Aug 2026· Biomaterials Advances· Vol 189, pp.
215114
· 0 citations· 56 references
Medicine
TL;DR
A multifunctional nanoplatform that enables synchronous regulation of the diabetic pathological microenvironment for effective wound repair via mild photothermal therapy via mild photothermal therapy is presented.
Abstract
Diabetic wounds represent one of the most devastating complications of diabetes mellitus, characterized by delayed or non-healing outcomes arising from the complex pathological microenvironment, including vascular impairment, excessive inflammation, and persistent infection. To achieve simultaneous modulation of the multiple pathological features underlying diabetic wounds, herein we developed polydopamine nanoparticles surface-functionalized with copper-tannic acid metal-phenolic networks (PDA@Cu-TA). PDA@Cu-TA improves the photothermal conversion efficiency of pristine PDA. Benefiting from the chelating effect of Cu-TA and the strong adhesion of PDA, this composite material achieves responsive sustained release of Cu2+, which greatly elevates its biosafety. In addition, the combination of released Cu2+ and mild photothermal treatment exhibits outstanding antibacterial capacity and markedly facilitates neovascularization. In vitro studies demonstrated that PDA@Cu-TA exhibited excellent antioxidant, anti-inflammatory, pro-angiogenic, and antibacterial activities, along with outstanding biocompatibility.In vivo experiments further confirmed that PDA@Cu-TA significantly accelerated wound closure in diabetic mice.Collectively, this study presents a multifunctional nanoplatform that enables synchronous regulation of the diabetic pathological microenvironment for effective wound repair via mild photothermal therapy.
This work developed a synergistic single-platform strategy for precise regulation of diabetic wound microenvironments, providing a promising therapeutic alternative for refractory diabetic wound treatment.
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
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
In diabetic wounds, diverse reactive oxygen species (ROS) intertwine to form a complex oxidative stress network, directly causing damage to cells and tissues. Most single-therapy materials fail to fully regulate this complex oxidative stress microenvironment, hindering wound healing. In this study, a nanozyme-hydrogel composite system was constructed. Through the complementarity of photothermal and enzyme-catalytic functions, cellular functions were enhanced while the oxidative stress microenvironment of diabetic wounds was alleviated, thereby collectively promoting wound healing. A cerium oxide (CeO2)-based nanozyme with abundant oxygen vacancies and high photothermal efficiency was fabricated via gadolinium (Gd) doping and platinum (Pt) nanocluster modification. Gd doping enhanced the catalase (CAT) -mimetic activity by increasing oxygen vacancies, while Pt nanoclusters enabled photothermal conversion. Through this functional complementarity, efficient wound regulation was achieved. To ensure stable retention, the nanozyme (GCP) was loaded into an in situ photo-cross-linkable hydrogel to form the GCP@PG dressing. In vitro and in vivo, GCP@PG scavenged intracellular ROS and promoted angiogenesis. In diabetic rats with full-thickness skin defects, the wound closure rate reached 97.95% on day 14. By integrating the functional complementarity of enzyme catalysis and photothermal effects, this composite system provides a strategy for diabetic wound repair.
Yang Yang, Dinping She, Shuya Zhang et al.· Chemistry of Materials· 0 citations
Diabetic chronic wounds remain a leading cause of non-traumatic lower-extremity amputation, driven by four concurrent pathological processes: multidrug-resistant bacterial infection, excessive reactive oxygen species (ROS), sustained pro-inflammatory macrophage polarization, and impaired neovascularization. Conventional wound dressings address only one or two of these processes, and no single-target approach can interrupt this self-reinforcing pathological network. To address this limitation, we designed TAZNP/ADH-OHA Gel, a ROS/pH dual-responsive composite hydrogel dressing. Mesoporous silica nanoparticles (MSNs) were co-loaded with the antimicrobial peptide Pexiganan (AMP, EE% = 90.10%) and Zn2+ (EE% = 33.71%), then coated with a tannic acid-Zn2+ metal-phenolic network (TA-Zn2+ MPN) to form TAZNP nanoparticles, which were subsequently embedded in a dynamically crosslinked ADH-HA/OHA hydrazone hydrogel matrix. The resulting scaffold exhibited interconnected macroporosity, stable viscoelastic properties (G′ > G″, 0.1–10 Hz), a yield strain of ∼175%, tissue adhesion of 3.97 kPa, and an equilibrium swelling ratio of 250–300%. Cumulative AMP release increased from 69.10% under physiological conditions (pH 7.4) to 94.93% under combined diabetic wound conditions (pH 6.0 + 10 mM H2O2 + 25 mM glucose), with Zn2+ reaching 86.41% under identical conditions. Early-stage kinetic analysis further demonstrated highly synchronized AMP/Zn2+ release, with apparent release-rate ratios ranging from 1.05 to 1.22 across the tested microenvironments. In vitro assays demonstrated effective antibacterial and anti-biofilm activity against S. aureus and E. coli, with TAZNP/ADH-OHA Gel outperforming free TAZNP and ADH-OHA Gel alone. The composite hydrogel protected HSFs and HUVECs against high-glucose cytotoxicity, restored HSF wound closure from 37.44% to 70.79%, and rescued HUVEC tube formation, restoring total tube length from 5615.88 µm to 15 486.40 µm and number of segments from 26.68 to 249.33. In LPS-stimulated RAW264.7 macrophages, iNOS and TNF-α mRNA were reduced to 0.59-fold and 0.61-fold, while Arg-1 and IL-10 were elevated to 4.13-fold and 5.12-fold. Flow cytometry confirmed genuine M1-to-M2 phenotypic switching, with the M1 proportion reduced from 60.61% to 25.92% and the M2 proportion increased from 35.11% to 75.44%. These results demonstrate that TAZNP/ADH-OHA Gel integrates microenvironment-responsive synchronized co-delivery with antibacterial, antioxidant, pro-angiogenic, and immunomodulatory activities, providing a promising multifunctional platform for diabetic wound management.
Severe microenvironmental imbalance in diabetic wounds infected with drug-resistant bacteria, a clinically prevalent issue yet often overlooked as a distinct pathological entity, results in a lack of coordinated multidimensional regulation of the wound microenvironment, which remains largely underexplored in current studies. Herein, we report a pH/ROS-responsive multifunctional hydrogel (G@Ru) incorporating RuNPs. G@Ru is constructed via dynamic Schiff base and boronate ester linkages, which endow it with dual stimulus responsiveness, injectability, adhesiveness, self-healing, and hemostatic properties. In addition, the intrinsic antibacterial activity of RuNPs enables the inhibition of methicillin-resistant Staphylococcus aureus. Furthermore, in vivo studies confirm that G@Ru can regulate macrophage polarization, modulate reactive oxygen species levels, enhance cell proliferation, stimulate angiogenesis, and accelerate tissue regeneration, thereby reshaping the wound microenvironment in a multidimensional manner. Ultimately, G@Ru exhibits superior therapeutic efficacy, achieving a wound closure rate of 98% in infected diabetic wounds by day 14, highlighting its antibiotic-free therapeutic potential and promising clinical translational applications.
Rongrong Li, Shangbo Zhang, Zan Wang et al.· Biomacromolecules· 0 citations
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