Clinical treatment of diabetic refractory ulcers is impeded by chronic inflammation and cell dysfunction associated with wound healing. The significant clinical application of bFGF in wound healing is limited by its instability in vivo. Sulfur has been applied for the treatment of skin diseases in the clinic for antibiosis. We previously found that sulfur incorporation improves the ability of selenium nanoparticles to accelerate wound healing, yet the toxicity of selenium still poses a risk for its clinical application. To obtain materials with high pro-regeneration activity and low toxicity, we explored the mechanism by which selenium-sulfur nanoparticles aid in wound healing via RNA-Seq and designed a nanoparticle called Nano-S@bFGF, which was constructed from sulfur and bFGF. As expected, Nano-S@bFGF not only regenerated zebrafish tail fins and promoted skin wound healing but also promoted skin repair in diabetic mice with a profitable safety profile. Mechanistically, Nano-S@bFGF successfully coactivated the FGFR and Hippo signalling pathways to regulate wound healing. Briefly, the Nano-S@bFGF reported here provides an efficient and feasible method for the synthesis of bioactive nanosulfur and bFGF. In the long term, our results reinvigorated efforts to discover more peculiar unique biofunctions of sulfur and bFGF in a great variety of human diseases.

UNASSIGNED: Diabetes is a growing metabolic disease that is characterized by high blood sugar levels with life-threatening results. Diabetic wounds are a major problem because they do not resolve in few days. Major problems affecting wound healing are infection, age, stress, etc. at the wound site, and other associated disease conditions. Lycopene is a red pigment obtained from various fruits such as tomatoes, watermelon, and guava. It is a powerful antioxidant that scavenges reactive oxygen species and potential as nutraceuticals. It has reported antidiabetic, antioxidant, anti-obesity, anti-inflammatory, antihyperglycemic, and antiaging activities based on the literature.
UNASSIGNED: The objective of the current study is to find the wound-healing potential of lycopene emulgel (LE) and report the properties of the compound.
UNASSIGNED: Wound healing activity was assessed in Streptozotocin induced diabetic rats and control rats. Streptozotocin injection (55 mg/kg) was used to induce marked hyperglycaemia, compared with controls. The formulation was applied topically and was evaluated for efficacy.
UNASSIGNED: Treatment of rats with lycopene emulgel (LE) topical application exhibited a significant reduction of wound closure of 95.3 and 88.9% and epithelisation within 21 days.
UNASSIGNED: The formulation was found to be novel, safe, and effective in the functional recovery of wounds.

UNASSIGNED: This research was to innovate a nanozyme-based therapeutic strategy that combines aggregation-induced emission (AIE) photosensitizers with copper nanozymes. This approach is designed to address the hypoxic conditions often found in bacterial infections and aims to boost the effectiveness of photodynamic therapy (PDT) by ensuring sufficient oxygen supply for reactive oxygen species (ROS) generation.
UNASSIGNED: Our approach involved the synthesis of dihydroxyl triphenyl vinyl pyridine (DHTPY)-Cu@zoledronic acid (ZOL) nanozyme particles. We initially synthesized DHTPY and then combined it with copper nanozymes to form the DHTPY-Cu@ZOL composite. The nanozyme\'s size, morphology, and chemical properties were characterized using various techniques, including dynamic light scattering, transmission electron microscopy, and X-ray photoelectron spectroscopy. We conducted a series of in vitro and in vivo tests to evaluate the photodynamic, antibacterial, and wound-healing properties of the DHTPY-Cu@ZOL nanozymes, including their oxygen-generation capacity, ROS production, and antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA).
UNASSIGNED: The DHTPY-Cu@ZOL exhibited proficient H2O2 scavenging and oxygen generation, crucial for enhancing PDT in oxygen-deprived infection environments. Our in vitro analysis revealed a notable antibacterial effect against MRSA, suggesting the nanozymes\' potential to disrupt bacterial cell membranes. Further, in vivo studies using a diabetic rat model with MRSA-infected wounds showed that DHTPY-Cu@ZOL markedly improved wound healing and reduced bacterial presence, underscoring its efficacy as a non-antibiotic approach for chronic infections.
UNASSIGNED: Our study suggests that DHTPY-Cu@ZOL is a highly promising approach for combating antibiotic-resistant microbial pathogens and biofilms. The biocompatibility and stability of these nanozyme particles, coupled with their improved PDT efficacy position them as a promising candidate for clinical applications.

Healing of chronic diabetic wounds is challenging due to complications of severe inflammatory microenvironment, bacterial infection and poor vascular formation. Herein, a novel injectable polyvinyl alcohol-hyaluronic acid-based composite hydrogel was developed, with tannic acid (TA) and silicate functionalization to fabricate an \'all-in-one\' hydrogel PTKH. On one hand, after being locally injected into the wound site, the hydrogel underwent a gradual sol-gel transition in situ, forming an adhesive and protective dressing for the wound. Manipulations of rheological characteristics, mechanical properties and swelling ability of PTKH could be performed via regulating TA and silicate content in hydrogel. On the other hand, PTKH was capable of eliminating reactive oxygen species overexpression, combating infection and generating a cell-favored microenvironment for wound healing acceleration in vitro. Subsequent animal studies demonstrated that PTKH could greatly stimulate angiogenesis and epithelization, accompanied with inflammation and infection risk reduction. Therefore, in consideration of its impressive in vitro and in vivo outcomes, this \'all-in-one\' multifunctional hydrogel may hold promise for chronic diabetic wound treatment.

Diabetic wounds, characterized by prolonged inflammation and impaired vascularization, are a serious complication of diabetes. This study aimed to design a gelatin methacrylate (GelMA) hydrogel for the sustained release of netrin-1 and evaluate its potential as a scaffold to promote diabetic wound healing. The results showed that netrin-1 was highly expressed during the inflammation and proliferation phases of normal wounds, whereas it synchronously exhibited aberrantly low expression in diabetic wounds. Neutralization of netrin-1 inhibited normal wound healing, and the topical application of netrin-1 accelerated diabetic wound healing. Mechanistic studies demonstrated that netrin-1 regulated macrophage heterogeneity via the A2bR/STAT/PPARγ signaling pathway and promoted the function of endothelial cells, thus accelerating diabetic wound healing. These data suggest that netrin-1 is a potential therapeutic target for diabetic wounds.

Diabetes mellitus (DM), an increasingly prevalent chronic metabolic disease, is characterised by prolonged hyperglycaemia, which leads to long-term health consequences. Although much effort has been put into understanding the pathogenesis of diabetic wounds, the underlying mechanisms remain unclear. The advent of single-cell RNA sequencing (scRNAseq) has revolutionised biological research by enabling the identification of novel cell types, the discovery of cellular markers, the analysis of gene expression patterns and the prediction of developmental trajectories. This powerful tool allows for an in-depth exploration of pathogenesis at the cellular and molecular levels. In this editorial, we focus on progenitor-based repair strategies for diabetic wound healing as revealed by scRNAseq and highlight the biological behaviour of various healing-related cells and the alteration of signalling pathways in the process of diabetic wound healing. ScRNAseq could not only deepen our understanding of the complex biology of diabetic wounds but also identify and validate new targets for intervention, offering hope for improved patient outcomes in the management of this challenging complication of DM.

UNASSIGNED: Wound healing is a complex biological process that can be impaired in individuals with diabetes. Diabetic wounds are a serious complication of diabetes that require promoting diagnosis and effective treatment. FGF-21, a member of the endocrine FGF factors family, has caught the spotlight in the treatment of diabetes for its beneficial effects on accelerating human glucose uptake and fat catabolism. However, the therapeutic efficacy of FGF-21 in promoting diabetic wounds remains unknown. This study aims to evaluate the therapeutic potential of FGF-21 in promoting diabetic wound healing.
UNASSIGNED: we investigated the effects of FGF-21 on wound healing related-cells under high-glucose conditions using various assays such as CCK8, scratch assay, flow cytometry analysis, endothelial tube-formation assay, and transmission electron microscopy. Furthermore, we used db/db mice to verify the healing-promoting therapeutic effects of FGF-21 on diabetic wounds. We also conducted qRT-PCR, Western blot, and immunofluorescence staining analyses to elucidate the underlying mechanism.
UNASSIGNED: Our results indicate that FGF-21 treatment restored hyperglycemic damage on endothelial cell proliferation, migration, and tube-forming ability. It also reduced endothelial cell death rates under high-glucose conditions. TEM analysis showed that FGF-21 treatment effectively restored mitochondrial damage and morphological changes in endothelial cells caused by glucose. Additionally, qRT-PCR and Western blot analysis indicated that FGF-21 treatment restored inflammatory responses caused by hyperglycemic damage. Animal experiments confirmed these findings, suggesting that FGF-21 may be a promising candidate for the treatment of non-healing diabetic wounds due to its effectiveness in stimulating angiogenesis and anti-inflammatory function.
UNASSIGNED: Our study provides evidence that FGF-21 is an essential regulator of wound-related cells under high-glucose conditions and has the potential to be a novel therapeutic target for accelerating diabetic wound healing.

Diabetic wound healing is a significant clinical challenge because abnormal immune cells in the wound cause chronic inflammation and impair tissue regeneration. Therefore, regulating the behavior and function of macrophages may be conducive to improving treatment outcomes in diabetic wounds. Herein, sulfated chitosan (26SCS)-containing composite sponges (26SCS-SilMA/Col-330) with well-arranged layers and high porosity were constructed based on collagen and silk fibroin, aiming to induce an appropriate inflammatory response and promote angiogenesis. The results indicated that the ordered topological structure of composite sponges could trigger the pro-inflammatory response of Mφs in the early stage, and rapid release of 26SCS in the early and middle stages (within the concentration range of 1-3 mg/mL) induced a positive inflammatory response; initiated the pro-inflammatory reaction of Mφs within 3 days; shifted M1 Mφs to the M2 phenotype within 3-7 days; and significantly up-regulated the expression of two typical angiogenic growth factors, namely VEGF and PDGF-BB, on day 7, leading to rapid HUVEC migration and angiogenesis. In vivo data also demonstrated that on the 14th day after surgery, the 26SCS-SilMA/Col-330-implanted areas exhibited less inflammation, faster re-epithelialization, more abundant collagen deposition and a greater number of blood vessels in the skin tissue. The composite sponges with higher 26SCS contents (the (5.0) 26SCS-SilMA/Col-330 and the (7.5) 26SCS-SilMA/Col-330) could better orchestrate the phenotype and function of Mφs and facilitate wound healing. These findings highlight that the 26SCS-SilMA/Col-330 sponges developed in this work might have great potential as a novel dressing for the treatment of diabetic wounds.

UNASSIGNED: One of the key obstacles to the healing of diabetic wound is the persistence of active inflammation. We previously demonstrated the potential of cell-free fat extract (CEFFE) to promote the healing of diabetic wounds, and annexin A5 (A5) is a crucial anti-inflammatory protein within CEFFE. This study aimed to evaluate the therapeutic potential of A5 in diabetic wounds.
UNASSIGNED: A5 was loaded into GelMA hydrogels and applied to skin wounds of diabetic mice in vivo. The diabetic wounds with the treatment of GelMA-A5 were observed for 14 days and evaluated by histological analysis. Accessment of inflammation regulation were conducted through anti-CD68 staining, anti-CD86 and anti-CD206 staining, and qRT-PCR of wound tissue. In presence of A5, macrophages stimulated by lipopolysaccharide (LPS) in vitro, and detected through qRT-PCR, flow cytometry, and immunocytofluorescence staining. Besides, epithelial cells were co-cultured with A5 for epithelialization regulation by CCK-8 assay and cell migration assay.
UNASSIGNED: A5 could promote diabetic wound healing and regulate inflammations by promoting the transition of macrophages from M1 to M2 phenotype. In vitro experiments demonstrated that A5 exerted a significant effect on reducing pro-inflammatory factors and inhibiting the polarization of macrophages from M0 toward M1 phenotype. A5 significantly promoted the migration of epithelial cells.
UNASSIGNED: Annexin A5 has a significant impact on the regulation of macrophage inflammation and promotion of epithelialization.

Diabetic wounds are a difficult medical challenge. Excessive secretion of matrix metalloproteinase-9 (MMP-9) in diabetic wounds further degrades the extracellular matrix and growth factors and causes severe vascular damage, which seriously hinders diabetic wound healing. To solve these issues, a double-network porous hydrogel composed of poly (methyl methacrylate-co-acrylamide) (p(MMA-co-AM)) and polyvinyl alcohol (PVA) was constructed by the high internal phase emulsion (HIPE) technique for the delivery of potassium sucrose octasulfate (PSO), a drug that can inhibit MMPs, increase angiogenesis and improve microcirculation. The hydrogel possessed a typical polyHIPE hierarchical microstructure with interconnected porous morphologies, high porosity, high specific surface area, excellent mechanical properties and suitable swelling properties. Meanwhile, the p(MMA-co-AM)/PVA@PSO hydrogel showed high drug-loading performance and effective PSO release. In addition, both in vitro and in vivo studies showed that the p(MMA-co-AM)/PVA@PSO hydrogel had good biocompatibility and significantly accelerated diabetic wound healing by inhibiting excessive MMP-9 in diabetic wounds, increasing growth factor secretion, improving vascularization, increasing collagen deposition and promoting re-epithelialization. Therefore, this study provided a reliable therapeutic strategy for diabetic wound healing, some theoretical basis and new insights for the rational design and preparation of wound hydrogel dressings with high porosity, high drug-loading performance and excellent mechanical properties.