Aug 2026· Biomaterials Science· 0 citations· 28 references
Medicine
TL;DR
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.
Abstract
The refractory healing of diabetic wounds represents a major clinical challenge, primarily attributed to a vicious cycle formed by persistent bacterial infection, excessive oxidative stress, and a dysregulated immune microenvironment. To simultaneously address multiple pathological barriers, an intelligent composite nanoplatform was designed and constructed in this study, integrating near-infrared (NIR) photothermal therapy, reactive oxygen species (ROS) scavenging, antimicrobial activity, and immunomodulation. A mesoporous polydopamine (MPDA) core was loaded with chlorogenic acid (CGA), a natural antioxidant, and further coated with a copper-zinc bimetallic organic framework (Cu/Zn-MOF) to fabricate Cu/Zn-MOF@CGA@MPDA NPs, exhibiting pH-responsive dissociation in the acidic infected wound microenvironment. Under 808 nm near-infrared irradiation, the fabricated NPs showed excellent photothermal performance, efficiently eliminating bacteria and biofilms in vitro. They also scavenged ROS to relieve oxidative damage and promoted macrophage polarization from the pro-inflammatory M1 to pro-healing M2 phenotype. In a diabetic rat model of infected full-thickness skin wounds, the nanoplatform achieved antibacterial and anti-inflammatory effects simultaneously. Such synergistic functions promoted collagen deposition and re-epithelialization, thereby accelerating diabetic wound healing. Histological and hematological tests verified its good biocompatibility and biosafety. 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 diabetic wounds represent a severe complication of diabetes mellitus and a prototypical form of chronic nonhealing wounds, characterized by biofilm-associated infection, persistent inflammation, and impaired angiogenesis. Herein, a multifunctional microneedle platform incorporating cationic chitosan-coated ruthenium dioxide nanozymes (RuO2@QCS NPs), termed RuO2@QCS-MN, is developed to accelerate diabetic wound healing through microenvironment reprogramming. This integrated system combines photothermal antibacterial activity, reactive oxygen species (ROS) scavenging, and in situ oxygen generation to coordinately regulate the pathological milieu of infected wounds. The microneedles effectively penetrate bacterial biofilms and deliver nanozymes to bacteria-enriched regions, enabling efficient yet mild photothermal antibacterial therapy. Meanwhile, RuO2@QCS NPs exhibit catalase-like activity, catalyzing endogenous hydrogen peroxide into oxygen, thereby enhancing nanozyme diffusion, alleviating oxidative stress, modulating inflammatory responses, and promoting macrophage polarization. Simultaneous oxygen generation may alleviate hypoxia and promote angiogenic responses. Both in vitro and diabetic in vivo models demonstrate efficient bacterial elimination, inflammation suppression, and enhanced re-epithelialization and neovascularization, ultimately accelerating wound repair. This work establishes a highly integrated nanozyme-enabled therapeutic paradigm for the localized treatment of infected diabetic wounds.
Xiang Li, Yuemiao Mao, Bo Ye et al.· ACS Applied Materials and In...· 0 citations
This work demonstrates a safe and effective strategy for combating MDR infections through the combined action of photothermal therapy and nanozyme catalysis, offering promising potential for clinical wound management.
Weiwei Zhang, Lixiang Fan, Xuanjun Zhang et al.· ACS Applied Materials and In...· 0 citations
Chronic bacterial infections and oxidative stress severely impede wound healing, necessitating innovative strategies that simultaneously eradicate pathogens and modulate the hostile wound microenvironment. Herein, we develop a near-infrared (NIR)-responsive multifunctional nanoplatform (APDA-Pt) by integrating l-arginine-assisted polydopamine (APDA) with catalase-mimetic platinum nanoparticles (Pt NPs) to achieve synergistic photothermal antibacterial therapy and oxidative stress regulation. APDA serves as both a robust photothermal transducer and a versatile scaffold to anchor ultrasmall Pt NPs with high dispersion and enhanced catalytic utilization. Under NIR irradiation, APDA-Pt rapidly elevates local temperature, enabling efficient membrane disruption and broad-spectrum antibacterial efficacy (>99% inactivation of E. coli and S. aureus). Meanwhile, Pt NPs exhibit catalase-mimetic activity by catalyzing the decomposition of H2O2 into H2O and O2, whereas the APDA framework provides intrinsic antioxidant activity through its redox-active catechol groups, thereby synergistically alleviating oxidative stress. In an S. aureus-infected murine wound model, APDA-Pt combined with NIR irradiation markedly accelerates wound closure (≈90% by day 10), reduces bacterial burden by over 4 orders of magnitude, and promotes collagen deposition and tissue regeneration, without inducing systemic toxicity. This work presents an externally triggered multifunctional therapeutic platform that integrates photothermal bacterial eradication with antioxidant regulation, providing a promising strategy for chronic wound management.
Skin wounds are highly susceptible to bacterial invasion, and persistent infection remains a major obstacle to effective tissue repair. Conventional wound dressings often show insufficient antibacterial activity and limited capacity to actively regulate the infected wound microenvironment. Herein, an acid-responsive nanozyme-loaded composite fibrous membrane was developed as a non-antibiotic wound dressing for enhanced chemodynamic antibacterial therapy. Silver nanocubes were encapsulated within zeolitic imidazolate framework-67 to form Ag@ZIF-67 nanozymes, which were subsequently incorporated into electrospun polycaprolactone fibers to obtain Ag@ZIF-67/PCL composite membranes. Under weakly acidic conditions mimicking infected wounds, the ZIF-67 shell underwent microenvironment-triggered decomposition, enabling sustained release of Co2⁺ and Ag⁺. The released Co2⁺ catalyzed the conversion of H₂O₂ into highly toxic hydroxyl radicals through a Fenton-like reaction, while Ag⁺ provided additional broad-spectrum antibacterial activity. Benefiting from this complementary antibacterial mechanism and the extracellular matrix-like fibrous architecture, the Ag@ZIF-67/PCL membrane achieved antibacterial efficiencies exceeding 98% against both Escherichia coli and Staphylococcus aureus after 48 h. Moreover, the composite membrane exhibited favorable cytocompatibility and hemocompatibility, promoted endothelial cell migration, and significantly accelerated the healing of S. aureus-infected wounds in vivo by enhancing re-epithelialization, collagen deposition, and neovascularization. Overall, this study provides a pH-responsive, nanozyme-integrated fibrous membrane with combined antibacterial and pro-regenerative functions, offering a promising strategy for the treatment of bacteria-infected wounds without relying on antibiotics.
Han Lin, Jingyan Huang, Xiaoqi Xie et al.· Colloids and Surfaces B: Bio...· 0 citations
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.
Juan Wang, Wei Liu· Biomaterials Advances· 0 citations
Rationale : Chronic diabetic wounds are complicated by multidrug-resistant (MDR) infections and a deleterious oxidative microenvironment, rendering single-target therapies ineffective. This study aimed to develop a smart, dual-metal-organic framework (MOF) nanoplatform (PCNZnCy) capable of microenvironment-responsive, coordinated antibacterial, antioxidant, and pro-regenerative therapy for infected diabetic wounds. Methods : The nanoplatform PCNZnCy was constructed by integrating the natural flavonoid chrysin into a zinc-doped porphyrinic MOF (PCN-224), enabling pH-and reactive oxygen species (ROS)-triggered co-release of Zn² ⁺ and chrysin. Antibacterial and anti-biofilm activity was assessed against biofilm-embedded MDR pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA). Antioxidant and signaling effects were evaluated by measuring ROS scavenging, mitochondrial function, endothelial cell proliferation, and activation of Nrf2/HO-1, STAT3, and Akt pathways, with confirmation using the Nrf2 inhibitor ML385. To assess efficacy and safety in a clinically meaningful setting, we used a diabetic murine wound model infected with P. aeruginosa and a systems-level transcriptomic analysis to capture the broader tissue response. Results : We found that PCNZnCy showed strong synergistic antibacterial activity against MRSA and PA. Beyond that, it scavenged excess ROS, triggered Nrf2/HO-1 signaling, modulated STAT3 and Akt signaling, preserved mitochondrial health, and spurred endothelial cell growth. In diabetic mice, wounds healed faster, with improved collagen deposition and increased formation of new blood vessels, while the compound remained safe. RNA-seq data underscored a decisive move from pro-inflammatory to pro-regenerative gene expression. Conclusions : PCNZnCy adapts to the wound's specific microenvironment, enabling it to kill bacteria, reduce oxidative stress, and promote tissue regeneration. In the infected diabetic models, it worked consistently well. This makes it a strong candidate for multifactorial, complex wound pathologies, in which multiple complications overlap.
Yipeng Pang, F. M. Amona, Hanyuan Liu et al.· Theranostics· 0 citations