, we developed a smart reactive oxygen species (ROS)-responsive bilayer thermoregulatory hydrogel, PP@PZC&SAg. The system was based on a dynamically cross-linked phenylboronate ester network. The in situ green synthesis of Ag nanoparticles endowed the hydrogel with highly efficient photothermal bactericidal capabilities, whereas the incorporated Zn/Ce layered double oxide nanozyme (PZC) mimicked catalase activity to scavenge excess ROS in the microenvironment. The top layer comprised a thermosensitive hydrogel that utilized its phase-change properties to precisely regulate photothermal temperatures, thereby effectively destroying bacterial biofilms while preventing thermal damage to surrounding tissues. The PP@PZC&SAg hydrogel system exhibited considerable photothermal activity, rapidly reaching and maintaining a stable operating temperature while simultaneously eliminating bacteria and disrupting biofilms. Furthermore, 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. This approach simultaneously combats bacterial infections, alleviates oxidative stress, and restores cellular function, thereby offering a novel, multifaceted, and targeted therapeutic strategy for treating diabetic wounds.
Songjie Li, Han Chen, Xin Dan et al.· Nano Reseach· 0 citations
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.
Xihao Wang, Jingting Huang, Chuipin Kong et al.· ACS Applied Materials and In...· 0 citations
Diabetic ulcers pose significant therapeutic challenges driven by hyperglycemia-induced oxidative stress, chronic inflammation, and microbial infection. While conventional dressings often fail to address these complex microenvironments, hydrogels have emerged as a premier platform for advanced wound management. Among these, chitosan-based hydrogels stand out for their intrinsic antimicrobial activity, biocompatibility, and tunable properties, enabling active orchestration of wound healing. Their therapeutic effects involve neutralizing oxidative stress, polarizing macrophages to resolve inflammation, and promoting angiogenesis for extracellular matrix remodeling. Moreover, these hydrogels can serve as multifunctional, stimuli-responsive platforms for the controlled delivery of drugs, growth factors, extracellular vesicles, nucleic acids, and even living cells, allowing precise spatiotemporal control of cargo release. This review summarizes the physicochemical properties of chitosan and systematically examines the molecular mechanisms underlying hydrogel-mediated diabetic wound repair. These include cation-mediated disruption of microbial membranes, Keap1/Nrf2-dependent antioxidant signaling, NF-κB-regulated immunomodulation, and VEGF-driven angiogenic pathways. In parallel, recent advances are critically evaluated in three key areas: stimuli-responsive delivery systems (triggered by pH, reactive oxygen species, matrix metalloproteinases, or glucose), biologically functionalized scaffolds incorporating extracellular vesicles, microRNAs, and stem cells, and 3D-bioprinted constructs tailored to individual patients. Current translational challenges are also addressed, particularly the complexity of regulatory classification and the lack of standardized preclinical models. Finally, future strategies are discussed for the rational design and clinical translation of next-generation diabetic wound dressings, with an emphasis on bridging the gap between bench research and bedside application.
Hongyun Chen, Ying Xin, Cheng-Kun Liu et al.· International Journal of Bio...· 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
