Diabetic Wound Healing Research Articles

Macrophages: Key players in diabetic wound healing

In this editorial, we discuss the article by Wen et al published. Diabetic foot ulcers are prevalent and serious complications of diabetes, significantly impacting patients’ quality of life and often leading to disability or death, thereby placing a heavy burden on society. Effective diabetic wound healing is hindered by an imbalance in macrophage polarization; many macrophages fail to transition from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, which is crucial for tissue remodelling and repair. The wound healing process is both dynamic and complex. Healthy M1 macrophages, which have strong phagocytic abilities, are vital during the inflammatory phase of diabetic wound healing. However, the failure to transition to M2 macrophages during the proliferative phase hinders wound healing. We anticipate the development of new therapies that can repair damaged M1 macrophages during the inflammatory phase and promote M2 macrophage polarization during the proliferative phase, thereby enhancing the overall healing process.

Pluripotent polysaccharide coordinated hydrogels remodel inflammation, neovascularization and reepithelization for efficient diabetic wound prohealing.

Chronic diabetic wounds seriously threaten the health and life of human beings, however, it is challenging to develop pluripotent dressings that comprehensively remodel inflammation microenvironment, neovascularization and reepithelization to achieve high performance healing in diabetic wounds. Herein we construct a bioinspired polysaccharide coordinated hydrogel composed of bisphosphate-modified β-glucan (BG) with bioactive metal ions of Zn2+ and Mg2+, in which multiple chelation enables fast gelation, self-healing, and dynamically sealing wounds. In vitro Mg2+ release from BGM or BGMZ could promote intracellular uptake of Zn2+ through upregulating Zn2+-related transporter protein ZIP6 while intracellular Mg2+ remained relatively stable via downregulating the Mg2+ transporter protein of MagT1. The screened lead hydrogel BGMZ could substantially polarize proinflammatory M1 to prohealing M2 phenotypes by the main BG-downregulating NF-kB signaling pathway, and both Mg2+ and Zn2+ release from BGMZ synergistically promoted proliferation and angiogenesis by upregulating PI3K/Akt signaling pathway, facilitating the reepithelization and tissue remodeling. Remarkably, single BGMZ treatment performed full-thickness wound closure, fast granulation and dermis regeneration, optimal neovascularization and reepithelization, high levels of overall collagen and fibrous collagen-I, and dense hair follicles, thus achieving high performance prohealing in diabetic wounds. Consequently, this study opens a new avenue to design pluripotent polysaccharide hydrogel dressing for structures and functions remodeling of chronic and diabetic wounds.

Loureirin B Accelerates Diabetic Wound Healing by Promoting TGFβ/Smad-Dependent Macrophage M2 Polarization: A Concerted Analytical Approach Through Single-Cell RNA Sequencing and Experimental Verification.

Diabetic wound (DW) represent a significant clinical challenge and often fail to heal effectively. Loureirin B (LB), a flavonoid extracted from dragon's blood, has shown potential by influencing macrophage polarization and promoting wound healing. However, its mechanisms and efficacy in DW remain to be explored. This study employed single-cell RNA sequencing to analyze the classification of cells in diabetic foot ulcers and to identify the related mechanisms influenced by macrophages. Molecular docking was used to predict the interactions of LB with key proteins in the TGFβ/Smad signaling pathway. The effects of LB on macrophage polarization and wound healing were further validated through invitro and invivo experiments using a DW model. Single-cell analysis identified specific macrophage subtypes involved in the DW healing process and highlighted the role of the TGFβ/Smad pathway. Molecular docking suggested the potential action within the TGFβ/Smad pathway. Invitro studies showed that under high glucose conditions, LB promoted macrophage polarization from pro-inflammatory M1 to healing-promoting M2 and ECM production in fibroblasts by activating TGF-β/Smad signaling. Invivo, LB treatment enhanced wound healing rates in diabetic mice and promoted macrophage M2 polarization and fibroblast synthesis of ECM by activating TGF-β/Smad signaling. LB regulates macrophage M2 polarization and fibroblast synthesis of ECM by activating TGF-β/Smad signaling to promote DW healing. These findings suggest that LB could be a potential therapeutic agent for improving DW healing, emphasizing the need for further clinical studies to explore its efficacy and mechanisms in human subjects.

A microenvironment-modulating dressing with proliferative degradants for the healing of diabetic wounds.

Diabetic wounds are usually entangled in a disorganized and self-perpetuating microenvironment and accompanied by a prolonged delay in tissue repair. Sustained and coordinated microenvironment regulation and tissue regeneration are key to the healing process of diabetic wounds, yet they continue to pose a formidable challenge. Here we report a rational double-layered dressing design based on chitosan and a degradable conjugated polymer polydiacetylene, poly(deca-4,6-diynedioic acid) (PDDA), that can meet this intricate requirement. With an alternating ene-yne backbone, PDDA degrades when reacting with various types of reactive oxygen species (ROS), and more importantly, generates proliferative succinic acid as a major degradant. Inheriting from PDDA, the developed PDDA-chitosan double layer dressing (PCD) can eliminate ROS in the microenvironment of diabetic wounds, alleviate inflammation, and downregulate gene expression of innate immune receptors. PCD degradation also triggers simultaneous release of succinic acid in a sustainable manner, enabling long-term promotion on tissue regeneration. We have validated the biocompatibility and excellent performance of PCD in expediting the wound healing on both diabetic mouse and porcine models, which underscores the significant translational potential of this microenvironment-modulating, growth-promoting wound dressing in diabetic wounds care.

Broad-Spectrum Bactericidal Multifunctional Tiny Silicon-Based Nanoparticles Modified with Tannic Acid for Healing Infected Diabetic Wounds.

Infected chronic wounds, in particular, diabetic wounds, are hard to heal, posing a global health concern with high morbidity and mortality rates. Diabetic full-thickness wounds infected with E. coli belong to the most difficult to heal chronic infected wounds. Here, we introduced tannic acid-modified silicon-based nanoparticles (TA-SiNPs) with broad-spectrum bactericidal activity that bacteria develop minimal resistance to, and they can effectively treat full-thickness wounds in diabetic mice infected with E. coli. Our findings indicate that these TA-SiNPs could achieve 100% antibacterial efficiency against S. aureus and 99.83% against E. coli, underlied by a positive surface charge and tannic acid groups facilitating bacterial membrane chemical composition depletion and depolarization of the membrane. In addition, we showed that spraying TA-SiNPs onto the skin wound of diabetic mice infected with E. coli resulted in wound healing with 98% closure after 12 days, in stark contrast to 49% of the control (PBS) and 68% of the one treated with Ofloxacin. Along with infection inhibition and ROS scavenging, we identified cell proliferation stimulation, inflammatory cytokine downregulation, and healing cytokine upregulation in the lesion, favoring the healing process. This study not only demonstrates the feasibility of employing silicon-based nanoparticles in diabetic wound healing for the first time, but also reports the first broad-spectrum bactericidal silicon nanodots. Furthermore, this provides novel insights into the mechanism of tannin-based nanoparticles disrupting bacterial membranes by depleting their chemical constituents. Our results highlighted that the developed TA-SiNPs are an effective nanomaterial for treating the infected chronic wounds.

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.

FORMULATION, CHARACTERIZATION AND OPTIMIZATION OF PLGA-CHITOSAN-LOADED FATTY ACID SCAFFOLDS FOR THE TREATMENT OF DIABETIC WOUNDS

Objective: The objective of the current research to formulate Eicosapentanoic Acid/Decosahexanoic Acid (EPA/DHA)incorporated into Chitosan (CS)and Poly-Lactic-Glycolic Acid (PLGA), nanoparticles composite scaffolds to the accelerated diabetic wound healing. The main focus of this present research is to evaluate and develop the chitosan–PLGA biodegradable polymer scaffolds loaded with long-chain omega-3 Polyunsaturated Fatty Acids (PUFA’s) (EPA/DHA). Methods: Nano scaffolds were prepared by solvent evaporation method loaded with CS-PLGA, EPA and DHA to treat diabetic wounds at targeted site as pharmacotherapeutically. Upon investigation, the developed biodegradable crosslinked scaffold possesses matrix degradation, optimal porosity, prolonged drug release action than the non-cross linked scaffold. The prepared formulation containing CS-PLGA loaded with EPA/DHA were formulated as nanoscaffold for wound topical applications was carried out by using freeze drying process. Results: The prepared CS-PLGA nano scaffolds were optimized and evaluated for physicochemical properties, dynamic light scattering with a particle size of 248 nm and zeta of-24mVand Scanning Electron Microscopy (SEM) were found to be spherical. In addition, the optical properties of EPA/DHA and PLGA, along with CS, can be compared by examining their absorption and wavelength (nm) using UV-visible spectroscopy. The structural and functional groups of the prepared end products were characterized by Fourier-Transformed Infrared Spectroscopy (FT-IR) has shown good compatibility with excipients and nanoformulaton, in vitro drug release studies done by using dialysis bag membrane results find that first-order Higuchi model was followed showing 20% release in first 0.2 h. MTT(3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide) assay was carried out and it showed that both crosslinked and non-crosslinked scaffolds(110 and 120%) improved cell growth when compared to control (100%). Conclusion: Finally, the results showed that the PLGA, CS nanoscaffolds containing 98% of PUFA’s (EPA/DHA) have increased in proinflammatory cytokines production at the particular wound site and thus accelerated healing activity, depending on the pre-clinical studies have trespassed, the therapeutic potential to penetrating at wound site. The optimized nanoformulation could be a better formulation for targeting and treatment of diabetic wounds at an optimal ratio.

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.

Carboxymethyl chitosan and sodium alginate oxide pH-sensitive dual-release hydrogel for diabetes wound healing: The combination of astilbin liposomes and diclofenac sodium

Difficulty in diabetic wound healing presents a significant challenge in clinical practice. This study developed a hydrogel utilizing oxidized sodium alginate (OSA) and carboxymethyl chitosan (CMCS) as the matrix. Astilbin (ASB), known for its antioxidant properties, was incorporated into Astilbin liposome (AL) using a thin film dispersion method. Diclofenac sodium (DS) and AL, both possessing anti-inflammatory properties, were then encapsulated in the hydrogel to create a pH-responsive dual-release system for topical application to expedite diabetic wound healing. Results from the research demonstrate that the composite hydrogel exhibits favorable biodegradability, stable rheology, and swelling capacity, facilitating the controlled release of AL and DS. In vivo and in vitro data demonstrated that the hydrogel was biocompatible and anti-inflammatory, antibacterial and homeostatic, and significantly promoted the process of inflammation suppression, angiogenesis and fibrotic repair of wounds. In conclusion, this novel hydrogel provides a simple and effective method for the repair of chronic diabetic wounds.

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.

Antibacterial carboxymethyl chitosan hydrogel loaded with antioxidant cascade enzymatic system for immunoregulating the diabetic wound microenvironment

Diabetic wound healing faces several complex challenges, such as hypoxia, oxidative stress, and bacterial infections, which severely inhibit the wound-healing process. Herein, a quaternary ammonium salt-crosslinked carboxymethyl chitosan hydrogel (TPC) with excellent antioxidant and antibacterial properties was developed to immunoregulate the diabetic wound microenvironment. The TPC hydrogel was prepared by first mixing carboxymethyl chitosan (CMCS) and protocatechualdehyde (PA), followed by the addition of a quaternary ammonium cross-linker (TSPBA) and a superoxide dismutase (SOD)–catalase (CAT) cascade system. The immobilized SOD and CAT retained their activity, continuously converting endogenous ·O2− and H2O2 to O2 and H2O. PA also provided the TPC hydrogel excellent oxygen and nitrogen radical scavenging capacity. The quaternary ammonium groups in TSPBA significantly enhanced the inherent antibacterial ability of CMCS-based hydrogels. In diabetic wound-healing experiments, this porous and adhesive TPC hydrogel effectively closed wounds and regenerated skin tissue, resulting in shorter wound edges, thicker granulation, and higher collagen deposition levels compared with other groups. The TPC hydrogel also promoted macrophage polarization toward the M2 phenotype, accelerating wound healing by upregulating IL-10 expression, downregulating IL-6 expression, and enhancing angiogenesis. These results demonstrate the great potential of TPC hydrogel as a promising therapeutic dressing for treating 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.

Self-healing Ppy-Hydrogel Promotes Diabetic Skin Wound Healing through Enhanced Sterilization and Macrophage Orchestration Triggered by NIR

Self-healing Ppy-Hydrogel Promotes Diabetic Skin Wound Healing through Enhanced Sterilization and Macrophage Orchestration Triggered by NIR

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.