Diabetes mellitus is a debilitating and worrisome chronic disease with many complications such as cardiovascular disease, kidney damage, blindness and diabetic wounds. Despite advances in the treatment of diabetic wounds, there are still concerns regarding the management of diabetic wound healing, particularly the inflammatory phase. In addition to many treatments with successful effects on wound healing in diabetic patients, short-chain fatty acids (SCFA) acetate, propionate, butyrate, valproate and valerate and their by-products have recently been proposed as new treatments for wound healing in diabetic patients. We provide an overview of the most recent studies on the effectiveness of the above-mentioned SCFAs in the treatment of diabetic wounds as well as possible effects on cytokines in this area of ​​study.

Wound healing in chronic diabetic patients remains challenging due to the multiple types of cellular dysfunction and the impairment of multidimensional microenvironments. The physical signals of structural anisotropy offer significant potential for orchestrating multicellular regulation through physical contact and cellular mechanosensing pathways, irrespective of cell type. In this study, we developed a highly oriented anisotropic nanofiber hydrogel designed to provide directional guidance for cellular extension and cytoskeletal organization, thereby achieving pronounced multicellular modulation, including shape-induced polarization of macrophages, morphogenetic maturation of Schwann cells, oriented extracellular matrix (ECM) deposition by fibroblasts, and enhanced vascularization by endothelial cells. Additionally, we incorporated a VEGF-mimicking peptide to further reinforce angiogenesis, a pivotal phase that interlocks with immune regulation, neurogenesis, and tissue regeneration, ultimately contributing to optimized inter-microenvironmental crosstalk. In vivo studies validated that the anisotropic bioactive nanofiber hydrogel effectively accelerated diabetic wound healing by harnessing the triadic synergy of the immune-angiogenic-neurogenic microenvironments. Our findings highlight the promising potential of combining physical and bioactive signals for the modulation of various cell types and the refinement of the multidimensional microenvironment, offering a novel strategy for diabetic wound healing.

Endogenous electric field (EF) originating from differences in ionic gradients plays a decisive role in the wound healing process. Based on this understanding, a self-manipulating sodium ion gradient-based endogenic electrical stimulation dressing (smig-EESD) is developed to achieve passive, non-invasive, endogenic electrical stimulation of wounds, which avoids the side effects of electrode occupancy, electrochemical reactions, and thermal effects present in traditional exogenous electrical stimulation. smig-EESD reduced the potential at the center of the wound by specifically absorbing Na+ in the exudate, ultimately strengthening the wound endogenous EF. Importantly, smig-EESD converted the active transport dependent on Na+/K+-ATPase into passive diffusion by adsorbing extracellular matrix Na+, and the saved ATP consumption promoted tissue repair process. smig-EESD regulated innate and adaptive immune responses by upregulating the secretion of multiple cytokines, thereby suppressing injury-associated inflammatory responses and reducing scar formation. smig-EESD reveals an endogenic electrical stimulation strategy that is independent of electrodes and circuits, and provides new insights into the future development of electronic medicine.

This study developed a gelatin/alginate-based nanocomposite hydrogel (NC gel), incorporating selenium-doped deferoxamine-derived carbon quantum dots (Se.DFO-CQDs). Initially, Se.DFO-CQDs were synthesized and characterized through several tests, and subsequently, NC gels were created using an dual crosslinking method and analyzed through characterization tests such as SEM, EDX, FT-IR, XRD, tensile strength, water uptake, water vapor transmission rate, weight loss, porosity, blood compatibility, microbial penetration, and DPPH. In vivo studies revealed that NC gels containing Se.DFO-CQDs at 50 % and 0 % exhibited higher wound closure percentages than the control group. The highest wound closure percentage was observed in NC gels with Se.DFO-CQDs at 50 %, reaching 85.7 ± 3.98 % on the 7th day and 98.1 ± 3.95 % on the 14th day. Histological examinations demonstrated that NC gels with Se.DFO-CQDs at 50 % promoted more significant neovascularization, re-epithelialization, and collagen synthesis. Additionally, RT-qPCR results indicated that NC gels with Se.DFO-CQDs at 50 % significantly upregulated the mRNA expression of VEGF-A, bFGF, PDGF-b, and lncRNA GAS5 on the 7th day and COL1A1 on the 14th day. In conclusion, our findings suggest that the NC gels with Se.DFO-CQDs at 50 % show promise for enhancing wound healing and skin regeneration, potentially offering clinical applications.

Gelatin-based biomaterials have emerged as promising candidates for bioadhesives due to their biodegradability and biocompatibility. However, they often face limitations due to the uncontrollable phase transition of gelatin, which is dominated by hydrogen bonds between peptide chains. Here, we developed controllable phase transition gelatin-based (CPTG) bioadhesives by regulating the dynamic balance of hydrogen bonds between the peptide chains using 2-hydroxyethylurea (HU) and punicalagin (PA). These CPTG bioadhesives exhibited significant enhancements in adhesion energy and injectability even at 4 °C compared to traditional gelatin bioadhesives. The developed bioadhesives could achieve self-reinforcing interfacial adhesion upon contact with moist wound tissues. This effect was attributed to HU diffusion, which disrupted the dynamic balance of hydrogen bonds and therefore induced a localized structural densification. This process was further facilitated by the presence of pyrogallol from PA. Furthermore, the CPTG bioadhesive could modulate the immune microenvironment, offering antibacterial, antioxidant, and immune-adjustable properties, thereby accelerating diabetic wound healing, as confirmed in a diabetic wound rat model. This proposed design strategy is not only crucial for developing controllable phase-transition bioadhesives for diverse applications, but also paves the way for broadening the potential applications of gelatin-based biomaterials.

With the aging population, the incidence of diabetes is increasing. Diabetes often leads to restricted neovascularization, antibiotic-resistant bacterial infections, reduced wound perfusion, and elevated reactive oxygen species, resulting in impaired microenvironments and prolonged wound healing. Hydrogels are important tissue engineering materials for wound healing, known for their high water content and good biocompatibility. However, most hydrogels suffer from poor mechanical properties and difficulty in achieving sustained drug release, hindering their clinical application. Inspired by the incorporation of fibers to enhance the mechanical properties of "adobe," core-shell fibers were introduced into the hydrogel. This not only improves the mechanical strength of the hydrogel but also enables the possibility of sustained drug release. In this study, we first prepared core-shell fibers with PLGA (poly(lactic-co-glycolic acid)) and PCL (polycaprolactone). PLGA was loaded with P2 (Parathyroid hormone-related peptides-2), developed by our group, which promotes angiogenesis and cell proliferation. We then designed a QTG (QCS/TA/Gel, quaternary ammonium chitosan/tannic acid/gelatin) hydrogel, incorporating the core-shell fibers and the anti-inflammatory drug celecoxib into the QTG hydrogel. This hydrogel exhibits excellent antibacterial properties and biocompatibility, along with good mechanical performance. This hydrogel demonstrates excellent water absorption and swelling capabilities. In the early stages of wound healing, the hydrogel can absorb the wound exudate, maintaining the stability of the wound microenvironment. This hydrogel promotes neovascularization and collagen deposition, accelerating the healing of diabetic wounds, with a healing rate exceeding 95 % by day 14. Overall, this study provides a promising strategy for developing tissue engineering scaffolds for diabetic wound healing.

The role of inflammation in the development of type 2 diabetes mellitus (T2DM) related skin complications necessitates further investigation. This study aims to explore the correlation between inflammation and cutaneous alterations in T2DM, enhancing comprehension of underlying mechanism involved.

Utilizing bioinformatics, the GSE38396 and GSE92724 datasets were employed to identify differentially expressed genes (DEGs) and potential hub genes in T2DM-related skin inflammation. Subsequently, gene functional enrichment analysis was employed for functional annotation. Finally, we validated the regulatory impact of hub gene on inflammation during high glucose incubation using the in vitro model.

A comprehensive analysis identified 742 DEGs, including 9 hub genes and 4 potential biomarkers. Compared to the CON group, the expression of M2 macrophages was significantly upregulated in the T2DM group, while resting dendritic cells and eosinophils showed notable decreases, indicating a significant correlation with CEBPA. Furthermore, functional enrichment analysis revealed significant enrichment of DEGs in pathways linked to immunity and diabetes pathogenesis. Interestingly, overexpression of CEBPA demonstrated anti-inflammatory effects under hyperglycemic conditions, while silencing CEBPA expression appeared to worsen inflammation.

CEBPA emerges as a potential hub gene for skin inflammation in T2DM, shedding light on the underlying mechanisms of this condition.

The diabetic tissue repair process is frequently hindered by persistent inflammation, infection risks, and a compromised tissue microenvironment, which lead to delayed wound healing and significantly impact the quality of life for diabetic patients. Electromagnetic biomaterials offer a promising solution by enabling the intelligent detection of diabetic wounds through electric and magnetic effects, while simultaneously improving the pathological microenvironment by reducing oxidative stress, modulating immune responses, and exhibiting antibacterial action. Additionally, these materials inherently promote tissue regeneration by regulating cellular behavior and facilitating vascular and neural repair. Compared to traditional biomaterials, electromagnetic biomaterials provide advantages such as noninvasiveness, deep tissue penetration, intelligent responsiveness, and multi-stimuli synergy, demonstrating significant potential to overcome the challenges of diabetic tissue repair. This review comprehensively examines the superiority of electromagnetic biomaterials in diabetic tissue repair, elucidates the underlying biological mechanisms, and discusses specific design strategies and applications tailored to the pathological characteristics of diabetic wounds, with a focus on skin wound healing and bone defect repair. By addressing current limitations and pursuing multi-faceted strategies, electromagnetic biomaterials hold significant potential to improve clinical outcomes and enhance the quality of life for diabetic patients.

N6-methyladenosine (m6A) RNA modification impaired autophagy results in delayed diabetic wound healing. In this study, it was found that fat mass and obesity-associated protein (FTO) was significantly downregulated in the epidermis of diabetic patients, STZ-induced mice and db/db mice (type I and II diabetic mice) with prolonged hyperglycemia, as well as in different types of keratinocyte cell lines treated with short-term high glucose medium. The knockout of FTO affected the biological functions of keratinocytes, including enhanced apoptosis, inhibited autophagy, and delayed wound healing, producing consistent results with high-glucose medium treatment. High-throughput analysis revealed that tribbles pseudokinase 3 (TRIB3) served as the downstream target gene of FTO. In addition, both in vitro and in vivo experiments, TRIB3 overexpression partially rescued biological functions caused by FTO-depletion, promoting keratinocyte migration and proliferation via autophagy. Epigenetically, FTO modulated m6A modification in the 3'UTR of TRIB3 mRNA and enhanced TRIB3 stability in a YTHDF2-dependent manner. Collectively, this study identifies FTO as an accelerator of diabetic wound healing and modulates autophagy via regulating TRIB3 in keratinocytes, thereby benefiting the development of a m6A-targeted therapy for refractory diabetic wounds.

Triboelectric nanogenerators (TENGs) have recently demonstrated great application potential for accelerating wound healing in the field of medical research due to their unique electrical stimulation effect. Among the various types of TENGs, solid-liquid TENGs have attracted much attention due to their significant advantages, such as high contact-separation efficiency and a wide range of liquid motion. Therefore, this study innovatively proposed a solid-liquid biphasic TENG electronic dressing constructed from a casein hydrogel enhanced by the metal-organic framework Zeolitic Imidazolate Framework-8 (ZIF-8). This hydrogel dressing comprised sodium caseinate (SC)/multi-walled carbon nanotubes-polydopamine@polydopamine (MWCNT@PDA)/polyacrylamide (PAM)/ZIF-8. It ingeniously integrates multiple functions such as photothermal, photodynamic antibacterial, and electrical stimulation therapies, thereby establishing a new multimodal synergistic treatment paradigm. Notably, the addition of ZIF-8 not only controlled photothermal release of antibacterial agents but also facilitates the development of a distinctive solid-liquid biphasic operational modality in TENG system, achieving a 131 V peak output voltage through significant enhancement of electrical performance parameters. In addition, the TENG-based system adopts a non-contact electrical stimulation method for wound treatment, fundamentally reducing the risk of infection caused by direct contact. Experiments using mouse fibroblasts revealed that the simultaneous real-time use of near-infrared light and TENG can significantly improve the cell migration process. Empirical studies on animals demonstrated that it could accelerate tissue regeneration and wound healing by increasing collagen deposition and angiogenesis. Based on these results, this study provides new perspectives for the developing intelligent biomedical composites for future wound management. STATEMENT OF SIGNIFICANCE: Chronic wounds have become a major threat to global medical and health fields due to pathogenic infections. Traditional wound dressings mostly focus on passive healing, which has limited effectiveness. To overcome these limitations, we developed an electronic dressing of a casein-based hydrogel TENG enhanced by a MOF. This electronic dressing combines photothermal, photodynamic antibacterial, and electrical stimulation functions and efficiently promotes wound healing through multifunctional synergy. This research provides a promising solution for diabetic wound care and a broader field of chronic wound treatment. It is a solid step in the scientific exploration of interdisciplinary integration, offering new ideas for making the wound treatment field more intelligent, efficient, and precise.

To estimate the cost effectiveness of Topical Wound Oxygen therapy (TWO2) for chronic diabetic foot ulcers.

A Markov model was created to estimate the cost effectiveness of TWO2 over 2 years. Clinical outcome probabilities were estimated from a recent multi-national randomised controlled trial. Diabetic footcare costs were estimated for the National Health Service in England, based on national cost collections, published literature and expert opinion. Model inputs were varied in sensitivity analyses.

Base case results indicate that at a weekly TWO2 price of £650 for up to 12 weeks, total diabetic footcare costs over 2 years are £5038 lower for a patient treated with TWO2 than for standard care, and QALYs are 0.07 higher. Probabilistic sensitivity analysis estimates an 81 % likelihood that the treatment is cost effective at a willingness to pay threshold of £25,000 per QALY.

Base case results indicate that if the clinical outcomes in the RCT are replicated in routine care, TWO2 is a dominant treatment, with lower cost and improved outcomes relative to standard care. Sensitivity analysis shows a high probability that the treatment is cost effective at a willingness to pay threshold of £25,000 per QALY.

Physically crosslinked gelatin microgels were functionalized with a bioadhesive molecule, catechol, to study the effect of in situ generated H2O2 on full-thickness wound repair in diabetic mice. Due to the physically crosslinked nature of the microgels, they transition into a hydrogel film upon hydration. The formation of a hydrogel film was confirmed by the changes in their morphology and viscoelastic properties. Additionally, these microgels released up to 86 μM of H2O2 as a result of catechol autoxidation. The generated H2O2 completely eradicated Staphylococcus epidermidis with an initial concentration of 103 CFU mL-1. These microgels were not cytotoxic and promoted VEGF upregulation in immortalized human keratinocytes (HaCaT) in vitro. When the microgels were applied to a full-thickness dermal wound in diabetic mice, dermal wound closure was accelerated over 14 days, achieving a wound closure of 90% based on the wound area. Microgel-treated wounds also resulted in complete re-epithelialization and regeneration of new dermal tissues with morphology and structure resembling those of native tissues. These results indicate that the release of micromolar concentrations of H2O2 can accelerate wound healing in a healing-impaired animal.

MXene-based materials have attracted significant interest due to their distinct physical and chemical properties, which are relevant to fields such as energy storage, environmental science, and biomedicine. MXene has shown potential in the area of tissue regenerative medicine. However, research on its applications in tissue regeneration is still in its early stages, with a notable absence of comprehensive reviews. This review begins with a detailed description of the intrinsic properties of MXene, followed by a discussion of the various nanostructures that MXene can form, spanning from 0 to 3 dimensions. The focus then shifts to the applications of MXene-based biomaterials in tissue engineering, particularly in immunomodulation, wound healing, bone regeneration, and nerve regeneration. MXene's physicochemical properties, including conductivity, photothermal characteristics, and antibacterial properties, facilitate interactions with different cell types, influencing biological processes. These interactions highlight its potential in modulating cellular functions essential for tissue regeneration. Although the research on MXene in tissue regeneration is still developing, its versatile structural and physicochemical attributes suggest its potential role in advancing regenerative medicine.

Bacterial cellulose (BC) is a natural fiber membrane and has been applied in many biomedical applications. Herein, it was used as the main scaffold to prepare wound dressings for treating diabetic skin wounds. Polypyrrole (PPy) was first synthesized by in situ oxidative polymerization within BC membrane and applied as a photothermal agent, followed by coating with chitosan (CS) to improve the biocompatibility and antibacterial properties. SEM pictures revealed sub-micron PPy particles ranging from 100 to 200 nm were formed and attached to the BC fibrils, whereas CS formed a thin, porous layer on the surface. FTIR analysis showed that there was hydrogen bonding between BC, PPy and CS components. The crystalline structure of BC was maintained yet with decreased crystallinity by addition of PPy and CS. The water absorption capability and water vapor transmission rate decreased by PPy incorporation owing to its hydrophobic nature, but they were regained by addition of hydrophilic CS. The prepared BC/PPy/CS membrane was biocompatible toward L929 cells and maintained hemocompatibility. Additionally, both PPy and CS contributed to the antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, while they demonstrated a potential for synergistic antibacterial effects when combined. Finally, the near-infrared (NIR)-driven photothermal-hyperthermic effects by PPy on lesions upregulated heat-shock protein (HSP) expression and anti-inflammatory properties by CS boosted restoration of diabetic wounds in vivo without the addition of any antibiotics or anti-inflammatory drugs. The results thus support using the BC/PPy/CS membrane for diabetic wound regeneration.

Patients and healthcare systems face significant social and financial challenges due to the increasing number of individuals with chronic external and internal wounds that fail to heal. The complexity of the healing process remains a serious health concern, despite the effectiveness of conventional wound dressings in promoting healing. Recent advancements in materials science and fabrication techniques have led to the development of innovative dressings that enhance wound healing. To further expedite the healing process, novel approaches such as nanoparticles, 3D-printed wound dressings, and biomolecule-infused dressings have emerged, along with cell-based methods. Additionally, gene therapy technologies are being harnessed to generate stem cell derivatives that are more functional, selective, and responsive than their natural counterparts. This review highlights the significant potential of biomaterials, nanoparticles, 3D bioprinting, and gene- and cell-based therapies in wound healing. However, it also underscores the necessity for further research to address the existing challenges and integrate these strategies into standard clinical practice.

Circular RNAs (circRNAs), constituting a novel class of endogenous non-coding RNAs generated through the reverse splicing of mRNA precursors, possess the capacity to regulate gene transcription and translation. Recently, the pivotal role of circRNAs in controlling vascular aging, as well as the pathogenesis and progression of aging-related vascular diseases, has garnered substantial attention. Vascular aging plays a crucial role in the increased morbidity and mortality of the elderly. Endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are crucial components of the intima and media layers of the vascular wall, respectively, and are closely involved in the mechanisms underlying vascular aging and aging-related vascular diseases. The review aims to provide a comprehensive exploration of the connection between circRNAs and vascular aging, as well as aging-related vascular diseases. Besides, circRNAs, as potential diagnostic markers or therapeutic targets for vascular aging and aging-related vascular diseases, will be discussed thoroughly, along with the challenges and limitations of their clinical application. Investigating the role and molecular mechanisms of circRNAs in vascular aging and aging-related vascular diseases will provide a novel insight into early diagnosis and therapy, and even effective prognosis assessment of these conditions.

One of the complication of diabetes mellitus is chronic wounds. The healing of wounds in diabetic patients is retarded by the elevation in the pro-inflammatory cytokines secretion and free radicles accumulation. Wound management in diabetic patients requires preventing bacterial biofilm development. Due to the wound healing activity of chitosan (CS), lecithin (Le) and melatonin (M), the present study aimed to load melatonin on CS/Le NPs and examine their effect on diabetic wounds infected with Staphylococcus aureus. Melatonin loaded chitosan/lecithin nanoparticles (M-CS/Le NPs) were physically characterized and their antioxidant, anti-inflammatory and antimicrobial activities were examined in vitro. Male Sprague Dawley rats included two division (non-diabetic and diabetic) which were further divided in nine groups. Diabetes induction and follow up throughout the experimental period was confirmed by measuring the levels of fructosamine and blood glucose. Full-thickness wounds was induced in both non-diabetic and diabetic animals followed by infection with Staphylococcus aureus according to the experimental design. The wound healing effect of M-CS/Le NPs was evaluated through measurements of the oxidative stress, inflammatory cytokines and apoptotic proteins. Our results showed the anti-microbial, free radical scavenging and hemolysis inhibition effects of M-CS/Le NPs in vitro. Moreover, the preparation of M-CS/Le NPs decreased the dose of used melatonin (when compared to free melatonin). M-CS/Le NPs significantly decreased the wound area percent in treated infected wounds of both non-diabetic and diabetic rats more than free melatonin or unloaded CS/Le NPs. In conclusion, M-CS/Le NPs promoted the wound healing in Staphylococcus aureus-infected wounds in diabetic rats.

Peripheral arterial disease (PAD) is a common complication associated with diabetes, which can lead to foot ischemia. The condition is often accompanied by infection and necrosis, ultimately leading to diabetic foot ulcers and the risk of amputation. Brown adipose tissue (BAT) and its secreted cytokines play an essential role in the regulation of glucose homeostasis, the modulation of inflammatory responses, and vascular endothelial cell proliferation. The transplantation of BAT into ischemic regions may offer therapeutic benefits in alleviating the symptoms associated with PAD. A diabetic mouse model was established via intraperitoneal administration of streptozocin. Subsequently, a diabetic lower limb ulcer model was constructed by transection of the femoral artery and ligation of the femoral vein. BAT harvested from the subscapular region of the mouse was employed as an adipose graft. The research utilized Laser Doppler monitoring, Western blot analysis, hematoxylin-eosin (HE) staining, immunofluorescence staining, and enzyme-linked immunosorbent assay (ELISA) to evaluate blood flow recovery in ischemic regions, histopathological changes, angiogenesis and tissue remodeling, inflammatory responses, and M1/M2 macrophage polarization. BAT transplantation significantly enhanced blood flow recovery in ischemic regions of diabetic lower limb ulcer mice while concurrently reducing necrotic tissue. Pathological analyses demonstrate that BAT transplantation mitigates ischemic tissue damage, stimulates angiogenesis, and supports tissue remodeling. Furthermore, the Western blotting, immunofluorescence, and ELISA results revealed that BAT transplantation significantly reduces inflammatory levels in ischemic tissues, increases the expression of angiogenic factors, and promotes the polarization of macrophages from the M1 to the M2 phenotype. The research has demonstrated that BAT transplantation can mitigate ischemic injury in diabetic lower limb ulcer mice, attenuate inflammatory responses, and facilitate the restoration of blood flow. These effects may be linked to alterations in macrophage polarization.

Diabetic foot ulcer is a common and serious complication of diabetes, with a high risk of amputation, recurrence, and mortality. Aiming at the characteristics of diabetic wounds and based on the result of network pharmacology, a tailored ligand cyanidin-3-O-glucoside (C3G) was selected to construct a metal-phenolic network (CM) through the self-assembly reaction with manganese ions. CM integrates the pharmacological advantages of C3G in antidiabetes and the anti-inflammatory activity of metal-phenolic networks by simulating the metal coordination structure of antioxidant enzymes. Reasonably, the wound areas of db/db mice with CM treatment rapidly decreased to 3.06% at day 14, accompanied by the improvement of tissue microenvironment. Mechanism investigation indicated that CM can not only reduce inflammation activation and immunoreaction but also increase gene transcripts in glucose metabolism, response to hypoxia, and angiogenesis. It is believed that this work opens a way for designing disease-specific metal-phenolic networks, and the CM with high biosafety promotes the clinical treatment of diabetic wounds.

Diabetic wound is one of the most challenge in healthcare, requiring innovative approaches to promote efficient healing. In recent years, lipid nanoparticle-based drug delivery systems have emerged as a promising strategy for enhancing diabetic wound repair by stimulating angiogenesis. These nanoparticles offer unique advantages, including improved drug stability, targeted delivery, and controlled release, making them promising in enhancing the formation of new blood vessels. In this review, we summarize the emerging advances in the utilization of lipid nanoparticles to deliver angiogenic agents and promote angiogenesis in diabetic wounds. Furthermore, we provide an in-depth exploration of key aspects, including the intricate design and fabrication of lipid nanoparticles, their underlying mechanisms of action, and a comprehensive overview of preclinical studies. Moreover, we address crucial considerations pertaining to safety and the translation of these innovative systems into clinical practice. By synthesizing and analyzing the available knowledge, our review offers valuable insights into the future prospects and challenges associated with utilizing the potential of lipid nanoparticle-based drug delivery systems for promoting robust angiogenesis in the intricate process of diabetic wound healing.

Wound infections are characterized by the invasion of microorganisms into bodily tissues, leading to inflammation and potentially affecting any type of wound, including surgical incisions and chronic ulcers. If left untreated, they can delay recovery and cause tissue damage. Healthcare providers face challenges in treating these infections, which necessitate efficient treatment plans involving microbiological testing and clinical evaluation. The effectiveness of conventional treatments like antibiotics is limited by resistance. Various forms of nanotechnology have been developed, each exhibiting unique properties that address particular issues with conventional therapies. Among all the Nanocarriers, zinc oxide nanoparticles (ZnO NPs), offer promising treatments for persistent wound infections. ZnO NPs possess strong antibacterial, antioxidant, anti-inflammatory, and anti-diabetic properties, making them suitable for wound care applications. These nanoparticles can be produced economically and environmentally using green synthesis techniques that minimize toxicity and are biocompatible. While chemical and physical techniques offer precise control over nanoparticle characteristics, they often involve hazardous substances and energy-intensive procedures. The antibacterial qualities, low toxicity, and biological compatibility of green-synthesized ZnO NPs make them a promising treatment for wound infections. Their use in scaffolds, drug delivery systems, and wound dressings provides a viable approach to combat antibiotic resistance and enhance wound treatment outcomes. Furthermore research is necessary to fully realize the benefits of ZnO NPs in clinical practice.

Reactive oxygen species (ROS) play a dual role in wound healing. They act as crucial signaling molecules and antimicrobial agents when present at moderate levels. However, excessive levels of ROS can hinder the healing process for individuals with diabetes. As a result, targeting ROS levels to maintain redox balance has become a promising strategy for improving wound recovery. Currently, no biomaterials have been reported to simultaneously up-regulate and down-regulate ROS to achieve broad-spectrum antibacterial and antioxidant properties. Inspired by the site-dependent effect of nanomaterials, a micron-sized ferroferric oxide (Fe3O4)/MXene (FM) heterojunction is synthesized using a hydrothermal method. The FM heterojunction could scavenge extracellular ROS by activating catalase (CAT)-like and superoxide dismutase (SOD)-like nanozyme activities. Meanwhile, FM heterojunction could release ferric ions and ferrous ions by defect engineering to induce bacterial ferroptosis, up-regulating intercellular ROS, and lipid peroxidation. For applications in vivo, FM heterojunction is incorporated into the tips of gelatin methacryloyl (GelMA)-based microneedle (termed as GFM microneedle) using a two-step casting technique. The results showed that GFM microneedle combined with photothermal therapy could improve S. aureus-infected skin regeneration in diabetic rats. The effectiveness and safety of GFM microneedle are not less favorable than that of a commercial wound dressing. This study provides a proof-of-concept for heterojunction-mediated regenerative medicine via a site-dependent ROS-targeting strategy.

Diabetic foot ulcers (DFUs) are a devastating complication of diabetes, presenting limited treatment success rates due to their complex pathophysiology. Bone morphogenetic protein 7 (BMP7) confers tissue protective and regenerative functions, but its potential role in diabetic wound healing is unknown. The aim of this study was to investigate the effects of topical BMP7 treatment in wound healing using a streptozotocin-induced diabetic mouse model. The expression of markers of wound healing progression were detected using RT-PCR or immunohistochemistry. Overall, BMP7 improved wound closure, as well as maturation of granulation tissue and collagen deposition, as evidenced by hematoxylin and eosin and Masson's trichrome histological analysis. The expression of inflammatory markers (IL-6, TNF-α) and matrix metalloproteinase-9 were decreased in BMP7-treated wounds, together with the number of pro-inflammatory M1 macrophages and T lymphocytes. The number of anti-inflammatory M2 macrophages was increased in BMP7-treated wounds. Moreover, BMP7 decreased oxidative stress and increased Ki67+ cells and CD31+ cells, indicating induced proliferation and angiogenesis in the wound bed compared to the control wounds. Finally, BMP7 activated the ERK pathway and suppressed the p38 pathway in diabetic wounds. Together, our data suggest that BMP7 enhanced skin wound healing in diabetes by decreasing local inflammation and oxidative stress, which promoted a regenerative environment for collagen deposition, wound maturation, cell proliferation, and angiogenesis. These findings underline BMP7 as a potential therapeutic agent for the treatment of skin wounds in diabetes.

Chronic diabetic wounds pose a significant clinical challenge due to the limited efficacy of current treatments. This study aimed to investigate the role and potential mechanisms of adipose-derived mesenchymal stem cells (ADSCs) overexpressing acidic fibroblast growth factor (aFGF) in diabetic wound healing in a rat model.

ADSCs were genetically modified to achieve stable overexpression of aFGF. Varying doses of aFGF-ADSCs (1 × 106, 2 × 106, 3 × 106, 4 × 106) were injected into the muscular tissue surrounding diabetic rat wounds. We assessed aFGF expression and its impact on various stages of wound healing, including angiogenesis, inflammatory response, epithelialization, and collagen deposition. Transcriptomic sequencing was performed to explore the underlying mechanisms driving enhanced wound healing.

Lentiviral transduction successfully induced stable aFGF overexpression in ADSCs. In vivo experiments revealed that varying doses of aFGF-ADSCs markedly enhanced wound healing in diabetic rats in a dose-dependent manner. The dose of 3 × 10⁶ aFGF-ADSCs demonstrated the most significant effect. In the 3 × 106 aFGF-ADSCs group, expression levels of aFGF, CD31, and CD163 were significantly higher than in other groups (p < 0.05), while CD86 expression was significantly lower (p < 0.05).

Single doses of aFGF-ADSCs comprehensively improved various aspects of wound repair in diabetic rats, offering a potential new approach for treating chronic diabetic wounds. The mechanism of action involves promoting angiogenesis, modulating inflammatory responses, accelerating epithelialization, and optimizing collagen deposition.

Deleterious molecules or factors produced by pathogens can hinder the normal physiological functioning of organisms. In response to these survival challenges, organisms rely on innate immune signaling as their first line of defense, which regulates immune-responsive genes and antimicrobial peptides to protect against pathogenic infections. These genes are under the control of transcription factors, which are known to regulate the transcriptional activity of genes after binding to their regulatory sequences. Previous studies have employed Caenorhabditis elegans as a host-pathogen interaction model to demonstrate the essential role of different transcription factors in the innate immunity of worms. In this review, we summarize the advances made regarding the functioning of distinct transcription factors in the innate immune response upon pathogen infection. Finally, we discuss the open questions in the field, whose resolutions have the potential to expand our understanding of the mechanisms underlying the innate immunity of organisms.

Poor wound healing is a refractory process that places an enormous medical and financial burden on diabetic patients. Exosomes have recently been recognized as crucial players in the healing of diabetic lesions. They have excellent stability, homing effects, biocompatibility, and reduced immunogenicity as novel cell-free therapies. In addition to transporting cargos to target cells to enhance intercellular communication, exosomes are beneficial in nearly every phase of diabetic wound healing. They participate in modulating the inflammatory response, accelerating proliferation and reepithelization, increasing angiogenesis, and regulating extracellular matrix remodeling. Accumulating evidence indicates that hydrogels or dressings in conjunction with exosomes can prolong the duration of exosome residency in diabetic wounds. This review provides an overview of the mechanisms, delivery, clinical application, engineering, and existing challenges of the use of exosomes in diabetic wound repair. We also propose future directions for biomaterials incorporating exosomes: 2D or 3D scaffolds, biomaterials loaded with wound healing-promoting gases, intelligent biomaterials, and the prospect of systematic application of exosomes. These findings may might shed light on future treatments and enlighten some studies to improve quality of life among diabetes patients.

Diabetic Foot Ulcers (DFUs) are chronic foot wounds, in a person with diabetes, which are associated with peripheral arterial insufficiency and/or peripheral neuropathy of the lower limb. Recent UK audit figures report that approximately 50-60 % of DFUs remain unhealed after 12 weeks. Previous research has suggested that ischaemia plays a key role in the pathophysiology of many chronic wounds, including DFUs. For this reason, hyperbaric oxygen therapy (HOT) has been investigated. The study aimed to investigate 1) Current understanding of the physiology of normal wound healing and the pathological mechanisms that occur in DFUs to interrupt these processes; 2) Effectiveness of current DFU treatment approaches; 3) Effectiveness from clinical trials and meta-analyses for any demonstrated therapeutic benefits of HOT in the treatment of DFUs, 4) Patient selection criteria for HOT, and patients who stand to benefit most from treatment. The review found that wound healing is a complex process, involving many cells and signalling molecules, and it remains incompletely understood. However, current evidence suggests that hyperglycaemia, hypoxia, chronic inflammation (due to infection, immune-cell dysfunction or other causes), peripheral neuropathy, and macro- and micro-vascular dysfunction may all adversely affect DFU healing. The review found that current NICE guidelines do not approve HOT therapy in the UK for DFU's, despite encouraging clinical research findings. HOT shows theoretical promise and has been successfully used in the treatment of individual DFUs for several decades. Despite this, there remains a lack of strong clinical evidence of benefits to encourage HOT's wider use. The review found that there were four important patient selection criteria for HOT treatment, including glycaemic control, possible contraindications and complications associated with treatment, ulcer severity and resistance to first and second line treatments. The review concluded that further high-quality clinical research is needed to improve the evidence base.

The inability to heal on time is a key component of chronic wounds, which can result in economic, psychological, and physiological burdens. Hydrogels based on amyloid can imitate the extracellular matrix and function as scaffolds for healing wounds. In this direction, a wound dressing inspired by peptide-based amyloid hydrogel is fabricated here. The results demonstrate that the amyloid hydrogel improves the three essential components of skin tissue regeneration: cell migration, proliferation, and collagen remodeling, both in vitro and in vivo. Furthermore, the amyloid hydrogel accelerates wound healing and promotes wound closure within 9 and 15 d in normal and diabetic rats, respectively. Microscopic evaluation of the wound region demonstrates the ultimate stages of regeneration and skin reformation toward normal skin compared to the untreated wound. Hematoxylin and eosin-stained hydrogel-treated wound sites reveal faster dermal bridging, angiogenesis, and epidermal repair in both acute and chronic conditions. The hydrogel creates an environment that encourages the growth of dermal fibroblasts and the release of cytokines, decreasing inflammation with concomitant enhancement of collagen production at the site of injury. Thus, these findings suggest that amyloid-based hydrogel can be a promising candidate for application in acute and chronic wound healing.

Scar formation is a common end-point of the wound healing process, but its mechanisms, particularly in relation to abnormal scars such as hypertrophic scars and keloids, remain not fully understood. This study unveils a novel mechanistic insight into scar formation by examining the differential expression of Homeobox (HOX) genes in response to mechanical forces in fibroblasts derived from normal skin, hypertrophic scars, and keloids.

We isolated fibroblasts from different scar types and conducted RNA sequencing (RNA-Seq) to identify differential gene expression patterns among the fibroblasts. Computational modeling provided insight into tension alterations following injury, and these findings were complemented by in vitro experiments where fibroblasts were subjected to exogenous tensile stress to investigate the link between mechanical tension and cellular behavior.

Our study revealed differential HOX gene expression among fibroblasts derived from normal skin, hypertrophic scars, and keloids. Computational simulations predicted injury-induced tension reduction in the skin, and in vitro experiments revealed a negative correlation between tension and fibroblast proliferation. Importantly, we discovered that applying mechanical tension to fibroblasts can modulate HOX gene expression, suggesting a pivotal role of mechanical cues in scar formation and wound healing.

This study proposes a model wherein successful wound healing and scar formation are critically dependent on maintaining tensional homeostasis in the skin, mediated by tension-sensitive HOX genes. Our findings highlight the potential of targeting mechanotransduction pathways and tension-sensitive HOX gene expression as therapeutic strategies for abnormal scar prevention and treatment, offering a new perspective on the complex process of scar formation.

Recent studies demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RA) have promising prospects in promoting wound healing. In this study, we intend to investigate the pro-healing effect and potential molecular mechanism of topical administration of GLP-1RA liraglutide on wounds in normoglycemic mice. Two full-thickness wounds were created on the back of the C57BL/6 mice. The "lower" wounds were topically infiltrated with liraglutide every day after injury; while the "upper" wounds were infiltrated with saline solution. Wound area was measured daily during the 10-day study period. The wound tissue was stained with H&E and immunofluorescence. Western blotting was performed to detect the markers in macrophages. The results showed that topical administration of liraglutide resulted in a rapid reduction of wound size. The capillary density and the expression of vascular endothelial growth factor (VEGF)-A were significantly increased in liraglutide-treated wounds. Findings from immunofluorescence and Western blotting revealed that liraglutide promoted phenotypic polarization of macrophages from M1 to M2. We further identified that M2a macrophages predominantly presented in the early and middle stages of inflammation phase and M2d macrophages presented in the middle and late stages. Our study suggested that GLP-1RA liraglutide could promote wound healing in normoglycemic mice, which is partly attributed to the modulation of the macrophage polarization from M1 subtype to M2 subtype.

Diabetic wound healing presents significant challenges due to impaired angiogenesis, chronic inflammation, and cellular dysfunction. Building on previous research, this study further explores the potential of a plant-derived glucosyloxybenzyl 2-isobutylmalates (B-CGT) hydrogel in promoting diabetic wound healing. Network pharmacology and molecular docking analyses suggest that B-CGT may regulate key mechanisms, such as apoptosis, inflammation, and matrix remodeling, through core targets including SIRT1, CASP8, and MMP8. In vivo studies further demonstrated that B-CGT hydrogel significantly accelerated wound closure in diabetic mice, enhanced angiogenesis, promoted collagen deposition, and achieved immune balance by modulating macrophage polarization, thereby shifting the inflammatory environment toward a repair state. Moreover, B-CGT hydrogel significantly improved the wound microenvironment by upregulating VEGF expression and exerting antioxidant effects. By combining theoretical predictions with experimental validation, this study elucidates the multi-target synergistic regulatory mechanisms of B-CGT hydrogel. These findings provide new research directions for addressing immune imbalance and angiogenesis defects in diabetic wound healing and lay a scientific foundation for the optimization and application of chronic wound treatment strategies.

The present investigation was undertaken to determine the healing efficacy of Hippophae rhamnoides L. (sea buckthorn (SBT)) leaf aqueous lyophilised extract (SBTL-ALE) on a diabetic wound model in rats. The effect of SBTL-ALE was also evaluated on human epithelial cell lines (A431) by using in vitro wound closure and transwell migration assays.

A total of four full-thickness excision-type wounds were created on the dorsal surface of streptozocin-induced diabetic rats. The animals were divided into two groups: control rats treated with soft white petroleum jelly and experimental rats treated with SBTL-ALE (5.0%, weight/weight) ointment applied topically, twice daily for seven days.

SBTL-ALE significantly (p<0.05) accelerated the migration of epithelial cells in in vitro wound closure and transwell migration assays. Further, SBTL-ALE augmented the healing process by significantly (p<0.05) enhanced wound area contraction, faster complete epithelial closure, increased hydroxyproline (collagen) and hexosamine levels in diabetic rats. Histopathological findings confirmed the healing potential of SBTL-ALE. Immunohistochemical analyses showed increased expression of transforming growth factor (TGF)-β and α-smooth muscle actin in SBTL-ALE-treated wounds of diabetic rats. Superoxide dismutase, catalase and reduced glutathione levels increased, whereas reactive oxygen levels were decreased significantly (p<0.05) in SBTL-ALE-treated wounds compared to diabetic controls, which conferred redox homeostasis.

Our results suggest that SBTL-ALE accelerated transdermal wound healing in diabetic rats by increasing the rate of wound contraction, enhancing levels of collagen, hexosamine and endogenous antioxidants, and reducing oxidative stress.

Wound healing is a dynamic, multi-stage process essential for restoring skin integrity. Dysregulated wound healing is often linked to impaired macrophage function, particularly in individuals with chronic underlying conditions. Macrophages, as key regulators of wound healing, exhibit significant phenotypic diversity, ranging from the pro-healing M2 phenotype to the pro-inflammatory M1 phenotype. Imbalances in the M1/M2 ratio or hyperactivation of the M1 phenotype can delay the normal healing. Consequently, strategies aimed at suppressing the M1 phenotype or promoting the shift of local skin macrophages toward the M2 phenotype can potentially treat chronic non-healing wounds. This manuscript provides an overview of macrophages' role in normal and pathological wound-healing processes. It examines various therapeutic approaches targeting M2 macrophages, such as ex vivo-activated macrophage therapy, immunopharmacological strategies, and biomaterial-directed macrophage polarization. However, it also highlights that M2 macrophage therapies and immunopharmacological interventions may have drawbacks, including rapid phenotypic changes, adverse effects on other skin cells, biotoxicity, and concerns related to biocompatibility, stability, and drug degradation. Therefore, there is a need for more targeted macrophage-based therapies that ensure optimal biosafety, allowing for effective reprogramming of dysregulated macrophages and improved therapeutic outcomes. Recent advances in nano-biomaterials have demonstrated promising regenerative potential compared to traditional treatments. This review discusses the progress of biomaterial-assisted macrophage targeting in chronic wound repair and addresses the challenges faced in its clinical application. Additionally, it explores novel design concepts for combinational therapies, such as incorporating regenerative particles like exosomes into dressing materials or encapsulating them in microneedling systems to enhance wound healing rates.

Keratinocyte and fibroblast dysfunctions contribute to delayed healing of diabetic wounds. Small extracellular vesicles (sEV) are key mediators of intercellular communication and are involved in the pathogenesis of several diseases. Recent findings suggest that sEV derived from high-glucose-treated keratinocyte (HaCaT-HG-sEV) can transport LINC01435 to inhibit tube formation and migration of HUVECs, thereby delaying wound healing. This study aimed to elucidate sEV-related communication mechanisms between keratinocytes and fibroblasts during diabetic wound healing. HaCaT-HG-sEV treatment and LINC01435 overexpression significantly decreased fibroblast collagen level and migration ability but significantly increased fibroblast autophagy. However, treatment with an autophagy inhibitor suppressed LINC01435 overexpression-induced decrease in collagen levels in fibroblasts. In diabetic mice, HaCaT-HG-sEV treatment decreased collagen levels and increased the expression of the autophagy-related proteins Beclin-1 and LC3 at the wound site, thereby delaying wound healing. Conclusively, LINC01435 in keratinocyte-derived sEV activates fibroblast autophagy and reduces fibroblast collagen synthesis, leading to impaired diabetic wound healing.

Effective regulation and reconstruction of the microenvironment are critical for the regeneration of chronic wounds. Diabetic wounds, in particular, pose a significant clinical challenge due to increased oxidative stress and dysfunctional healing processes. In this study, a novel therapeutic strategy is developed using 3D copper-magnesium bimetallic antioxidant nano-enzymes (Cu/Mg-MOF) to mitigate reactive oxygen species (ROS) and restore redox balance through electron transfer. To optimize delivery, a thermo-sensitive hydrogel composed of chitosan (CS) and ε-polylysine (PL) is designed, serving as an efficient carrier for the nano-enzymes. This Cu/Mg-MOF@CS/PL hydrogel exhibits excellent physical properties, including injectability, softness, and biocompatibility, making it ideal for application in diabetic wounds. In a diabetic wound model, treatment with Cu/Mg-MOF@CS/PL hydrogel significantly accelerated wound healing, with a closure rate of 90.6% by day 14, compared to just 55.4% in the untreated group. The hydrogel effectively promoted key aspects of wound healing, such as collagen deposition, re-epithelialization, angiogenesis, and immunomodulation. These findings underscore the potential of the Cu/Mg-MOF@CS/PL hydrogel as a promising therapeutic system for enhancing the healing of diabetic wounds.

Tissue engineering presents promising avenues for addressing issues related to tissue defects and regenerative medicine. However, the translational efficacy of tissue engineering in clinical settings remains limited, primarily due to the inadequate survival rates of implanted tissue scaffolds. This is attributed to the grafts' inability to adequately supply oxygen and their dependence on the diffusion of oxygen from surrounding tissues for tissue regeneration. The integration of oxygen-releasing materials in human tissue engineering is anticipated to enhance the hypoxic microenvironment for tissue regeneration. In recent years, a variety of oxygen-producing or oxygen-carrying biomacromolecules, including gelatin, chitosan, and alginate, have been developed, offering innovative strategies for controlled drug release efficacy, regenerative medicine, and biological systems engineering. This review examines applications of these oxygen-releasing biological macromolecules, primarily derived from natural polymeric materials, in diverse facets of human tissue engineering including skin, heart tissue, tumor therapy. We also highlight recent advancements in this field, with an emphasis on current challenges, potential solutions, and future perspectives.

Multifunctional hydrogels hold significant promise for promoting the healing of infected wounds but often fall short in inhibiting antibiotic-resistant pathogens, and their clinical translation is limited by complex preparation processes and high costs. In this study, a multifunctional hydrogel is developed by combining metal-phenolic networks (MPNs) formed by tannic acid (TA) and gallium ions (Ga3⁺) with chitosan (CS) through a simple one-step method. The resulting CS-TA-Ga3⁺ (CTG) hydrogel is cost-effective and exhibits desirable properties, including injectability, self-healing, pH responsiveness, hemostasis, antioxidant, anti-inflammatory, and antibacterial activities. Importantly, the CTG hydrogels are effective against antibiotic-resistant pathogens due to the unique antibacterial mechanism of Ga3⁺. In vivo studies demonstrate that the CTG hydrogel promotes follicle formation and collagen deposition, accelerating the healing of infected wounds by inhibiting blood loss, suppressing bacterial growth, and modulating the inflammatory microenvironment. These findings highlight the CTG hydrogel's potential as an advanced and translational dressing for enhancing the healing of infected wounds.

Diabetic chronic foot ulcers pose a significant therapeutic challenge around the world, resulting in adverse effects and complications in patients. D-mannose is enriched in cirtus peel and exerts beneficial effects among various diseases, especially against inflammation-related disorders.

Here, we examined the potential effect of D-mannose during wound healing process in streptozotocin (STZ)-induced diabetes mice in vivo and by culturing keratinocytes under high glucose condition in vitro. The skin lesion healing was recorded in photos and evaluated by histochemical staining. What's more, the advanced glycation end products (AGEs) concentration in blood and mice skin was quantified. Apoptotic cells were assessed by flow cytometry and Western blotting. Inflammatory cytokines and cellular differential gene expression levels were measured by real-time PCR. The expression of the AMPK/Nrf2/HO-1 signaling-related molecules was determined by Western blotting.

We first found that topical supplementation of D-mannose remarkably improved skin wound healing in diabetes mice. Furthermore, both in vivo and in vitro experiments demonstrated that D-mannose reduced the AGEs generation. Mechanistically, D-mannose inhibited AGEs, then upregulated AMPK/Nrf2/HO-1 signaling in the context of high glucose to maintain keratinocyte normal functions, which positively influenced macrophage and fibroblast to accelerate diabetic wound healing. Noteworthily, these protective effects of D-mannose were abolished by the pretreatment with inhibitors of AGEs or AMPK.

As far as we know, this is the first study exploring the protective role of D-mannose on diabetic wound healing via topical supplementation. We find that D-mannose protects keratinocytes from high glucose stimulation via inhibition of AGEs formation as well as orchestrates inflammatory microenvironment in diabetic wounded skin, suggesting its supplementation as a potential therapy to promote refractory wound healing in diabetic patients.

Diabetic foot ulcers (DFUs) are a significant contributor to disability and mortality in diabetic patients. Macrophage polarization and functional regulation are promising areas of research and show therapeutic potential in the field of DFU healing. However, the complex mechanism, the difficulty in clinical translation, and the large heterogeneity present significant challenges. Hence, this study was to comprehensively analyze the publication status and trends of studies on macrophage polarization and DFU healing.

To examine the relevant literature on macrophage polarization in DFU healing.

A bibliometric analysis was conducted using the Web of Science database. Relevant literature was retrieved from the Web of Science Core Collection database between 2013 to 2023 using literature visualization and analysis software (VOSviewer and CiteSpace) and bibliometric online platforms. The obtained literature was then subjected to visualization and analysis of different countries/regions, institutions, journals, authors, and keywords to reveal the research's major trends and focus.

The number of publications on the role of macrophage polarization in DFU healing increased rapidly from 2013 to 2023, especially in the latter period. Chinese researchers were the most prolific in this field, with 217 publications, while American researchers had been engaged in this field for a longer period. Qian Tan of Nanjing Drum Tower Hospital and Qian Ding of Nanjing University were the first to publish in this field. Shanghai Jiao Tong University was the institution with the most publications (27). The keywords "bone marrow", "adjustment, replacement, response, tissue repair", and "activation, repair, differentiation" appeared more frequently. The study of macrophage polarization in DFU healing focused on the regulatory mechanism, gene expression, and other aspects.

This study through the bibliometric method reveals the research trends and development trends in this field of macrophage polarization in DFU healing from 2013 to 2023 in the Web of Science Core Collection database. The key hotspots in this field mainly include the regulation of macrophage activation, gene expression, wound tissue repair, and new wound materials. This study provides references for future research directions.