Promote Wound Repair Research Articles

Multifunctional Ag-Poly(N-isopropylacrylamide/itaconic Acid) Hydrogel Nanocomposites Prepared by Gamma Irradiation for Potential Application as Topical Treatment Dressings.

Today, hydrogel dressings that can protect injury sites and effectively promote healing have become highly desirable in wound management. Therefore, multifunctional silver-poli(N-isopropylacrylamide/itaconic acid) (Ag-P(NiPAAm/IA)) hydrogel nanocomposites were developed for potential application as topical treatment dressings. The radiolytic method, used for the crosslinking of the polymer matrix as well as for the in situ incorporation of silver nanoparticles (AgNPs) into the polymer matrix, enables the preparation of hydrogel nanocomposites without introducing harmful and toxic agents. Moreover, materials produced using γ-irradiation are simultaneously sterilized, thus fulfilling one of the basic requirements regarding their potential biomedical applications. The NiPAAm/IA ratio and the presence of AgNPs influenced the microstructural parameters of the investigated systems. Increasing the IA content leads to the formation of a more porous polymer matrix with larger pores, while the incorporated AgNPs act as additional junction points, decreasing the porosity and pore size of the resulting nanocomposite hydrogels. Swelling studies showed that most investigated systems uptake the fluids from their surroundings by non-Fick diffusion. Further, the Ag+ ion release, antibacterial activity, and cytotoxicity of Ag-P(NiPAAm/IA) hydrogel nanocomposites were examined to evaluate their biomedical potential. All hydrogel nanocomposites showed an initial burst release of Ag+ ions (useful in preventing bacteria adherence and biofilm formation), followed by a slower release of the same (ensuring sterility for longer use). An antibacterial activity test against Escherichia coli and Staphylococcus aureus showed that Ag-P(NiPAAm/IA) hydrogel nanocomposites, with silver concentrations around 10 ± 1 ppm, successfully prevent bacterial growth. Finally, it was shown that the investigated hydrogel nanocomposites do not exhibit a cytotoxic effect on human keratinocyte HaCaT cells. Therefore, these multifunctional hydrogel nanocomposites may promote wound repair and show promising potential for application as functional wound dressing.

Platelet-rich plasma promotes wound repair in diabetic foot ulcer mice via the VEGFA/VEGFR2/ERK pathway

Diabetic foot ulcers (DFUs) are a severe microvascular complication. Platelet-rich plasma (PRP) pitches in DFU treatment. This study explored the mechanism of PRP facilitating wound repair in DFU mice via vascular endothelial growth factor A (VEGFA)/VEGF receptor 2 (VEGFR2)/extracellular signal-regulated kinase (ERK) pathway. The DFU mouse model was established, with wound skin injected with PRP, followed by the detections of wound area, histopathological changes, and CD31-positive cells. IL-6/TNF-α/VEGFA/VEGFR2/p-VEGFR2/(ERK1/2)/(p-ERK1/2) levels in wound tissue homogenates were assessed. VEGFA-VEGFR2 interaction was evaluated. PRP-treated DFU mice were simultaneously treated with fruquintinib/PD98059. PRP reduced wound area, IL-6 and TNF-α levels, elevated epidermal dermal thickness, CD31-positive cell number, and aligned tissue structure, which were mitigated by fruquintinib/PD98059. PRP promoted VEGFR2 phosphorylation. PRP and fruquintinib/PD98059 abated p-VEGFR2/VEGFR2 or p-ERK1/2/ERK1/2 levels in DFU mice. PRP activated the ERK pathway through VEGFA/VEGFR2. Collectively, PRP promoted VEGFR2 phosphorylation and activated the ERK pathway, thereby facilitating wound repair in DFU mice.

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.

Graphene-Based Wound Dressings for Wound Healing: Mechanism, Technical Analysis, and Application Status.

The development of novel wound dressings is critical in medical care. Graphene and its derivatives possess excellent biomedical properties, making them highly suitable for various applications in medical dressings. This review provides a comprehensive technical analysis and the current application status of graphene-based medical dressings. Initially, we discuss the chemical structure and the fabrication method of graphene and its derivatives. We then provide a detailed summary of the mechanisms by which graphene materials promote wound repair across the four stages of wound healing. Subsequently, we categorize the types of graphene-based wound dressings and analyze corresponding characteristics. Finally, we analyze the challenges encountered at present and propose solutions regarding future development trends. This paper aims to serve as a reference for further research in skin tissue engineering and the development of innovative graphene-based medical dressings.

C. elegans epicuticlins define specific compartments in the apical extracellular matrix and function in wound repair.

The apical extracellular matrix (aECM) of external epithelia often contains lipid-rich outer layers that contribute to permeability barrier function. The external aECM of nematodes is known as the cuticle and contains an external lipid-rich layer - the epicuticle. Epicuticlins are a family of tandem repeat cuticle proteins of unknown function. Here, we analyze the localization and function of the three C. elegans epicuticlins (EPIC proteins). EPIC-1 and EPIC-2 localize to the surface of the cuticle near the outer lipid layer, as well as to interfacial cuticles and adult-specific struts. EPIC-3 is expressed in dauer larvae and localizes to interfacial aECM in the buccal cavity. Skin wounding in the adult induces epic-3 expression, and EPIC proteins localize to wound sites. Null mutants lacking EPIC proteins are viable with reduced permeability barrier function and normal epicuticle lipid mobility. Loss of function in EPIC genes modifies the skin blistering phenotypes of Bli mutants and reduces survival after skin wounding. Our results suggest EPIC proteins define specific cortical compartments of the aECM and promote wound repair.

Dual-Responsive Antibacterial Hydrogel Patch for Chronic-Infected Wound Healing.

Bacterial infections in chronic wounds, such as bedsores and diabetic ulcers, present significant healthcare challenges. Excessive antibiotic use leads to drug resistance and lacks precision for targeted wound treatment. Our study introduces an innovative solution: a near-infrared (NIR) and pH dual-responsive hydrogel patch incorporating regenerated silk fibroin (RSF) and molybdenum dioxide (MoO2) nanoparticles (NPs), offering enhanced mechanical properties, precise drug release, and superior antibacterial efficacy. The dual-responsive hydrogel patch allows for precise control over antibiotic release triggered by NIR light and pH fluctuations, enabling tailored treatment for infected wounds. First, the pH-responsive characteristic matches the alkaline environment of the infected wound, ensuring on-demand antibiotic release. Second, NIR exposure accelerates antibiotic release, enhancing wound healing and providing additional antibacterial effects. Additionally, the patch further blocks bacterial infection, promotes wound repair, and degrades in sync with the healing process, further bolstering the efficacy against wound infections.

Trehalose Prevents IL-4/IL-13–Induced Skin Barrier Impairment by Suppressing IL-33 Expression and Increasing NRF2 Activation in Human Keratinocytes In Vitro

Skin barrier dysfunction initiates or deteriorates various cutaneous problems, such as atopic dermatitis (AD). At high concentrations, the nonreducing disaccharide α-d-glucopyranosyl α-d-glucopyranoside (trehalose) induces a transient senescence-like state in fibroblasts and promotes wound repair. Here, we investigated the effect of trehalose on normal human keratinocytes (KCs) and demonstrated its specific role in the skin barrier. RNA-seq analysis revealed that trehalose regulates the expression of many skin-barrier-associated genes. T helper 2 (Th2) cytokines interleukin (IL)-4/IL-13 were observed to downregulate several differentiation markers (FLG, LOR, K1, and K10) and epidermal antimicrobial proteins in monolayer-cultured KCs and living skin equivalents (LSE), and impaired skin barrier function in LSE, all of which were significantly upregulated or restored by trehalose. Trehalose inhibited IL-33 expression and reduced nuclear IL-33 levels by activating MEK5-extracellular signal-regulated kinase 5 (ERK5) and suppressing MEK1/2-ERK pathway. It also increased nuclear factor erythroid 2-related factor 2 (Nrf2) activation to trigger antioxidant enzyme production via c-Jun N-terminal kinase (JNK), thus, neutralizing IL-4/IL-13-mediated oxidative stress. Trehalose prevented IL-4/IL-13-mediated signal transducer and activator of transcription (STAT)3/STAT6 activation and restored IL-4/IL-13-suppressed skin barrier molecules via IL-33 downregulation and Nrf2 activation. This study demonstrated that trehalose may play a role in skin barrier repair in AD.

Synthesis and characterization of a novel dual sensitive iron nanoparticles incorporated Schiff base composite hydrogel for diabetic wound healing therapy

Chronic wounds in diabetic patients deteriorate into multiple infections. A multifunctional transdermal material with high self-healing ability, remodeling capability, antibacterial and radicle scavenging activity, and an excellent multi-sensitive carrier was needed to promote wound healing. For that, Oxidized Cellulose (OC) and gelatin (GLN) are selected to construct a dual drug-loaded Schiff base hydrogel with iron nanoparticle (IONPS) incorporation for the controlled and sustained release of Insulin (INS) and Metfomin (MET), which synergistically promote wound repair. The INS/MET-IONPS-OC/GLN hydrogel drug payload was characterized using FT-IR, XRD, DLS, ZETA, TG, FE-SEM, TEM, and VSM analysis. The high drug loading and encapsulation efficiency were 93.20 % and 98.8 % for INS and 90.2 % and 95.1 % for MET, respectively. The temperature-sensitive drug release (92.0 % of INS and 90.0 % of MET) percentage is much better than the pH-sensitive drug release (83.5 % of INS and 80.2 % of MET). Above 90.0 % viability in MTT and apoptosis assay reveals the nontoxic nature of the INS/MET-IONPS-OC/GLN towards L929 normal cell lines. The zone of inhibition value of 12 and 15 mm in gram-negative bacteria reveals the anti-bacterial effect. The antioxidant activity of the carrier shields the cells against reactive oxygen species promotes healing rate ensures by DPPH assay.The cell proliferation and angiogenesis were confirmed by scratch assay on L929 cell lines in diabetic and non-diabetic conditions, showing the healing ability of the INS/MET-IONPS-OC/GLN hydrogel.

The Effect of Polynucleotide‐Hyaluronic Acid Hydrogel in the Recovery After Mechanical Skin Barrier Disruption

ABSTRACTBackgroundThe epidermal barrier acts as a defense against external agents as well as helps to maintain body homeostasis. Polynucleotides (PN), exogenous DNA fragments, promote wound repair through their stimulatory and anti‐inflammatory effects. Recent findings indicate a synergistic effect of PN and hyaluronic acid (HA) combinations in regulating inflammation and promoting cell proliferation. This study aims to elucidate the effects of PN and HA on repairing the epidermal barrier following its disruption by tape stripping (TS) in a mouse model.Materials and MethodsAfter disrupting the epidermal barrier using TS, a formulation containing PN (14 mg/mL) and HA (6 mg/mL) was applied. Trans‐epidermal water loss (TEWL) was measured at 0, 3, 6, 24, 48, and 72 h. Mice were euthanized after the final application at 72 h, and tissue samples were analyzed for epidermal/dermal thickness, neutrophil infiltration, and filaggrin expression.ResultsWe observed a significant reduction in TEWL in the PN+HA group compared to that in the control group (20.8 ± 0.5 vs. 43.7 ± 0.5 g/m2h at 72 h, p < 0.05), indicating an improvement in barrier function. Histological evaluation showed decreased epidermal and dermal thickening in the PN+HA group compared to that in the control group (epidermal: 29.4 ± 2.2 vs. 57.9 ± 3.5 μm; dermal: 464.8 ± 25.9 vs. 825.9 ± 44.8 μm, both p < 0.05). Additionally, neutrophil infiltration in the dermis was significantly reduced, and filaggrin protein levels were significantly higher in the PN+HA group compared to those in the control group (4.8 ± 0.4 vs. 21.1 ± 3.3 for neutrophils; 0.84 ± 0.04 vs. 0.42 ± 0.03 for filaggrin, both p < 0.05).ConclusionThese results suggest that PN+HA may be an effective therapeutic strategy for repairing skin barrier damage.

Nanoarchitectonics of in Situ Antibiotic-Releasing Acicular Nanozymes for Targeting and Inducing Cuproptosis-like Death to Eliminate Drug-Resistant Bacteria.

A series of progress has been made in the field of antimicrobial use of nanozymes due to their superior stability and decreased susceptibility to drug resistance. However, catalytically generated reactive oxygen species (ROS) are insufficient for coping with multidrug-resistant organisms (MDROs) in complex wound environments due to their low targeting ability and insufficient catalytic activity. To address this problem, chemically stable copper-gallic acid-vancomycin (CuGA-VAN) nanoneedles were successfully constructed by a simple approach for targeting bacteria; these nanoneedles exhibit OXD-like and GSH-px-like dual enzyme activities to produce ROS and induce bacterial cuproptosis-like death, thereby eliminating MDRO infections. The results of in vitro experiments showed that the free carboxylic acid of GA could react with the free ammonia of teichoic acid in the methicillin-resistant Staphylococcus aureus (MRSA) cell wall skeleton. Thus, CuGA-VAN nanoneedles can rapidly "capture" MRSA in liquid environments, releasing ROS, VAN and Cu2+ on bacterial surfaces to break down the MRSA barrier, destroying the biofilm. In addition, CuGA-VAN effectively promoted wound repair cell proliferation and angiogenesis to facilitate wound healing while ensuring biosafety. According to transcriptome sequencing, highly internalized Cu2+ causes copper overload toxicity; downregulates genes related to the bacterial glyoxylate cycle, tricarboxylic acid cycle, and oxidative respiratory chain; and induces lipid peroxidation in the cytoplasm, leading to bacterial cuproptosis-like death. In this study, CuGA-VAN was cleverly designed to trigger a cascade reaction of targeting, drug release, ROS-catalyzed antibacterial activity and cuproptosis-like death. This provides an innovative idea for multidrug-resistant infections.

Gelatin/Dopamine/Zinc-Doped Ceria/Curcumin nanocomposite hydrogels for repair of chronic refractory wounds

Chronic wound healing is a common clinical challenge, characterized by bacterial infection, protracted inflammatory response, oxidative stress, and insufficient neovascularization. Nanozymes have emerged as a promising solution for treating skin wounds due to their antioxidant, antibacterial, and angiogenic properties. In recent years, combining nanozymes with hydrogels to jointly promote wound healing has attracted increasing research interest. However, most of the current nanocomposite hydrogels are still not effective in simultaneously controlling inflammatory, oxidative stress and bacterial invasion in wound healing. Improving the therapeutic functional diversity and efficacy of nanocomposite hydrogels remains a problem that needs to be addressed. In this study, we prepared nanocomposite hydrogels (GelMD-Cur@ZHMCe) by combining methylacrylated gelatin modified with dopamine (GelMD) with Zinc-doped hollow mesoporous cerium oxide nanoparticles loaded with curcumin (Cur@ZHMCe). The resulting hydrogels exhibited excellent water absorption, adhesion, and biocompatibility. In vitro and in vivo studies have demonstrated that GelMD-Cur@ZHMCe has excellent antioxidant, antibacterial, anti-inflammatory and vasculature-promoting properties, which enable it to rapidly promote wound repair. The wound healing rate of the rat total skin defect infection model treated with GelMD-Cur@ZHMCe reached 98.5±4.9 % after 14 days of treatment. It was demonstrated that this multifunctional nanocomposite hydrogel provides a promising therapeutic strategy for skin repair.

Critical role of thrombospondin-1 in promoting intestinal mucosal wound repair.

Thrombospondin-1 (TSP1) is a matricellular protein associated with the regulation of cell migration through direct binding interactions with integrin proteins and by associating with other receptors known to regulate integrin function, including CD47 and CD36. We previously demonstrated that deletion of an epithelial TSP1 receptor, CD47, attenuates epithelial wound repair following intestinal mucosal injury. However, the mechanisms by which TSP1 contributes to intestinal mucosal repair remain poorly understood. Our results show upregulated TSP1 expression in colonic mucosal wounds and impaired intestinal mucosal wound healing in vivo upon intestinal epithelium-specific loss of TSP1 (VillinCre/+ Thbs1fl/fl or Thbs1ΔIEC mice). We report that exposure to exogenous TSP1 enhanced migration of intestinal epithelial cells in a CD47- and TGF-β1-dependent manner and that deficiency of TSP1 in primary murine colonic epithelial cells resulted in impaired wound healing. Mechanistically, TSP1 modulated epithelial actin cytoskeletal dynamics through suppression of RhoA activity, activation of Rho family small GTPase (Rac1), and changes in filamentous-actin bundling. Overall, TSP1 was found to regulate intestinal mucosal wound healing via CD47 and TGF-β1, coordinate integrin-containing cell-matrix adhesion dynamics, and remodel the actin cytoskeleton in migrating epithelial cells to enhance cell motility and promote wound repair.

Pyroptosis does damage control.

Secreted factors from pyroptotic cells can promote wound repair.

VR23 and Bisdemethoxycurcumin Enhanced Nanofiber Niche with Durable Bidirectional Functions for Promoting Wound Repair and Inhibiting Scar Formation.

Chronic wounds pose a significant clinical challenge worldwide, which is characterized by impaired tissue regeneration and excessive scar formation due to over-repair. Most studies have focused on developing wound repair materials that either facilitate the healing process or control hyperplastic scars caused by over-repair, respectively. However, there are limited reports on wound materials that can both promote wound healing and prevent scar hyperplasia at the same time. In this study, VR23-loaded dendritic mesoporous bioglass nanoparticles (dMBG) are synthesized and electrospun in poly(ester-curcumin-urethane)urea (PECUU) random composite nanofibers (PCVM) through the synergistic effects of physical adsorption, hydrogen bond, and electrospinning. The physicochemical characterization reveals that PCVM presented matched mechanical properties, suitable porosity, and wettability, and enabled sustained and temporal release of VR23 and BDC with the degradation of PCVM. In vitro experiments demonstrated that PCVM can modulate the functions and polarization of macrophages under an inflammatory environment, and possess effective anti-scarring potential and reliable cytocompatibility. Animal studies further confirmed that PCVM can efficiently promote re-epithelialization and angiogenesis and reduce excessive inflammation, thereby remarkably accelerating wound healing while preventing potential scarring. These findings suggest that the prepared PCVM holds promise as a bidirectional regulatory dressing for effectively promoting scar-free healing of chronic wounds.

Injectable hydrogel with doxorubicin-loaded ZIF-8 nanoparticles for tumor postoperative treatments and wound repair

The need for tumor postoperative treatments aimed at recurrence prevention and tissue regeneration have raised wide considerations in the context of the design and functionalization of implants. Herein, an injectable hydrogel system encapsulated with anti-tumor, anti-oxidant dual functional nanoparticles has been developed in order to prevent tumor relapse after surgery and promote wound repair. The utilization of biocompatible gelatin methacryloyl (GelMA) was geared towards localized therapeutic intervention. Zeolitic imidazolate framework-8@ceric oxide (ZIF-8@CeO2, ZC) nanoparticles (NPs) were purposefully devised for their proficiency as reactive oxygen species (ROS) scavengers. Furthermore, injectable GelMA hydrogels loaded with ZC NPs carrying doxorubicin (ZC-DOX@GEL) were tailored as multifunctional postoperative implants, ensuring the efficacious eradication of residual tumor cells and alleviation of oxidative stress. In vitro and in vivo experiments were conducted to substantiate the efficacy in cancer cell elimination and the prevention of tumor recurrence through the synergistic chemotherapy approach employed with ZC-DOX@GEL. The acceleration of tissue regeneration and in vitro ROS scavenging attributes of ZC@GEL were corroborated using rat models of wound healing. The results underscore the potential of the multifaceted hydrogels presented herein for their promising application in tumor postoperative treatments.

A new mechanism in negative pressure wound therapy: interleukin-17 alters chromatin accessibility profiling.

Negative pressure wound therapy (NPWT) is extensively used in clinical settings to enhance the healing of wounds. Despite its widespread use, the molecular mechanisms driving the efficacy of NPWT have not been fully elucidated. In this study, skin wound-healing models were established, with administration of NPWT. Vimentin, collagen I, and MMP9 of skin tissues were detected by immunofluorescence (IF). Gene expression analysis of skin wound tissues was performed by RNA-sequencing (RNA-seq). Protein expression was assayed by a Western blotting or IF assay, and mRNA levels were quantified by quantitative PCR. Chromatin accessibility profiles of fibroblasts following NPWT or IL-17 exposure were analyzed by ATAC-seq. In rat wound-healing models, NPWT promoted wound repair by promoting reepithelialization, extracellular matrix (ECM) synthesis, and proliferation, which mainly occurred in the early stage of wound healing. These differentially expressed genes (DEGs) in NPWT wounds versus control wounds were enriched in the IL-17 signaling pathway. IL-17 was identified as an upregulated factor following NPWT in skin wounds. Moreover, the IL-17 inhibitor secukinumab (SEC) could abolish the promoting effect of NPWT on wound healing. Importantly, chromatin accessibility profiles were altered following NPWT and IL-17 stimulation in skin fibroblasts. Our findings suggest that NPWT upregulates IL-17 to promote wound healing by altering chromatin accessibility, which is a novel mechanism for NPWT's efficacy in wound healing.NEW & NOTEWORTHY To our knowledge, this is the first report of the efficacy of negative pressure wound therapy (NPWT) in promoting wound healing via IL-17. Moreover, NPWT and IL-17 can alter chromatin accessibility. Our study identifies a novel mechanism for NPWT's efficacy in wound healing.

Hyaluronic acid-based injectable formulation developed to mitigate metastasis and radiation-induced skin fibrosis in breast cancer treatment

The standard treatment for early-stage breast cancer involves breast-conserving surgery followed by adjuvant radiotherapy. However, approximately 20 % of patients experience distant metastasis, and adjuvant radiotherapy often leads to radiation-induced skin fibrosis (RISF). In this study, we develop an on-site injectable formulation composed of selenocystamine (SeCA) and hyaluronic acid (HyA), referred to as SeCA cross-linked HyA (SCH) agent, and investigate its potential to mitigate metastasis and prevent RISF associated with breast cancer therapy. SCH agents are synthesized using the nanoprecipitation method to modulate cell-cell tight junctions and tissue inflammation. The toxicity assessments reveal that SCH agents with a higher Se content (Se payload 17.4 μg/mL) are well tolerated by L929 cells compared to SeCA (Se payload 3.2 μg/mL). In vitro, SCH agents significantly enhance cell–cell tight junctions and effectively mitigate migration and invasion of breast cancer cells (4T1). In vivo, SCH agents mitigate distant lung metastasis. Furthermore, in animal models, SCH agents reduce RISF and promote wound repair. These findings highlight the potential of SCH agents as a novel therapeutic formulation for effectively mitigating metastasis and reducing RISF. This holds great promise for improving clinical outcomes in breast cancer patients undergoing adjuvant radiotherapy.

Multifunctional polyvinyl alcohol/gallic acid functionalized chitosan hydrogels prepared by freeze-thaw method for potential application as wound dressings

The design of multifunctional hydrogel dressings to effectively promote wound healing is highly desirable in clinical trauma and surgery. Inspired by excellent mechanical properties of polyvinyl alcohol (PVA) and strong adhesion of polyphenols, gallic acid was grafted onto chitosan molecular chain (CS-GA) by free radical polymerization in this study, and PVA/CS-GA hydrogels were successfully prepared by repeated freeze-thaw method, without introducing toxic crosslinking agents. The prepared PVA/CS-GA hydrogels could adhere to various substrates, which confirmed excellent universal adhesion properties. The red blood cells adhesion ratio was 67.1%, indicating its potential for promoting wound coagulation. Meanwhile, the mechanical strength of PVA/CS-GA hydrogel was significantly enhanced, exhibiting approximately twice tensile strength and failure stretch compared with PVA hydrogel. Furthermore, attributing to GA molecule, PVA/CS-GA hydrogels not only showed favorable antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), but also could scavenge free radicals, showing effective antioxidant activity. The hydrogels also had good biocompatibility, met the basic requirements of biomedical materials and may promote wound repair. It should be noted that the content of GA had significant impact on cytotoxicity. Therefore, multifunctional PVA/CS-GA hydrogels with excellent mechanical, adhesion, antioxidant, antibacterial and biocompatible properties show promising potential applications in the biomedicine field, especially as functional wound dressings.

Allogeneic platelet-rich plasma inhibits ferroptosis in promoting wound repair of type 2 diabetic ulcers

Increasing evidence has revealed the emerging role of ferroptosis in the pathophysiology of type 2 diabetes mellitus (T2DM) and its complications. Platelet-rich plasma (PRP) has been demonstrated to facilitate the healing of T2DM ulcers. However, the mechanism by which PRP repairs T2DM ulcers remains unclear. Here, we sought to investigate the interaction between PRP and ferroptosis in repairing T2DM ulcers. The results showed that the cellular activity, proliferation, and migration of fibroblasts were down-regulated, and the cellular activity and normal function of vascular endothelial cells were impaired in the high glucose environment or under RSL3 conditions (a GSH peroxidase 4 inhibitor and ferroptosis inducer). Additionally, both cells experienced over-activation of multiple forms of reactive oxygen species (ROS) and lipid peroxidation. In the T2DM rat model, we observed a decreased rate of ulcer wound healing, impaired proliferative capacity, diminished vascular regeneration, and marked inflammation and hyperfibrosis. More importantly, there was typical damage to mitochondria, increased levels of iron ions, and consistent alterations in protein expression of ferroptosis-related factors. These factors include cyclooxygenase-2 (COX2), glutathione peroxidase 4 (GPX4), transferrin receptor (TFRC), and Solute Carrier Family 7 Member 11 (SLC7A11), among others. Due to the strong association between ferroptosis and T2DM ulcers, the use of allogeneic platelet-rich plasma (Al-PRP) exhibited physiological effects similar to those of the ferroptosis inhibitor Ferrostatin-1 (Fer-1). In vivo experiments, both drugs inhibited a range of impediments to wound healing caused by T2DM and ameliorated the adverse effects associated with ferroptosis. Moreover, Al-PRP attenuated the impairment of normal cellular function, activation of ROS and lipid peroxidation induced by high glucose or RSL3. These results suggested that ferroptosis was involved in the development of T2DM ulcers, which could be treated with Al-PRP by inhibiting ferroptosis, and inhibition of ferroptosis may be a suitable treatment strategy for T2DM ulcers.

Thiolation-Based Protein-Protein Hydrogels for Improved Wound Healing.

The limitations of protein-based hydrogels, including their insufficient mechanical properties and restricted biological functions, arise from the highly specific functions of proteins as natural building blocks. A potential solution to overcome these shortcomings is the development of protein-protein hydrogels, which integrate structural and functional proteins. In this study, a protein-protein hydrogel formed by crosslinking bovine serum albumin (BSA) and a genetically engineered intrinsically disordered collagen-like protein (CLP) through Ag─S bonding is introduced. The approach involves thiolating lysine residues of BSA and crosslinking CLP with Ag+ ions, utilizing thiolation of BSA and the free-cysteines of CLP. The resulting protein-protein hydrogels exhibit exceptional properties, including notable plasticity, inherent self-healing capabilities, and gel-sol transition in response to redox conditions. In comparison to standalone BSA hydrogels, these protein-protein hydrogels demonstrate enhanced cellular viability, and improved cellular migration. In vivo experiments provide conclusive evidence of accelerated wound healing, observed not only in murine models with streptozotocin (Step)-induced diabetes but also in zebrafish models subjected to UV-burn injuries. Detailed mechanistic insights, combined with assessments of proinflammatory cytokines and the expression of epidermal differentiation-related proteins, robustly validate the protein-protein hydrogel's effectiveness in promoting wound repair.