Promote Wound Repair Research Articles

A chitosan-optimized polyethyleneimine/polyacrylic acid multifunctional hydrogel for reducing the risk of ulcerative arterial bleeding.

Ulcerative arterial bleeding is characterized by sudden onset, rapid disease development, and high mortality, which is a great challenge for clinicians to treat, specially bleeding in areas where endoscopic operation is difficult, or in the case of diffuse bleeding, tumor bleeding, and recurrent bleeding. Herein, we proposed a novel treatment strategy using biomaterials to protect the wound and isolate the erosion of digestive tract contents to prevent arterial bleeding in advance. By introducing chitosan to construct multihydrogen-bonding and an electrostatic interaction system, we developed polyethyleneimine/polyacrylic acid/chitosan (PEI/PAA/CS) multifunctional hydrogel. The new hydrogel is characterized by ultrafast gelation, strong tissue adhesion, gastric acid resistance, burst resistance, biocompatibility, hemostasis, and tissue repair. The addition of CS significantly improved the tissue adhesion, biocompatibility, hemostasis, and tissue repair ability of the hydrogel. The PEI/PAA/CS hydrogel could adhere to the ulcer surface and form a protective layer on the wound to prevent arterial bleeding. Importantly, the PEI/PAA/CS hydrogel also has the ability to stop bleeding and promote wound repair, which has been demonstrated in a variety of hemorrhage models in rats and rabbits. All of these factors indicate that the PEI/PAA/CS hydrogel is a promising biomaterial for reducing the risk of ulcerative arterial bleeding.

Self-Healing Supramolecular Hydrogels with Antibacterial Abilities for Wound Healing.

Wound healing due to skin defects is a growing clinical concern. Especially when infection occurs, it not only leads to impair healing of the wound but even leads to the occurrence of death. In this study, a self-healing supramolecular hydrogel with antibacterial abilities was developed for wound healing. The supramolecular hydrogels inherited excellent self-healing and mechanical properties are produced by the polymerization of N-acryloyl glycinamide monomers which carries a lot of amides. In addition, excellent antibacterial properties are obtained by integrating silver nanoparticles (Ag NPs) into the hydrogels. The resultant hydrogel has a demonstrated ability in superior mechanical properties, including stretchability and self-healing. Also, the good biocompatibility and antibacterial ability have been proven in hydrogels. Besides, the prepared hydrogels were employed as wound dressings to treat skin wounds of animals. It was found that the hydrogels could significantly promote wound repair, including relieving inflammation, promoting collagen deposition, and enhancing angiogenesis. Therefore, such self-healing supramolecular hydrogels with composite functional nanomaterials are expected to be used as new wound dressings in the field of healthcare.

Facile synthesis of hydroxypropyl chitosan-egg white hydrogel dressing with antibacterial and antioxidative activities for accelerating the healing of burn wounds.

Burn injury is the fourth most common injury worldwide. Deep partial-thickness burns are susceptible to bacterial infections due to the absence of a skin shield, which can lead to severe pain, scarring, and even death. Therefore, developing a wound dressing that can promote wound repair accompanied by excellent antibacterial effects is crucial for clinical application. Herein, a facile self-healing hydroxypropyl chitosan-egg white hydrogel (HPCS-EWH) with excellent biocompatibility, antioxidant activity, anti-inflammation and antibacterial properties was prepared. This physical crosslinking hydrogel was endowed with the intrinsic merits of its parental components, such as reactive oxygen species (ROS) scavenging, antibiosis, and thriving cell growth in vitro. In an in vivo model of Staphylococcus aureus-infected burn wounds, HPCS-EWH could accelerate wound healing due to its anti-inflammatory and antibacterial activities, and promote cell proliferation and angiogenesis. Therefore, HPCS-EWH could be used to heal deep partial-thickness skin burn wounds.

Progress on the mechanism and application of adipose-derived stem cells in promoting wound repair

Chronic refractory wounds and scars caused by abnormal wound repair seriously damage the health of patients and affect their quality of life. At present, there is a lack of simple but effective and economical treatment methods. Adipose-derived stem cells (ASCs), as a kind of mesenchymal stem cells with multi-directional differentiation potential, have been confirmed by several in vivo and in vitro studies to promote wound healing by promoting epithelialization, angiogenesis, immunoregulation, antioxidant properties, and other mechanisms. ASCs and their derivatives have been used in the treatment of refractory wounds caused by burns, diabetic, and radiation injuries with good results achieved. Their potential to become new materials for wound repair has also been confirmed. This paper reviewed the mechanism and clinical application of ASCs in promoting wound repair, and looked into its research direction and prospects.

Exosomes of Adipose Tissue-Derived Stem Cells Promote Wound Healing by Sponging miR-17-5p and Inducing Autophagy Protein Ulk1.

Wound healing undergoes intricate phases: hemostasis, inflammation, proliferation, and remodeling. Stem cell therapy based on adipose tissue-derived stem cell exosomes (ADSCs-exo) is considered a potential effective treatment for accelerating wound healing. However, the molecular mechanisms of wound healing using ADSCs-exo remain largely unknown. Circular wounds, 1 × 1 cm, were generated on C57BL/6 mice, followed by OriCell C57BL/6 mouse adipose-derived mesenchymal stem cell suspension treatment, and wound area was measured and recorded at days 0, 7, and 21, respectively. A comprehensive transcriptome profiling of skin wounds was conducted in the mouse model. Importantly, the authors also examined autophagy and cell migration in mouse keratinocytes treated with ADSCs-exo. Further competing endogenous RNA networks were also used to reveal the relationship between Neat1 and Ulk1 . Mouse keratinocytes treated with ADSCs-exo showed significant up-regulation of pathways related to wound healing, including response to virus, bacterium, immune system, and wounding. Activated autophagy was detected, which significantly promoted the wound repair of mice. Competing endogenous RNA networks uncovered that Neat1 induces the expression of Ulk1 and thus up-regulates autophagic activity to promote wound repair through sponging miR-17-5p. Collectively, these results reveal a novel molecular mechanism that the autophagy pathway enhanced by the Neat1 /miR-17-5p/ Ulk1 axis can promote the wound healing and suggest that long noncoding RNA Neat1 loaded by ADSCs-exo might be a potential therapeutic target for skin nonhealing wounds. This study may provide new clues for the applications of ADSCs-exo in skin wounds and promote the development of ADSCs-exo therapy in clinical treatment of skin wounds.

Concentrated Growth Factor Promotes Wound Healing Potential of HaCaT Cells by Activating the RAS Signaling Pathway.

The aim of this study was to explore the effect of concentrated growth factor (CGF) on the wound healing potential of human epidermal cells (HaCaT) in vitro and in vivo. CGF was extracted from venous blood using the centrifugal separation method. The CGF-conditioned medium was prepared from CGF gel immersed in Dulbecco's Modified Eagle medium. Crystal violet staining and wound healing assay were used to evaluate the proliferation and migration of HaCaT cells, respectively. Lipopolysaccharide (LPS) was used to test the anti-inflammatory function of CGF. An ELISA kit was employed to detect the concentration of growth factors and interleukins in CGF medium. mRNA and protein levels of angiogenic biomarkers (Angiopoietin-1 (ANGPT-1), vascular endothelial growth factor-A (VEGF-A) and Angiopoietin-2 (ANGPT-2) ) were determined by quantitative polymerase chain reaction (qPCR) and Western blot, respectively. A dorsal excisional wound model was recruited to test the wound healing effect of CGF in mice. Three-day treatment of HaCaT cells with CGF significantly promoted cell proliferation, which was followed by an increase in Vascular Endothelial Growth Factor (VEGF) and Fibroblast Growth Factor (FGF) levels in the medium. Cytokines (IL-6, IL-8 and TNF-α) were increased in LPS-stimulated HaCaT cells after 3 days, and CGF slightly inhibited the mRNA expression of these cytokines. The RAS signaling pathway was activated upon CGF treatment. Both RAS knockdown and an inhibitor of RAS (zoledronic acid) could block the migration of HaCaT cells after CGF treatment. Protein expressions of CD31, ANGPT-1, and VEGF-A were up-regulated in a dose-dependent manner upon CGF exposure. The protein level of ANGPT-2 was down-regulated after CGF treatment. CGF could promote wound healing in vivo, as demonstrated using the full skin defect model in nude mice. CGF was shown to promote wound repair in vitro and in vivo. The RAS cell signaling pathway was responsible for CGF stimulating the wound healing potential of HaCaT cells.

GDF15 alleviates the progression of benign tracheobronchial stenosis by inhibiting epithelial-mesenchymal transition and inactivating fibroblasts

Benign tracheobronchial stenosis (BTS) is a fatal and incurable disease. Epithelial repair and matrix reconstruction play an important role in the wound repair process. If the interstitial context is not restored and stabilized in time, it can lead to pathological fibrosis. Here we attempted to identify cytokines that are involved in promoting wound repair. Growth differentiation factor 15 (GDF15) is a cytokine secreted by tracheal epithelial cells, which is indispensable for the growth of epithelial cells and inhibits the overgrowth of fibroblasts. GDF15 can counteract transforming growth factor-β (TGFβ1) stimulation of epithelial-mesenchymal transition (EMT) in tracheal epithelial cells and inhibit fibroblast activation via the TGFβ1-SMAD2/3 pathway. In a rat model of tracheal stenosis, GDF15 supplementation alleviated the degree of tracheal stenosis. These results suggest that GDF15 prevents fibroblast hyperactivation and promotes epithelial repair in injured trachea. GDF15 may be a potential therapy to improve benign tracheobronchial stenosis.

Mussel-inspired hydrogel with injectable self-healing and antibacterial properties promotes wound healing in burn wound infection

Burn wound infections cause serious problems for public health. More than 180,000 patients die from burns every year worldwide. In addition, the difficulty of healing wounds and wound infections caused by burns affects the mental health of patients. Therefore, it is very important to develop a wound dressing that can promote wound repair and exhibits good antibacterial effects. Here, we used oxidized konjac glucomannan (OKGM), γ-poly(glutamic acid) modified with dopamine and L-cysteine (γ-PGA-DA-Cys) and ε-polylysine (ε-PL) to produce an OKGM/γ-PGA-DA-Cys/ε-PL (OKPP) hydrogel. This hydrogel was produced by thiol-aldehyde addition and Schiff-base reactions and has the ability to be injected and self-heal. The results showed that the hydrogel exhibits good antibacterial effects on Pseudomonas aeruginosa and Staphylococcus aureus and has antioxidant effects in vitro. Moreover, the hydrogel also exhibits good adhesion. In a burn wound infection model, the hydrogel promoted wound healing and reduced the production of inflammation. These results proved that the hydrogel has clinical potential as a wound dressing for burn wound infection.

Highly Antibacterial and Adhesive Hyaluronic Acid Hydrogel for Wound Repair.

Bacterial infections accompanied with wound healing often lead to more serious health hazards to patients. Therefore, it is urgent to explore a wound dressing that can promote wound repair while possessing antibacterial capability. Here, we constructed a multifunctional hydrogel dressing by a redox-initiated cross-linking reaction of methacrylated hyaluronic acid (HAMA), 5,10,15,20-tetra (4-methacrylate phenyl) porphyrin (TPP), and dopamine methacrylamide (DMA), named HAMA-TPP-DMA, with broad-spectrum photodynamic antibacterial capability, where the aggregation of TPP photosensitizer units could be greatly inhibited to produce more singlet oxygen. The hydrogel has excellent biodegradability and biocompatibility, providing favorable conditions for wound healing. Furthermore, the incorporation of dopamine into the hydrogel gives the wound dressing with enhanced adhesiveness, benefiting for the wound repair. More importantly, the antibacterial experiments in vitro and mice wound models in vivo showed that the HAMA-TPP-DMA hydrogel can significantly resist bacteria and accelerate the wound healing in mice (the closure rate > 98% after 15 days). Thus, this hydrogel dressing with superior antibacterial infection and wound healing capability provides a promising strategy in wound repair.

Effects of Human Fibroblast-Derived Multi-Peptide Factors on the Proliferation and Migration of Nitrogen Plasma-Treated Human Dermal Fibroblasts.

Human fibroblast-derived multi-peptide factors (MPFs) promote wound repair by playing crucial roles in cell recruitment, adhesion, attachment, migration, and proliferation. Cultured human dermal fibroblasts (HDFs) were directly treated with non-contact low- and high-energy nitrogen plasma and further cultured in various conditioned media. Cell proliferation and wound-healing properties were evaluated. In Opti-modified Eagle's medium + GlutaMAX culture, reduced HDF viability was observed 24 h after 2-J/pulse plasma treatment and 12 and 24 h after 3-J/pulse treatment. Meanwhile, in dermal fibroblast-conditioned medium (DFCM) containing MPF culture, reduced HDF viability was observed only 24 h after 3-J/pulse treatment. Under DFCM-MPF culture, the wound area percentage was significantly decreased after 12 and 24 h in untreated HDFs; at 9, 12, and 24 h after 1-J/pulse plasma treatment; at 3, 6, 9, 12, and 24 h after 2-J/pulse plasma treatment; and at 9, 12, and 24 h after 3-J/pulse plasma treatment. Greater migration of HDFs with or without plasma treatment was found in DFCM-MPFs than in other conditioned media. Low-energy nitrogen plasma treatment promotes HDF proliferation and wound repair. DFCM-MPFs enhanced cell proliferation and improved the wound healing properties of HDFs treated with low- and high-energy plasma.

Application of recombinant human basic fibroblast growth factor in repair of the aged dog bite wound

BackgroundDog bite wounds usually have severe local soft tissue damage and the wounds are likely to be contaminated by a large number of bacteria or even a series of rare pathogenic bacteria, leading to repeated infection and delayed wound healing. Recombinant human basic fibroblast growth factor (rh-bFGF) has excellent ability to promote wound repair and widely used in various complicated wounds. ObjectiveObserve the clinical efficacy of Recombinant human basic Fibroblast growth factor (rh-bFGF) applicated in the treatment of dog bite wounds. MethodsA total of 31 patients (16 adult and 15 aged) with rabies exposure grade Ⅲ dog bite wounds treated in the department of emergency surgery in our hospital from February 2020 to February 2022 were reviewed. Rh-bFGF was applied in the wounds after debridement and the patients were treated with preventive anti-inflammatory therapy. Observe the wound healing rules, infection rate, related complications and application time of antibiotics. ResultsEventually, all the wound were well healed and the healing time needed for most patients were about 2–3 weeks. The wound infection rate of aged patients was much higher, therefore application time of intravenous antibiotics injection in the aged patients was significantly higher than it in the adults (P < 0.05), but the difference of the time reach the intermittent wound dressing change was not statistically significant (P > 0.05). ConclusionRh-bFGF is safe and reliable for severe dog bite wounds in both the elderly and adults, it may help improve the early stage healing speed of aged patients, but the specific treatment needs to be individualized and accurate depends on different personal physique and wound conditions.

In situ monitoring and regulation of local reactive oxygen species levels to promote wound repair

Local oxidative stress and inflammatory response are the essential procedures in wound repair, which determine the progress, prognosis, and quality of wound repair. Reactive oxygen species is one of the important indexes reflecting oxidative stress and inflammatory response of body, which is considered as a promising target to be regulated in wound inflammation. Recently, with the rapid development of nanomedicine, our research group and other research groups have successfully developed various diagnosis and treatment reagents for reactive oxygen species through interdisciplinary integration, to monitor and regulate reactive oxygen species in wounds in real time, and to finally achieve the goal of improving the speed and quality of wound repair, thus providing a new strategy and direction for the diagnosis and treatment of local inflammatory response in wounds. This article summarizes reactive oxygen species as the regulatory target of local inflammatory response in wounds, in situ monitoring and precise regulation of reactive oxygen species.

Exosomes from Adipose Stem Cells Promote Diabetic Wound Healing through the eHSP90/LRP1/AKT Axis.

Oxidative damage is a critical cause of diabetic wounds. Exosomes from various stem cells could promote wound repair. Here, we investigated the potential mechanism by which exosomes from adipose-derived stem cells (ADSC-EXOs) promote diabetic wound healing through the modulation of oxidative stress. We found that ADSC-EXOs could promote proliferation, migration, and angiogenesis in keratinocytes, fibroblasts, and endothelial cells. Furthermore, ADSC-EXOs reduced the reactive oxygen species (ROS) levels in these cells and protected them against hypoxic and oxidative stress damage. Finally, the local injection of ADSC-EXOs at wound sites significantly increased collagen deposition and neovascularization while reducing ROS levels and cell death; thus, it led to accelerated diabetic wound closure. The mechanism underlying ADSC-EXO functions involved heat-shock protein 90 (HSP90) expressed on the cell surface; these functions could be inhibited by an anti-HSP90 antibody. Exosomal HSP90 could bind to the low-density lipoprotein receptor-related protein 1 (LRP1) receptor on the recipient cell membrane, leading to activation of the downstream AKT signaling pathway. Knockdown of LRP1 and inhibition of the AKT signaling pathway by LY294002 in fibroblasts was sufficient to impair the beneficial effect of ADSC-EXOs. In summary, ADSC-EXOs significantly accelerated diabetic wound closure through an exosomal HSP90/LRP1/AKT signaling pathway.

Retraction: Metallic ions encapsulated in electrospun nanofiber for antibacterial and angiogenesis function to promote wound repair.

[This retracts the article DOI: 10.3389/fcell.2021.660571.].

Enhanced Carboxymethylcellulose Sponge for Hemostasis and Wound Repair

Skin is the interface between human beings and the outside world. After skin injury, bleeding control and wound protection is urgently needed. In the study, the carboxymethyl cellulose/carboxymethyl chitosan-polydopamine (CMC/CMCS-PDA) sponge is prepared for skin hemostasis and repair. The self-polymerization of dopamine (DA) and cross-linking between DA and CMCS are simultaneously completed by Michael addition reaction to form CMCS-PDA under alkaline conditions. CMCS-PDA is introduced into the CMC sponge by EDC/NHS to improve the hemostasis ability and wound repair. By increasing the dosage of CMCS to get CMC/CMCS-PDA1, CMC/CMCS-PDA2, and CMC/CMCS-PDA3 sponges, and the stability of CMC/CMCS-PDA sponge is improved with the increasing addition of CMCS. Compared with a simple CMC/PDA sponge, CMC/CMCS-PDA sponge has a high hemostatic effect for its dispersion stability and CMC/CMCS-PDA2 exhibits the best hemostatic ability with proper crosslinking. At the same time, the prepared CMC/CMCS-PDA sponge has good antibacterial and antioxidant properties. Rat skin wound model showed that CMC/CMCS-PDA sponge can better promote wound repair. Therefore, CMC/CMCS-PDA sponge could be a potential wound dressing for skin hemostasis and repair.

LPS-pretreatment adipose-derived mesenchymal stromal cells promote wound healing in diabetic rats by improving angiogenesis

Mesenchymal stem cells (MSCs) play a key role in wound healing, and the advantages of pretreated MSCs in wound healing have previously been reported. In the present study, we investigated the impact of LPS pretreated human adipose-derived MSCs on skin wound healing in diabetic rats. We found that some improvements occurred through improving angiogenesis. Then, we scrutinized the impact of lipopolysaccharide (LPS) treatment on human adipose-derived MSCs in a high-glucose (HG) medium, as an in vitro diabetic model. In vivo findings revealed significant improvements in epithelialization and angiogenesis of diabetic wounds which received LPS pre-MSCs. Particularly, LPS pre-MSCs-treated diabetic wounds reached considerably higher percentages of wound closure. Also, the granulation tissue of these wounds had higher pronounced epithelialization and more vascularization compared with PBS-treated and MSCs-treated diabetic ones by CD31, VEGF, CD90, collagen 1, and collagen 3 immunostaining. Western-blots analyses indicated that LPS pre-MSCs led to the upregulation of vascular endothelial growth factor (VEGF) and DNMT1. In addition, significantly higher cell viability (proliferation/colonie), and elevated VEGF and DNMT1 protein expression were observed when MSCs were treated with LPS (10 ng/ml, 6 h) in HG culture media. Based on these findings, it is suggested that LPS pre-MSCs could promote wound repair and skin regeneration, in some major processes, via the improvement of cellular behaviors of MSCs in the diabetic microenvironment. The beneficial advantages of LPS treated with mesenchymal stem cells on wound healing may lead to establishing a novel approach as an alternative therapeutic procedure to cure chronic wounds in diabetic conditions.

Dual-Functional Nanofibrous Patches for Accelerating Wound Healing.

Bacterial infections and inflammation are two main factors for delayed wound healing. Coaxial electrospinning nanofibrous patches, by co-loading and sequential co-delivering of anti-bacterial and anti-inflammation agents, are promising wound dressing for accelerating wound healing. Herein, curcumin (Cur) was loaded into the polycaprolactone (PCL) core, and broad-spectrum antibacterial tetracycline hydrochloride (TH) was loaded into gelatin (GEL) shell to prepare PCL-Cur/GEL-TH core-shell nanofiber membranes. The fibers showed a clear co-axial structure and good water absorption capacity, hydrophilicity and mechanical properties. In vitro drug release results showed sequential release of Cur and TH, in which the coaxial mat showed good antioxidant activity by DPPH test and excellent antibacterial activity was demonstrated by a disk diffusion method. The coaxial mats showed superior biocompatibility toward human immortalized keratinocytes. This study indicates a coaxial nanofiber membrane combining anti-bacterial and anti-inflammation agents has great potential as a wound dressing for promoting wound repair.

Polydopamine-doped supramolecular chiral hydrogels for postoperative tumor recurrence inhibition and simultaneously enhanced wound repair

Cancer recurrence remains a major challenge after primary tumor excision, and the inflammation of tumor-caused wounds can hinder wound healing and potentially promote tumor growth. Herein, a chiral L-phenylalanine-based (LPFEG) supramolecular hydrogel system encapsulated with polydopamine nanoparticles (PDA-NPs) has been developed in order to prevent tumor relapse after surgery and promote wound repair. PDA-NPs allow for near-infrared (NIR) light-triggered photothermal therapy, especially, it can scavenge free radicals in the surgical wound. LPFEG can mimic native extracellular matrix (ECM) structure to create a chiral microenvironment that enhances fibroblast adhesion, proliferation, and new tissue regeneration. With anticancer drug doxorubicin (DOX) loaded into the composite hydrogel, the antitumor effect is significantly enhanced by the integration of chemo-photothermal therapy both in vitro and in vivo. The PDA-based chiral supramolecular composite hydrogel as an effective postoperative adjuvant possesses promising applicable prospects in inhibiting tumor recurrence and accelerating wound healing after operation. Statement of SignificanceAfter primary tumor excision, cancer recurrence remains a severe concern, and the inflammation induced by tumor-related wounds can delay wound healing. Herein, we designed a chiral L-phenylalanine-based (LPFEG) supramolecular hydrogel platform that was co-assembled with polydopamine nanoparticles (PDA-NPs). Among them, PDA-NPs can offer photothermal therapy and scavenge free radicals in surgical wounds. LPFEG can create a chiral microenvironment that promotes fibroblast adhesion, proliferation, and new tissue regeneration. Furthermore, with anticancer drug doxorubicin (DOX) loaded into the composite hydrogel, the antitumor effect is considerably boosted. Therefore, the PDA-based chiral supramolecular hydrogel shows high application potential as a postoperative adjuvant in preventing tumor relapse as well as accelerating wound healing after surgery.

Multifunctional carboxymethyl chitosan/oxidized dextran/sodium alginate hydrogels as dressing for hemostasis and closure of infected wounds

Massive bleeding is a great threat to the life safety of patients, which is a challenging clinical problem. Therefore, it is urgent to develop a kind of multifunctional dressing material with hemostatic ability and antibacterial performance to promote wound healing and repair. To resolve this issue, in this study, a carboxymethyl chitosan (CMCS)/sodium alginate (SA)/oxidized dextran (ODE) (CSO) multifunctional hydrogel was developed. The hydrogel could rapidly gel through Schiff base reaction and amide reaction and firmly adhere to the skin at the wound, to realize the fast hemostasis. Importantly, it was verified that the hydrogel could prevent the Staphylococcus aureus-caused wound infection, owing to the antibacterial effect of CMCS and ODE. In addition, the CSO hydrogel had good water retention capacity and was able to mimic the three-dimensional structure of the natural extracellular matrix, thereby promoting wound repair in mice. In vitro whole-blood clotting assay demonstrated that red blood cells could be adhered to the surface of hydrogel, showing good hemostasis in rat liver injury and tail amputation models. Together with the biocompatible feature, CSO hydrogel holds a great application prospect in hemostasis and wound healing.

Antioxidant Silk Fibroin Composite Hydrogel for Rapid Healing of Diabetic Wound.

Wound healing is a complex process requiring multiple biological pathways and chemical responses to be activated and synchronized to recover tissue integrity. In normal physiological circumstances, the epidermal barrier restoration process through new tissue formation is highly efficient. However, increased production of reactive oxygen species (ROS), attack of pathogenic microorganisms, and high glucose level delay the normal healing process in diabetic patients. The successful treatment of diabetic wounds requires efficient strategies to control oxidative stress, promoting angiogenesis, re-epithelialization, and collagen deposition. In this study, a composite hydrogel for rapid wound healing in diabetic condition is developed by the amalgamation of hypolipidemic property of silk fibroin (SF), antioxidant property of melanin, and therapeutic effect of berberine. Studies have revealed that cross-linked mesoporous morphology of hydrogel matrix facilitates slow release of berberine to impart long-term therapeutic effects at wound site. The composite hydrogel formulation is biocompatible, stimulates effective migration of fibroblast cells, and control oxidative stress under in vitro conditions. The hydrogel served as scaffold for tissue re-epithelialization and promotes wound repair in diabetic type I Wistar rat model. This study demonstrates the ability of berberine- loaded SF-melanin composite hydrogel as a potential dressing formulation for wound healing in diabetic conditions.