Biomimetic hydrogel dressings: An integrated "perception-response-repair" strategy for chronic diabetic wounds.

Collision of hydrogels, chronic wounds, and nanotechnology: A bibliometric analysis from 2009 to 2024.

Diabetic foot ulcer (DFU) is characterized by persistent inflammation, metabolic dysfunction, and impaired angiogenesis, leading to refractory chronic wounds. Here, we report an adhesive, metformin-loaded (1.0 mM) polyethylene glycol (PEG) based hydrogel (i.e., PEG/Met), constructed from equal volumes of PEG-SG (20 wt.%) and PEG-NH2 (20 wt.%), to regulate macrophage polarization and metabolism in DFU. Density functional theory (DFT) calculations and infrared spectra confirmed its crosslinking, yielding a homogeneous PEG network with strong tissue adhesion (31.4 ± 8.6 kPa) and sustained drug release till seven days (total release: 86.8 ± 0.6%). In a rat DFU model, the PEG/Met significantly accelerated wound closure (wound recovery: 91.9 ± 3.4%, which was 1.96-fold to the control), collagen deposition, M2-like macrophage infiltration, and neovascularization. Under lipopolysaccharides (LPS) or Staphylococcal protein A (SpA) induced pro-inflammatory stimulation, the PEG/Met suppressed glycolytic flux, reduced glucose uptake and consumption, yet increased adenosine triphosphate (ATP) production and restored oxygen consumption, indicating a shift from glycolysis toward oxidative phosphorylation (OXPHOS). Likewise, the PEG/Met restored mitochondrial membrane potential, reduced reactive oxygen species (ROS) accumulation, increased Egln3 expression, and decreased Hif-1α and IL-1β levels, thereby alleviating Hif-1α-driven inflammatory signaling. Pharmacologic inhibition of OXPHOS with rotenone reversed PEG/Met-induced M2 polarization and reactivated pro-inflammatory gene expression, confirming the intact mitochondrial respiration for its immunoregulatory effects. This PEG/Met hydrogel functioned as both an adhesive, drug-delivery platform and immune-metabolic modulator, effectively reprogramming macrophage phenotype and mitochondrial metabolism, which held substantial promise as a localized therapy for DFU and other chronic wounds. STATEMENT OF SIGNIFICANCE: Diabetic foot ulcer (DFU) is a leading cause of limb loss worldwide, as traditional dressings only passively cover wounds without resolving chronic inflammation caused by metabolic and immune disorders. Here, we fabricated a polyethylene glycol (PEG) based adhesive hydrogel for local metformin delivery (PEG/Met), which achieved strong tissue adhesion, biodegradability, and sustained drug release. The hydrogel reprogrammed macrophage metabolism from glycolysis to oxidative phosphorylation, thereby improving mitochondrial function, decreasing mitochondrial reactive oxygen species, enhancing Egln3-mediated Hif-1α ubiquitination, and alleviating IL-1β-mediated inflammation. This hydrogel created a pro-angiogenic microenvironment to accelerate DFU healing in vivo. By linking the clinically approved metformin, this adhesive hydrogel platform offered a translational strategy for treating DFU and other chronic wounds.

Advancing preclinical research with reconstructed in vitro skin models mimicking non-healing wounds.

Chronic diabetic wounds represent a major global health challenge due to their persistent and difficult-to-heal nature, imposing substantial burdens on patients. Moist exposed burn ointment (MEBO), a traditional Chinese medicine preparation, has shown therapeutic potential in treating diabetic wounds; however, its underlying mechanisms remain to be fully elucidated. In this study, MEBO and recombinant bovine basic fibroblast growth factor (rb-bFGF), used as a positive control, were applied to diabetic rat wound models. Wound pathology, ultrastructures, and protein expression profiles were subsequently evaluated. The results demonstrated that MEBO reduced the expression of the inflammatory factors iNOS and IL-6, thereby alleviating inflammatory cell infiltration, while simultaneously increasing the expression of IL-10 and Arg1. Furthermore, MEBO enhanced the expression of ADAM-10 and p-AKT, promoting cell regeneration and increasing collagen deposition. It also elevated Beclin1 expression while reducing GRP78 and CTSK levels, suggesting improved subcellular structural integrity through the regulation of autophagy-related pathways. Notably, MEBO modulated angiogenesis via CD31 expression, thereby accelerating the wound healing process. In conclusion, MEBO significantly promotes wound healing in diabetic rats by regulating inflammatory responses, enhancing cell regeneration, regulating autophagy, facilitating collagen deposition, and promoting angiogenesis.

Collagen-oxidized hyaluronic acid injectable self-healing hydrogel enabling sequential platelet-rich plasma release for microenvironment modulation in diabetic wound repair.

MMP-9-responsive bFGF/FGF21 patch synergistically piloting the immune remodeling and regeneration of diabetic wounds.

Dynamically responsive hydrogel with mechanical stimulation enhances diabetic wound healing via activation of Piezo1-mediated efferocytosis.

The process of wound healing after an injury is a complex and tightly regulated phenomenon, which can sometimes become arrested, leading to the formation of wounds that fail to heal in a timely manner (chronic wounds, CWs). Today, CWs are a rising global healthcare problem, aggravated by the increase in obesity and diabetes. They affect millions of people worldwide, deeply restricting their quality of life and often leading to amputations or even death. Moreover, pathogenic microorganisms colonize 60-80% of these wounds, further delaying healing and worsening patient outcomes. To monitor this condition, patients are subjected to frequent visual inspections of the wound area, which can disturb healing, and sometimes painful, resource-draining biopsies that take days to yield results. The past decade has been marked by a boom in smart dressings, which aim not only to facilitate healing but also to monitor the wound environment. Likewise, microneedle-based (MN-based) devices have been gaining traction as promising alternatives to conventional laboratory-based analysis. In light of these advancements, the number of publications on MN-integrated biosensors for monitoring infected and CWs increased significantly last year, reflecting the growing interest of the research community in this topic and the urgent societal need for these devices. As such, this article aims to review and critically analyze recent trends in the design and development of MN-based sensing platforms for the wound environment, to gain new insights that could accelerate the introduction of minimally invasive sensing products for CW management into the market.

Duo-nano exosome encapsulating hydrogel boosts wound healing across xenogenic and allogenic models.

Impaired wound healing in chronic wounds presents a significant clinical challenge, increasing susceptibility to infection, prolonging treatment duration, and posing a risk to patient survival. Consequently, the development of effective drug delivery systems capable of sustained local drug release at the wound site is crucial. This study addresses this need by designing a novel composite film for the controlled release of Ciprofloxacin (CIP), an antimicrobial agent. The film comprised Gelatin cross-linked with varying Genipin concentrations, incorporating CIP-loaded chitosan microparticles (CIP-CS MPs) prepared by lyophilization (freeze-drying) and oven drying. FTIR spectroscopy confirmed the successful loading of CIP into CIP-CS MPs. SEM images revealed a consistent spherical morphology of the CIP-CS MPs. ATR-IR spectroscopy verified microparticle incorporation within the film. Subsequently, the dressing's properties were evaluated through in vitro release studies, antibacterial assays, and cell viability assessments. The drug encapsulation was 84.9 ± 1.4%, and CIP-CS MPs embedded in the Gelatin matrix provided a sustained drug-release profile, achieving 87.01% release over a 120-h period. Both CIP-CS MPs and the films demonstrated strong antibacterial activity against Gram-positive and Gram-negative bacteria. Mechanical analysis of Genipin-crosslinked Gelatin films (0.5%, 1%, and 2% w/v Genipin) showed improved flexibility, with the 0.5% formulation exhibiting the highest elongation. Importantly, neither the CIP-CS MPs nor the CIP-CS MPs-incorporated films induced cytotoxicity in L929 fibroblast cells over a 48-h incubation period. The designed system significantly extended the drug-release time and effectively provided controlled, sustained Ciprofloxacin release for managing chronic wound infections.

Biomedical textiles for wound care and healing applications

Duo-nano exosome encapsulating hydrogel boosts wound healing across xenogenic and allogenic models.

Procyanidin capsules attenuate PI3K/AKT-mediated mitochondrial dysfunction and accelerate skin wound healing in diabetic mice.

Biorthogonal click-immobilized probiotic membrane vesicles in a dynamic hydrogel for accelerated and scar-minimized wound healing

Metal organic framework based synergistic improvement of hypoxia for optimizing diabetic wounds healing.

A self-healing, pH/glucose-responsive carboxymethyl chitosan and oxidized bacterial nanocellulose hydrogel for insulin and taurine delivery in diabetic wound healing.

A smart GOX–nitric oxide hydrogel for dynamic regulation in diabetic chronic wound healing

NLRP6 drives cutaneous wound healing during Staphylococcus aureus infection in mice.

Mitochondria-targeted co-assembled nanosystem with multimodal mitochondrial DNA level control to alleviate inflammation and promote chronic wound healing.