A Tissue-Homologous Keratin-PBA Hydrogel Integrating Rationally Designed Nanomicelles Enables Microenvironment-Adaptive Repair of Chronic Diabetic Wounds.
A tissue-homologous, intelligently adaptive platform integrating intrinsic regenerative bioactivity with glucose-responsive therapeutic adaptability is presented, as evidenced by rapid wound closure, enhanced M2 macrophage polarization, robust neovascularization, improved collagen remodeling, and increased granulation tissue formation.
Abstract
Chronic diabetic wounds require continuous modulation of the hyperglycemia-induced pathological microenvironment. Although glucose-responsive biomaterials show promise for diabetic wound treatment, intelligent wound management with tissue specificity and multifactorial repair capacity remains urgently needed. Here, we develop a tissue-homologous, glucose-responsive hydrogel based on epidermis-derived keratin functionalized with phenylboronic acid (Keratin-PBA), which is crosslinked with oxidized sodium alginate (OSA) to form a double-network hydrogel (cOK) and integrated with bioactive nanomicelles for adaptive wound microenvironment regulation. Co-assembled nanomicelles (OA-PG NMs), composed of oleanolic acid (OA) and propyl gallate (PG), exhibit glucose-triggered release and complementary bioactivities targeting oxidative stress, inflammation, macrophage polarization, angiogenesis, fibroblast behavior, antibacterial activity, and MMP regulation. Notably, OA promotes angiogenesis via the TGR5-Akt-eNOS-NO signaling pathway. The resulting cOK@NM hydrogel enables spatiotemporally controlled nanomicelle release and significantly accelerates diabetic wound healing in vivo, as evidenced by rapid wound closure, enhanced M2 macrophage polarization, robust neovascularization, improved collagen remodeling, reduced AGEs, broad-spectrum antibacterial effects against E. coli and S. aureus, and increased granulation tissue formation. This work presents a tissue-homologous, intelligently adaptive platform integrating intrinsic regenerative bioactivity with glucose-responsive therapeutic adaptability.
This nanocomposite hydrogel integrating a bioactive carrier with a therapeutic payload to enable coordinated intervention across multiple phases of diabetic wound repair offers a promising strategy for the treatment of chronic diabetic wounds.
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.
Ze-Cai Chen, P. Luo, Lei Qin et al.· Regenerative Biomaterials· 0 citations
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.
Rui Zhang, Suk-Fei Tan, Ye Wang et al.· Frontiers in Cell and Develo...· 0 citations
Chronic wounds affect over 20% of diabetic patients, imposing substantial socioeconomic and personal burdens. The diabetic wound microenvironment is characterized by hyperglycaemia, oxidative stress, persistent inflammation, and vascular damage, which disrupt tissue homeostasis and significantly hinder healing. The development of innovative multifunctional hydrogels is essential for treating diabetic wounds within such complex microenvironments. Based on metal-organic framework nanomaterials, this study introduces a dual-network crosslinked adhesive GelNB/HAMA hydrogel incorporating magnesium ions and Quercetin-based metal-organic frameworks (denoted as MgQu@GelNB/HAMA). In vitro experiments revealed that Mg-quercetin metal-organic framework (MgQu) promotes macrophage polarization from M1 to M2 type, scavenges reactive oxygen species, and stimulates neovascularization. Photopolymerization technology is employed to solidify the hydrogel into a dressing, ensuring strong adhesion to the wound site and minimizing secondary tissue damage while facilitating sustained, controlled release of Quercetin and magnesium ions. In a dorsal wound model of diabetic mice, this in situ formed multifunctional hydrogel dressing effectively reduces excessive inflammation, enhances neovascularization, accelerates collagen tissue regeneration, and advances wound healing. By improving the pathological microenvironment of diabetes, this study presents a promising new strategy for diabetic wound repair.
Yunshu Yang, Bin Tang, Meng Zhou et al.· Materials Today Bio· 0 citations
In vitro and in vivo results demonstrate that the injectable dual-dynamic covalent hydrogel promotes macrophage polarization toward the anti-inflammatory M2 phenotype, alleviates inflammatory responses, enhances angiogenesis, and accelerates skin regeneration.
Zhao-Guo Wang, Susu Lei, Feng Lai et al.· Biomaterials Research· 0 citations
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
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