Diabetic Wound Healing Research Articles

Pyroligneous extract, a biomaterial derived from pyrolytic palm kernel shell wood vinegar, as a novel diabetic wound healing aid: An animal study.

Objective Wound in diabetes is difficult to heal since it possesses excessive inflammation. The aim of the study was to evaluate wound healing activity of chitosan-based hydrogel containing pyroligneous acid in diabetic animals. Significance Pyroligneous acid, a byproduct of biochar production from palm kernel shell biomass, contained oxygenated compounds which, with extracting enrichment, could promote wound healing. Methods Streptozotocin-induced diabetic male jcl: ICR mice were subjected to create wounds and treat with hydrogel containing pyroligneous extract at dose strengths of 0 (placebo), 100 and 150 μg/g-gel. Commercial gel (Intrasite®) was used as an active comparator. On 3-, 7-, 10- and 14-day post wounding, wound contraction was rated and wound site tissues were collected. The specimens were H&E stained and microscopically examined to evaluate histological responses. The underline wound healing related cytokine and polypeptide expressions were determined using real-time PCR and western blot. Results It was found that the extract accelerated the healing process in a dose-dependent manner where at dose strength of 150 μg/g-gel was as effective as active comparator. It increased gene expression of the cytokine and related proteins in TGF-β/SMAD signaling pathway and may further activate diabetic induced TGF-β downregulation to restore up to the level that healthy skin tissues express. It also enhanced the expressions of Akt, FAK, RhoA and Rac-1 and evidently activated phosphorylation of Akt and FAK. Conclusion The study demonstrated the extract could be a novel biomaterial for healing of such a chronic inflammatory wound as the wound in diabetes.

Conductive polyphenol microneedles coupled with electroacupuncture to accelerate wound healing and alleviate depressive-like behaviors in diabetes

Inflammation and depression are serious complications of diabetes that interact to form a feedback loop and may hinder diabetic wound healing. They share a common pathophysiological basis of abnormal interactions between diabetic wounds and the brain. Here, we propose a strategy combining electroacupuncture (EA) stimulation of the Dazhui acupoint (GV14) with polyphenol-mediated conductive hydrogel microneedles to promote diabetic wound healing and alleviate depression through local wound–brain interactions. The conductive microneedles comprised methacrylated gelatin, dopamine (DA), DA-modified poly(3,4-ethylenedioxythiophene), and Lycium barbarum polysaccharide. EA at GV14 activated the vagus–adrenal axis to inhibit systemic inflammation while DA coupled electrical signals for long-term inhibition of local wound inflammation. EA at GV14 was also found to elevate 5-hydroxytryptamine levels in rats with diabetic wounds, consequently mitigating depressive-like behaviors. Additionally, the polyphenol-mediated conductive hydrogel microneedles, and coupled with EA stimulation promoted healing of wound tissue and peripheral nerves. This strategy regulated both local and systemic inflammation while alleviating depressive-like behaviors in diabetic rats, providing a new clinical perspective for the treatment of diabetes-related and emotional disorders.

Topical Reconstituted High-Density Lipoproteins Elicit Anti-Inflammatory Effects in Diabetic Wounds.

Objective: Reconstituted high-density lipoproteins (rHDL) improve wound healing in diabetes. We aimed to determine if rHDL elicit anti-inflammatory effects in diabetic wounds, as a mechanism to explain their wound healing benefits. Approach: Diabetes was induced using streptozotocin in C57Bl6/J mice. Two full-thickness wounds were placed on the subflanks of diabetic and nondiabetic (ND) mice. Phosphate-buffered saline (PBS) or rHDL (50 µg/wound/day) were applied topically. Wound closure was assessed daily. Inflammatory gene transcripts were measured by qPCR and proteins by Western blotting and enzyme-linked immunosorbent assay in wounds collected at baseline, 24 h, and 3 days postwounding. Wound macrophages were assessed by flow cytometry 7 days postwounding. The fate of fluorescent 3,3-dioctadecyloxacarbocyanine, perchlorate (DiO)-labeled rHDL was tracked by flow cytometry, fluorescent imaging, and microscopy. Results: In diabetic mice, rHDL increased wound closure rates at days 6 (+288%, p < 0.01) and 7 (+639%, p < 0.0001) postwounding, compared with PBS controls. After 3 days, rHDL-treated diabetic wounds had lower Rela (-65%) and C-C motif chemokine ligand 2 (Ccl2) (-59%) mRNA levels and CCL2 protein (29%) than PBS controls, p < 0.05 for all. Wound macrophage content was higher in diabetic than ND wounds, but rHDL did not change macrophage content or polarity. DiO-rHDL were taken up by key wound cells including fibroblasts, macrophages, keratinocytes and endothelial cells, and retained in wounds for at least 48 h. Innovation: rHDL exerts anti-inflammatory effects in diabetic wounds early postwounding, which may contribute to its wound healing properties. Conclusion: The anti-inflammatory properties of rHDL in diabetic wounds present topical rHDL as a novel treatment option for improving healing in patients with diabetic foot ulcers.

Endogenous/exogenous stimuli‐responsive smart hydrogels for diabetic wound healing

AbstractDiabetes significantly impairs the body's wound‐healing capabilities, leading to chronic, infection‐prone wounds. These wounds are characterized by hyperglycemia, inflammation, hypoxia, variable pH levels, increased matrix metalloproteinase activity, oxidative stress, and bacterial colonization. These complex conditions complicate effective wound management, prompting the development of advanced diabetic wound care strategies that exploit specific wound characteristics such as acidic pH, high glucose levels, and oxidative stress to trigger controlled drug release, thereby enhancing the therapeutic effects of the dressings. Among the solutions, hydrogels emerge as promising due to their stimuli‐responsive nature, making them highly effective for managing these wounds. The latest advancements in mono/multi‐stimuli‐responsive smart hydrogels showcase their superiority and potential as healthcare materials, as highlighted by relevant case studies. However, traditional wound dressings fall short of meeting the nuanced needs of these wounds, such as adjustable adhesion, easy removal, real‐time wound status monitoring, and dynamic drug release adjustment according to the wound's specific conditions. Responsive hydrogels represent a significant leap forward as advanced dressings proficient in sensing and responding to the wound environment, offering a more targeted approach to diabetic wound treatment. This review highlights recent advancements in smart hydrogels for wound dressing, monitoring, and drug delivery, emphasizing their role in improving diabetic wound healing. It addresses ongoing challenges and future directions, aiming to guide their clinical adoption.

A Novel Look at Mechanisms and Applications of Xanthohumol (XN) in Dermatology and Cosmetology

Xanthohumol (XN), representing the group of chalcones, is a hydroxyl and superoxide free radical scavenger. It also has antimicrobial properties, showing antibacterial activity against Staphylococcus aureus, Staphylococcus pyogenes, Staphylococcus epidermidis and Propionibacterium acnes. XN exerts an inhibitory effect on tyrosinase (it hinders the oxidation of l-tyrosine and l-DOPA). However, it also affects the transport of pigment (through a reduction in the number and length of dendrites) and its degradation (through damage to melanosomes). Additionally, it has been shown to inhibit the different activation pathways of the premeditated response in macrophages and reduce the secretion of pro-inflammatory cytokines TNF-α, IL-6 and IL-1β. Xanthohumol also improves skin elasticity by reducing the activity of elastase and MMP 1, 2 and 9, and it increases the expression of type I, III and V collagen, as well as elastin and fibrillins in skin fibroblasts. It acts against the main factors contributing to the pathogenesis of acne by inhibiting pro-inflammatory mediators (e.g., COX-2, PGE2, IL-1β and TNF-α). Moreover, it shows antibacterial activity against P. acnes and S. aureus, as well as seboregulatory and antioxidant properties. It has also been recognized that XN intake could affect diabetic wound healing. XN shows antitumoral activity, e.g., in the case of skin melanoma, which is associated with the antioxidant, pro-apoptotic, anti-angiogenic and immunostimulating effects of this compound.

Dental Pulp Stem Cell Lysate-Based Hydrogel Improves Diabetic Wound Healing via the Regulation of Anti-Inflammatory Macrophages and Keratinocytes.

The prolonged existence of chronic wounds heightens the risk of patients experiencing chronic pain, necrosis, and amputation. Dental pulp stem cells (DPSCs) have garnered attention due to their potential immunomodulatory and tissue repair regenerative effects in the management of chronic wounds. However, stem-cell-based therapy faces challenges such as malignant differentiation, immune rejection, and long-term effectiveness. To overcome these challenges, we proposed a chronic wound therapy using a hydrogel derived from human-originated dental pulp stem cell lysate (DPSCL). Our data indicate that, with the degradation of the dental pulp stem cell lysate-based hydrogel (DPSCLH), the slowly released cell lysates recruit anti-inflammatory M2 macrophages and promote the proliferation, migration, and keratinization of HacaT cells. In addition, in vivo studies revealed that DPSCLH avoids immune rejection reactions and induces a long-term accumulation of endogenous M2 macrophages. In a mouse model of diabetic wounds, DPSCLH effectively modulates the inflammatory microenvironment around diabetic wounds, promotes the formation of the stratum corneum, and facilitates the healing of wounds, thus holding tremendous potential for the treatment of diabetic wounds.

Extracellular Vesicles from Human Adipose-Derived Stem Cell Spheroids: Characterization and Therapeutic Implications in Diabetic Wound Healing

The management of diabetic wounds presents a considerable challenge within the realm of clinical practice. Cellular-derived nanoparticles, or extracellular vesicles (EV), generated by human adipose-derived stem cells (hASCs) have been investigated as promising candidates for the treatment of diabetic wounds. Nevertheless, limitations on the yield, as well as the qualitative angiogenic properties of the EV produced, have been a persistent issue. In this study, a novel approach involving the use of various cell culture morphologies, such as cell spheroids, on hASC was used to promote both EV yield and qualitative angiogenic properties for clinical use, with an emphasis on the in vivo angiogenic properties exhibited by the EV. Moreover, an increase in the secretion of the EV was confirmed after cell spheroid culture. Furthermore, microRNA(miRNA) analysis of the produced EVs indicated an increase in the presence of wound healing-associated miRNAs on the cell spheroid EV. Analysis of the effectiveness of the treated EVs in vitro indicated a significant promotion of the biological function of fibroblast and endothelial cells, cell migration, and cell proliferation post-cell spheroid EV application. Meanwhile, in vivo experiments on diabetic rats indicated a significant increase in collagen production, re-epithelization, and angiogenesis of the diabetic wound after EV administration. In this investigation, we posit that the use of cell spheroids for the culture of hASC represents a novel approach to enhance the substantial secretion of extracellular vesicles while increasing the angiogenic wound healing properties. This innovation holds promise for augmenting the therapeutic potential of EVs in diabetic wound healing, aligning with the exigencies of clinical applications for these nanoparticles.

Effect of hyaluronic acid on the formation of acellular dermal matrix-based interpenetrating network sponge scaffolds for accelerating diabetic wound healing through photothermal warm bath

Adequate vascularization essential for delivering nutrients critical to wound healing, yet impaired angiogenesis is a major barrier in diabetic wound repair. This study investigates the impact of hyaluronic acid on interpenetrating network sponge scaffolds derived from an acellular dermal matrix, with the aim of enhancing vascularization and healing of diabetic wounds via photothermal warm bath therapy. We prepared three-dimensional porous sponges (H1P4D2@DFO) using molecular interpenetration and ion crosslinking of porcine acellular dermal matrix (PADM), hyaluronic acid, and polydopamine nanoparticles loaded with deferoxamine mesylate (PDA@DFO). This resulting extracellular matrix-based sponge demonstrated properties suitable for wound repair, including high cell adhesion, biocompatibility, bioactivity, porosity (85 %), and water absorption (4500 %). The near-infrared (NIR) photothermal effect of PDA@DFO and the sustained release of deferoxamine mesylate (DFO) enhanced wound vascularization within the wound site. These findings suggest that our sponge scaffold can simulate skin-like structures and establish a supportive microenvironment conducive to microvascular reconstruction. By combining the photothermal warm bath approach with the scaffold's tailored 3D structure, we observed enhanced angiogenesis and accelerated diabetic wound healing, indicating potential clinical applications of these scaffolds in chronic wound management.

Microneedles based on hyaluronic acid-polyvinyl alcohol with antibacterial, anti-inflammatory, and antioxidant effects promote diabetic wound healing

Diabetic wound healing has become one of the major clinical burdens due to uncontrolled bacterial growth and an increase in the risk of various microbial infections. Despite excellent antioxidant properties, the poor aqueous solubility of resveratrol (RES) hampers its applicability. In this study, we proposed a novel multifunctional microneedle patch loaded with RES-encapsulated polymeric micelles. Resveratrol micelles (RES MC) were loaded in the microneedle tip, while the base part was coated with the antibiotic gentamicin (GEN) to promote wound healing. The microneedle tip composed of sodium hyaluronate (HA) could effectively deliver the anti-inflammatory and antioxidant RES MC. Furthermore, the base of the microneedle patch composed of polyvinyl alcohol (PVA) offered excellent flexibility, releasing GEN and providing resistance to bacterial contamination, thereby further promoting wound repair. In vitro antibacterial experiments indicated that the bactericidal rate reached 99 %. Further, the wound healing rate was recorded as 86.05 % on the 11th day of diabetes wound treatment. Together, the multifunctional microneedle patch with excellent biocompatibility exhibited anti-inflammatory, antioxidant, and antibacterial effects on the wound healing process, potentiating its efficacy in the treatment of diabetic wounds.

Improving diabetic wound healing: The therapeutic potential of allulose supplement in diabetic skin tissue repair and inflammation modulation

The increasing prevalence of type 2 diabetes mellitus (T2DM) worldwide presents significant challenges in the management of impaired tissue repair in diabetic skin wounds, which has emerged as a critical health concern. Addressing this issue while minimizing adverse effects remains crucial. Allulose has been shown to exhibit hypolipidemic and anti-inflammatory properties, alleviating obesity and atherosclerosis by improving insulin resistance and impaired glucose tolerance. However, its underlying effects and mechanisms in repairing diabetic skin damage remain poorly understood. In this study, we demonstrated that oral administration of allulose remarkably ameliorated T2DM-compromised skin tissue wound associated with the stimulation of skin granulation, surrounding tissue formation, and activated fibroblasts, under high-fat diet (HFD) feeding condition. In addition, administration partially promoted collagen deposition, reduced M1 macrophage polarization, facilitated neovascularization, and mitigated tissue inflammation in the T2DM rats upon HFD feeding. Moreover, allulose could significantly alleviate high glucose stress condition-induced inflammatory response, correlative with modulation of p38/NLRP3/Caspase-1 signaling. In addition, allulose could also ameliorate high glucose stress-compromised cell viability and proliferative capacity, related to stimulation of mTOR pathway in part. Taken together, our study revealed that T2DM compromised some certain factors which are crucial for skin tissue healing and wound repair upon HFD condition. The work highlighted the potential beneficial effects of orally administered allulose for healing diabetic skin wounds and supported a novel strategy for managing diabetes patients adjunctively with allulose dietary supplement.

Engineered biomimetic nanovesicles-laden multifunctional hydrogel enhances targeted therapy of diabetic wound

Angiogenesis is essential for diabetic wound healing. Endothelial progenitor cell-derived extracellular vesicles (EPC-EVs) are known to promote wound healing by enhancing angiogenesis, while the low yield and lack of effective targeting strategies limit their therapeutic efficacy. Here, the biomimetic nanovesicles (NVs) prepared from EPC (EPC-NV) through an extrusion approach were reported, which functioned as EV mimetics to deliver contents from EPC to the wound. Besides, the cRGD peptide was coupled to the surface of EPC-NV (mEPC-NV) to achieve active endothelial cells (ECs)-targeting. Furthermore, we developed a dual hydrogel network by combining Fe3+@ Protocatechualdehyde (PA) complex-modified Acellular Dermal Matrix (ADM) with light-cured gelatin (GelMA), to enrich and sustainably release mEPC-NV. The hydrogel system with antioxidant and antibacterial properties also made up for the deficiency of mEPC-NV, reducing reactive oxygen species (ROS) and inhibiting infection in diabetic wound. Taken together, this study established a novel bioactive delivery system with angiogenesis, antioxidant and antibacterial activities, which might be a promising strategy for the treatment of diabetic wound.

Rational design of bioengineered recombinant collagen-like protein enhances GelMA hydrogel for diabetic wound healing

Gelatin methacryloyl (GelMA) holds significant potential in tissue engineering; however, its clinical applications are often constrained by its lack of functional groups. To overcome this limitation, recombinant proteins with multiple biofunctional domains present a promising strategy for GelMA functionalization, enhancing its biological properties. In this study, we developed a rationally designed recombinant collagen-like protein (RC) engineered with multiple biofunctional domains, which demonstrated the ability to upregulate collagen 1α (COL-1α) expression in NIH-3 T3 cells. By utilizing EDC/NHS chemistry, the purified RC was conjugated to GelMA, resulting in GelMA-RC hydrogels that significantly improved cell viability and migration compared to unmodified GelMA. Subsequent in vivo studies showed that RC-modified GelMA exhibited superior wound healing efficacy, largely attributed to enhanced expression of cytokeratin-14 (CK-14) and COL-1α. These findings underscore the potential of RC-functionalized GelMA in promoting diabetic wound repair and suggest broader applicability for functionalizing other biomaterials.

Oxygen-generating hydrogels combined with electrical stimulation: A dual approach for promoting diabetic wound healing

Chronic wounds resulting from hyperglycemia and hypoxia are common complications in diabetic patients, posing significant challenges for clinical treatment. In this study, we developed a hydrogel (PVNP-SP) using [VBIM]Br, NIPAM, PEGDA, and spirulina, which exhibited strong antioxidant properties. The incorporation of [VBIM]Br endowed the hydrogel with electrical conductivity, allowing it to activate voltage-gated ion channels under an external electric field, thereby promoting cell survival and migration. The hydrogel also enhanced cellular antioxidant capacity by providing sustained oxygenation, inhibiting HIF-1α nuclear translocation, and activating the Nrf2/HO-1 pathway. Notably, in a chronic wound model, the combined effects of oxygen production and electrical stimulation from the PVNP-SP hydrogel significantly reduced wound inflammation, promoted collagen deposition and angiogenesis, and facilitated early wound closure. This therapeutic strategy, which mitigates hypoxia while integrating electrical stimulation, offers a highly effective strategy for improving chronic wound healing in diabetic patients. Statement of significanceInspired by photoautotrophic organisms, we combined microalgae with a conductive hydrogel and we demonstrated the synergistic promotion of chronic wound healing by electrical stimulation combined with microalgae oxygen-producing hydrogel. The approach of combining microalgae hydrogel patches with electrical stimulation demonstrates the feasibility of delivering oxygen to tissues while combining electrical stimulation for synergistic tissue repair. The hydrogel is easy to fabricate and handle, and may be suitable for a variety of treatments, such as myocardial infarction, lower limb ischemia, and drug delivery. The potential applicability of this hydrogel in a variety of treatments suggests that it has promising applications in regenerative medicine.

Inflammation-Modulating Biomedical Interventions for Diabetic Wound Healing: An Overview of Preclinical and Clinical Studies

Inflammation-Modulating Biomedical Interventions for Diabetic Wound Healing: An Overview of Preclinical and Clinical Studies

Literature Review on the Effectiveness of Modern Dressing in the Wound Care Process on Diabetic Wound Healing

Background: Diabetes mellitus is a health problem due to insulin deficiency or insulin resistance that causes high blood glucose. A frequent complication is diabetic ulcer, which is a condition of partial or complete tissue deformity. If it does not get proper treatment, it is very risky to get an infection that leads to amputation.Diabetes Mellitus (DM) has become a prevalent disease, imposing a significant burden on public health due to its widespread occurrence and association with numerous disabilities and fatalities. Uncontrolled DM can lead to severe metabolic complications and long-term vascular issues, including microangiopathy and macroangiopathy. Additionally, individuals with DM are highly susceptible to foot infections, which can escalate into gangrene if not properly managed. Purpose: To determine the effectiveness of modern dressing in the wound care process on diabetic wound healing. Methods: Data collection used descriptive analysis and literature study. The databases used were PubMed, CINAHL, ProQuest and Web of Science. Journal inclusion criteria used PICO and article analysis was conducted by 6 authors. Findings: The evaluated article's findings elucidate the patient's degree of comfort and the more important healing process. It has been demonstrated that contemporary wound care applications make patients feel more at ease as their wounds heal, greatly aiding nurses in nursing care. Modern wound care is a practice that will evolve in response to advancements in nursing science; in this instance, it centers on how comfortable patients are while obtaining wound care-related medical treatments. Therefore, nurses must advance the knowledge behind the use of contemporary wound care to promote patient comfort and hasten the healing process. Conclusion: Modern wound care enhances patient comfort and accelerates healing, greatly supporting nursing practice. With evolving knowledge in nursing science, nurses need to master these methods to maximize patient comfort and recovery in wound care

Effectiveness of Wound Irrigation Using Hypochlorous Acid Liquid on Healing of Diabetic Foot Wounds

Background: Wound cleansing is crucial in wound healing, depending on the method and type of solution used. Hypochlorous Acid is one of the wound irrigation options that can be applied in this process. Objective: This study aims to evaluate the effectiveness of wound irrigation using Hypochlorous Acid (HOCL) on diabetic foot wound healing. Methods: This quantitative research employs a quasi-experimental design, involving 13 diabetic foot wound patients selected through total sampling. Interventions were conducted over five weeks, totaling ten sessions. The Bates-Jensen Wound Assessment Tool (BJWAT) was utilized to assess wound healing, and data were analyzed using SPSS 25, applying paired T-tests to evaluate pre-and post-intervention differences. Results: A statistically significant improvement in diabetic foot wound healing was observed, marked by a p-value = 0.000, highlighting the potential of HOCL in promoting effective wound healing. Conclusion: HOCL wound irrigation significantly enhances diabetic foot wound healing

Biomimetic Triplet Messenger RNA Formulation in MXene Hydrogel Microneedles for Wound Healing

ABSTRACTMessenger RNA (mRNA) has demonstrated immense potential in disease therapeutic applications. The current direction is focused on imparting mRNA with competitive synthetic functions and delicate carrier systems. Here, inspired by the collaborative regulation of growth factors by the cellular microenvironment, we present novel transition metal carbide/nitride (MXene) hydrogel microneedles loaded with a biomimetic triplet mRNA formulation (TM) for diabetic wound treatment. Such microneedles were composed of TM, MXene, and hyaluronic acid hydrogel. The presence of MXene imparted the microneedles with great photo‐thermal responsiveness properties, thus realizing controlled active release by the shrinkage/swelling of hydrogel. With the effective release of TM, the microneedles were proven to enhance endothelial cell migration, growth, and angiogenesis. Through in vivo animal experiments, we have confirmed that TM‐microneedles (TM‐MNs) can promote tissue regeneration and collagen deposition more effectively than intravenous and intradermal administration. Thus, we believe that the proposed TM‐MN platform with precise delivery and controllable release of TM will show great potential for promoting the healing of clinic diabetic wounds.

Quercetin@β-Cyclodextrin Conjugated Keratin/Polyurethane Biocomposite Mats for Infected Diabetic Wound Healing.

Chronic diabetic wounds suffer from severe complications caused by long-term high levels of oxidative stress and bacterial infection. Quercetin (Que) has excellent anti-inflammatory, antioxidant, and antibacterial activity, making it a promising drug to address the above issues. To exploit the benefits of Que in a more effective and sustained way to treat diabetic wounds, carboxymethyl β-cyclodextrin (CMCD) was synthesized and conjugated to keratin, then complexed with Que to form Que@Ker-CMCD inclusion, followed by electrospinning with polyurethane (PU) to afford Que@Ker-CMCD/PU mats. The approach significantly enhanced water solubility, bioavailability, and sustained release of Que. Crucially, these mats exhibited robust antioxidant and antibacterial activities. Moreover, the mats fostered an environment conducive to cell proliferation, migration, angiogenesis, and re-epithelialization, pivotal processes in wound healing and remodeling. Consequently, a marked acceleration in remodeling chronic diabetic wounds was observed. In conclusion, this study introduces a novel therapeutic strategy that not only harnesses the multifaceted benefits of Que but also enhances its delivery and performance, offering a promising avenue for the effective treatment of chronic diabetic wounds.

A tranexamic acid-functionalized acellular dermal matrix sponge co-loaded with magnesium ions: Enhancing hemostasis, vascular regeneration, and re-epithelialization for comprehensive diabetic wound healing

Excessive inflammation, accumulation of wound exudate, and blood seepage are common in diabetic wounds, hindering cell proliferation and disrupting tissue remodeling, leading to delayed healing. This study presents a multifunctional sponge scaffold (P5T3@Mg) created by combining an acellular dermal matrix with tranexamic acid and MgO nanoparticles, designed for hemostatic and anti-inflammatory effects. The P5T3@Mg scaffold effectively absorbs wound fluid while promoting healing. In vivo and in vitro hemostasis experiments demonstrate that the P5T3@Mg sponge exhibits excellent hydrophilicity, enhancing blood absorption at the wound site, inhibiting fibrinolysis, and expediting hemostasis. Additionally, the sustained release of Mg2+ from the P5T3@Mg sponge promotes collagen deposition and angiogenesis in diabetic rat wounds, suppressing chronic inflammation and accelerating tissue remodeling and repair.

Exos-Loaded Gox-Modified Smart-Response Self-Healing Hydrogel Improves the Microenvironment and Promotes Wound Healing in Diabetic Wounds.

Wound management has always been a challenge in the clinical treatment of diabetes. In this study, glucose oxidase (GOx) is grafted onto natural pullulan polysaccharides, and oxidization is carried out to form a self-healing hydrogel using carboxymethyl chitosan by means of reversible Schiff base covalent bonding. The smart-response drug release properties of this natural self-healing hydrogel are demonstrated in diabetic wounds by taking advantage of two key factors, namely the pH-responsive nature of Schiff base bonding and the fact that GOx reduces the pH in diabetic wounds. To further enhance the biological functions of the hydrogel dressing, exosomes (Exos) are introduced into the hydrogel system. The GOx present in the hydrogel system improves the high-glucose microenvironment of diabetic wounds, releasing H2O2 to impart antimicrobial effects, and ensuring that the hydrogel realizes a smart-response function. The carboxymethyl chitosan component used to construct the hydrogel plays an effective antibacterial role. Moreover, the Exos loaded into the hydrogel effectively promotes neovascularization of the wound. The Exos also regulates macrophage polarization and reduces the levels of persistent inflammation in diabetic wounds. These results suggest that this smart responsive, multifunctional, and self-healing hydrogel dressing is ideal for the management of diabetic wounds.