Facilitate Wound Healing Research Articles

Scanning electron microscopy-based quantification of keratin and hyaluronic acid microstructure in electrospun scaffolds

BackgroundThe extracellular matrix (ECM) structural deficiencies in chronic wounds prevent the wounds from healing through natural physiological processes. Electrospun biocompatible polymers offer a platform to produce microstructure wound dressing materials that mimic the ECM containing various bioactives to address the deficiencies in the chronic wound healing process. Quantitative characterization of the electrospun fiber microstructure could provide valuable information on using fiber constructs to facilitate wound healing. This work employed a validated image analysis tool to quantitatively explain various parameters for the microstructure of six electrospun fiber constructs, D1{Polycaprolactone (PCL), Polyvinyl alcohol (PVA), Keratin}, D2{PCL, PVA, keratin, Co-enzyme Q10 (CoQ10)}, D3 (PCL, PVA, keratin, mupirocin), D4 (PCL, PVA, keratin, CoQ10, mupirocin, valsartan), D5 {PVA, Hyaluronic acid (HA)}, and D6 (PVA), using scanning electron microscopy imaging modality.ResultsThe fiber intersection density (FID) parameter was quantified in the formulations, e.g., 0.272% for D5 and 0.416% for D4. Orientation histograms for D1 and D6 are characteristic of isotropic materials, while orientations for D2 and D3 indicate anisotropy with 2 preferred orientations in each formulation. D4 and D5 present orientations characteristic of transversely isotropic materials. The tortuosity for D2 and D4 indicates almost straight fiber segments, in contrast with undulated fiber segments in all other formulations. Furthermore, the mean fiber diameter was quantified, e.g., 1.414 and 1.630 mm for D3 and D4, respectively.ConclusionCo-electrospun PVA/PCL microfibers offer great potential for controlled delivery of bioactives needed to accelerate the healing of chronic wounds. This image-based analysis technology quantitatively characterized different formulations of electrospun fiber scaffolds. This analysis sets the stage for future study that utilizes microstructural information in finite element biomechanical modeling, to investigate possible influence of structure-based mechanical factors on the ECM restorative potential of wound dressings. Adjustment of electrospinning conditions could produce fabricated constructs like the native ECM structural components with a functional role in wound healing.

Hypoxic microenvironment promotes diabetic wound healing by polarizing macrophages to the M2 phenotype in vivo.

In diabetic wounds, M2 polarization of macrophages regulates the transition from an inflammatory phase to a proliferative phase. Prior investigations have demonstrated the potential of deferoxamine (DFO) in creating a localized hypoxic microenvironment, which could stimulate angiogenesis by promoting vascular endothelial growth factor (VEGF) secretion in diabetic wound healing. Nevertheless, there is still no clear information on whether this chemically induced hypoxic microenvironment modulates macrophage polarization to promote diabetic wound healing. The 18 diabetic mice were randomly divided into three groups: a control group (n = 6), a 100µM DFO group (n = 6), and a 200µM DFO group (n = 6). Subsequently, a full-thickness wound with a diameter of 1.00cm was created on the dorsal region of the diabetic mice. Observe wound closure regularly during treatment. At the end of the observation, tissue specimens were collected for a series of experiments and analyses, including hematoxylin and eosin (H&E), Masson, immunofluorescent, and immunohistochemical staining. The role and mechanism of DFO in regulating macrophage polarization were studied using RAW264.7 cells. In comparison to the control group, the administration of DFO notably facilitates wound healing in diabetic mice. In diabetic wounds, DFO increases blood supply by upregulating VEGF, which promotes angiogenesis. Additionally, The expression of HSP70 and CD206 were also upregulated by DFO in both vivo and in vitro, while iNOS expression was downregulated. Additionally, knk437 inhibited the expression of HSP70 in RAW264.7 cells, resulting in a reduction of M2 polarization and an increase in M1 polarization. The induction of a hypoxic microenvironment by DFO has been found to exert a substantial influence on the process of diabetic wound healing. DFO treatment enhances the capacity of diabetic wounds to stimulate angiogenesis and modulate macrophage polarization that may be associated with HSP70 expression, thereby expediting the transition of these wounds from an inflammatory to a proliferative state.

Concanavalin-conjugated zinc-metal-organic framework drug for pH-controlled and targeted therapy of wound bacterial infection

Wounds are prone to infection which may be fatal to the life of the patient. The use of antibiotics is essential for managing bacterial infections in wounds, but the long-term use of high doses of antibiotics may lead to bacterial drug resistance and even to creation of superbacteria. Therefore, the development of targeted antimicrobial treatment strategies and the reduction in antibiotic usage are of utmost urgency. In this study, a multifunctional nanodrug delivery system (Cef-rhEGF@ZIF-8@ConA) for the treatment of bacteriostatic infection was synthesized through self-assembly of Zn2+, cefradine (Cef) and recombinant human epidermal growth factor (rhEGF), then conjugated with concanavalin (ConA), which undergoes pH-responsive degradation to release the drugs. First, ConA can specifically combine with bacteria and inhibit the rapid release of Zn2+ ions, thus achieving a long-acting antibacterial effect. Cef exerts its antibacterial effect by inhibiting the synthesis of bacterial membrane proteins. Finally, Zn2+ ions released from the Zn-metal-organic framework (MOF) demonstrate bacteriostatic properties by enhancing the permeability of the bacterial cell membrane. Furthermore, rhEGF upregulates angiogenesis-associated genes, thereby promoting angiogenesis, re-epithelialization and wound healing processes. The results showed that Cef-rhEGF@ZIF-8@ConA has good biocompatibility, with antibacterial efficacy against Staphylococcus aureus and Escherichia coli of 99.61 % and 99.75 %, respectively. These nanomaterials can inhibit the release of inflammatory cytokines and promote the release of anti-inflammatory cytokines, while also stimulating the proliferation of fibroblasts to facilitate wound healing. Taken together, the Cef-rhEGF@ZIF-8@ConA nanosystem is an excellent candidate in clinical therapeutics for bacteriostatic infection and wound healing.

The Core-Shell Microneedle with Probiotic Extracellular Vesicles for Infected Wound Healing and Microbial Homeostasis Restoration.

Wound healing is a dynamic process involving the timely transition of organized phases. However, infected wounds often experience prolonged inflammation due to microbial overload. Thus, addressing the viable treatment needs across different healing stages is a critical challenge in wound management. Herein, a novel core-shell microneedle (CSMN) patch is designed for the sequential delivery of tannic acid-magnesium (TA-Mg) complexes and extracellular vesicles from Lactobacillus druckerii (LDEVs). Upon application to infected sites, CSMN@TA-Mg/LDEV releases TA-Mg first to counteract pathogenic overload and reduce reactive oxygen species (ROS), aiding the transition to proliferative phase. Subsequently, the sustained release of LDEVs enhances the activities of keratinocytes and fibroblasts, promotes vascularization, and modulates the collagen deposition. Notably, dynamic track of microbial composition demonstrates that CSMN@TA-Mg/LDEV can both inhibit the aggressive pathogen and increase the microbial diversity at wound sites. Functional analysis further highlights the potential of CSMN@TA-Mg/LDEV in facilitating wound healing and skin barrier restoration. Moreover, it is confirmed that CSMN@TA-Mg/LDEV can accelerate wound closure and improve post-recovery skin quality in the murineinfected wound. Conclusively, this innovative CSMN patch offers a rapid and high-quality alternative treatment for infected wounds and emphasizes the significance of microbial homeostasis.

Mechanism of action of montmorillonite powder on injury and repair factors in Stage II pressure ulcers in model mice.

This study aims to elucidate the therapeutic effects and underlying mechanisms of montmorillonite powder on wound healing in mice with Stage II pressure ulcers, thereby providing a robust foundation for its clinical application in the treatment of such ulcers. Sixty 8-week-old specific pathogen-free male BALB/c mice were randomly allocated into three groups: a model group (where Stage II pressure ulcers were induced using the magnet pressure method and the wounds were dressed with gauze soaked in 0.9% sodium chloride solution), a treatment group (where, following the induction of Stage II pressure ulcer models, wounds were uniformly treated with montmorillonite powder), and a control group (where magnets were placed in the same location without exerting magnetic pressure). Skin histopathology was assessed via light microscopy. Wound healing progress over various intervals was quantified utilizing Image-Pro Plus software. Histopathological alterations in the wounds were examined through hematoxylin and eosin (H&E) staining. The expression of growth factor proteins within the wound tissue was analyzed using the streptavidin-peroxidase method. Furthermore, the levels of vascular endothelial growth factor (VEGF), collagen types I and III (COL-I, COL-III) proteins were quantified via Western blotting, serum concentrations of inflammatory mediators in mice were determined by enzyme-linked immunosorbent assay, and the levels of oxidative stress markers in wound tissues were measured using UV-visible spectrophotometry. The treatment group exhibited significantly reduced serum levels of interleukin-1β, interleukin-6, and tumor necrosis factor-alpha, and elevated levels of interleukin-4 compared to the model group (p<0.05). Additionally, the expression of transforming growth factor-beta1, basic fibroblast growth factor, epidermal growth factor, VEGF, COL-I, and COL-III proteins in wound tissues was significantly higher in the treatment group than in the model group (p<0.05). Levels of superoxide dismutase and glutathione peroxidase in wound tissues were higher, and levels of malondialdehyde were lower in the treatment group compared to the model group (p<0.05). Montmorillonite powder facilitates wound healing and augments the healing rate of Stage II pressure ulcers in model mice. Its mechanism of action is likely associated with mitigating wound inflammation, reducing oxidative stress damage, promoting angiogenesis, and enhancing the synthesis of growth factors and collagen.

Plant-Derived Chinese Herbal Hydrogel Microneedle Patches for Wound Healing.

Several natural Chinese herbal medicines have demonstrated considerable potential in facilitating wound healing, while the primary concern remains centered around optimizing formulation and structure to maximize their efficacy. To address this, a natural microneedles drug delivery system is proposed that harnesses gelatinized starch and key Chinese herbal ingredients-aloe vera and berberine. After gelatinized and aged in a well-designed mold, the starch-based microneedles are fabricated with suitable mechanical strength to load components. The resulting Chinese herbal hydrogel microneedles, enriched with integrated berberine and aloe, exhibit antibacterial, anti-inflammatory, and fibroblast growth-promoting properties, thereby facilitating wound healing in the whole process. In vivo experimental results underscore the notable achievements of the microneedles in early-stage antibacterial effects and subsequent tissue reconstruction, contributing significantly to the overall wound healing process. These results emphasize the advantageous combination of traditional Chinese medicine with microneedles, presenting a novel strategy for wound repair and opening new avenues for the application of traditional Chinese medicine.

The Role of Hydrogel Biomaterials in the Intervention of Wound Healing and Skin Regeneration via Exosomes: A Systematic Review and Meta-Analysis of Preclinical Animal Studies.

Significance: The combination of hydrogel biomaterials with exosomes to facilitate wound healing and skin regeneration is a promising approach. Recent Advances: Recent preclinical animal studies have focused on investigating the efficacy of hydrogel-based delivery systems for exosomes in promoting wound healing and skin regeneration. Critical Issues: Despite encouraging results, critical issues remain unresolved, such as optimizing hydrogel properties to enhance the efficacy of combined therapy with exosomes for wound and bridging the translational gap between preclinical and clinical applications. Future Directions: Future research endeavors should concentrate on refining hydrogel design to enhance exosome delivery efficacy, conducting rigorous clinical trials to assess the safety and efficacy of exosome-loaded hydrogels in human wound healing and skin regeneration, and exploring innovative strategies to maximize therapeutic outcomes.

Nitric oxide-based treatments improve wound healing associated with diabetes mellitus.

Non-healing wounds are long-term complications of diabetes mellitus (DM) that increase mortality risk and amputation-related disability and decrease the quality of life. Nitric oxide (NO·)-based treatments (i.e., use of both systemic and topical NO· donors, NO· precursors, and NO· inducers) have received more attention as complementary approaches in treatments of DM wounds. Here, we aimed to highlight the potential benefits of NO·-based treatments on DM wounds through a literature review of experimental and clinical evidence. Various topical NO·-based treatments have been used. In rodents, topical NO·-based therapy facilitates wound healing, manifested as an increased healing rate and a decreased half-closure time. The wound healing effect of NO·-based treatments is attributed to increasing local blood flow, angiogenesis induction, collagen synthesis and deposition, re-epithelization, anti-inflammatory and anti-oxidative properties, and potent broad-spectrum antibacterial effects. The existing literature lacks human clinical evidence on the safety and efficacy of NO·-based treatments for DM wounds. Translating experimental favors of NO·-based treatments of DM wounds into human clinical practice needs conducting clinical trials with well-predefined effect sizes, i.e., wound reduction area, rate of wound healing, and hospital length of stay.

Debridement efficacy of serine protease and formulated cream by In Vitro assessment against artificial wound eschar

Chronic wounds typically comprise of necrotic tissue and dried secretions, often culminating in the formation of a thick and tough layer of dead skin known as eschar. Removal of eschar is imperative to facilitate wound healing. Conventional approach for eschar removal involves surgical excision and grafting, which can be traumatic and frequently leads to viable tissue damage. There has been growing interest in the use of enzymatic agents for a gentler approach to debridement, utilizing proteolytic enzymes. In this study, a purified intracellular recombinant serine protease from Bacillus sp. (SPB) and its cream formulation were employed to evaluate their ability to degrade artificial wound eschar; composed of collagen, fibrin, and elastin. Degradation was assessed based on percentage weight reduction of eschar biomass, analysis via sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), and scanning electron microscopy (SEM). Both SPB and its cream formulation were able to degrade up to 50 % artificial wound eschar, with the SPB cream maintaining its degradation efficiency for up to 24 hours. Additionally, the SPB-based cream demonstrated the ability to hydrolyze proteinaceous components of eschars individually (fibrin and collagen) as determined through qualitative assessment. These findings suggest that SPB holds promise for the debridement of wound eschar.

Time-course study of genetic changes in periodontal ligament regeneration after tooth replantation in a mouse model

This research focused on analyzing gene expression changes in the periodontal ligament (PDL) after tooth re-plantation to identify key genes and pathways involved in healing and regeneration. Utilizing a mouse model, mRNA was extracted from the PDL at various intervals post-replantation for RNA sequencing analysis, spanning from 3 to 56 days. The results revealed significant shifts in gene expression, particularly notable on day 28, supported by hierarchical clustering and principal component analysis. Gene ontology (GO) enrichment analysis highlighted an upregulation in olfactory receptor and G protein-coupled receptor signaling pathways at this time point. These findings were validated through reverse transcription-quantitative PCR (RT-qPCR), with immunochemical staining localizing olfactory receptor gene expression to the PDL and surrounding tissues. Moreover, a scratch assay indicated that olfactory receptor genes might facilitate wound healing in human PDL fibroblasts. These results underscore the importance of the 28-day post-transplant phase as a potential “tipping point” in PDL healing and regeneration. In conclusion, this research sheds light on the potential role of olfactory receptor genes in PDL regeneration, providing a foundation for developing new therapeutic approaches in tooth replantation and transplantation, with broader implications for regenerative medicine in oral health.

Melt-extruded biocompatible surgical sutures loaded with microspheres designed for wound healing

Sutures are commonly used in surgical procedures and have immense potential for direct drug delivery into the wound site. However, incorporating active pharmaceutical ingredients into the sutures has always been challenging as their mechanical strength deteriorates. This study proposes a new method to produce microspheres-embedded surgical sutures that offer adequate mechanical properties for effective wound healing applications. The study used curcumin, a bioactive compound found in turmeric, as a model drug due to its anti-inflammatory, antioxidant, and anti-bacterial properties, which make it an ideal candidate for a surgical suture drug delivery system. Curcumin-loaded microspheres were produced using the emulsion solvent evaporation method with polyvinyl alcohol (PVA) as the aqueous phase. The microspheres’ particle sizes, drug loading (DL) capacity, and encapsulation efficiency (EE) were investigated. Microspheres were melt-extruded with polycaprolactone and polyethylene glycol via a 3D bioplotter, followed by a drawing process to optimise the mechanical strength. The sutures’ thermal, physiochemical, and mechanical properties were investigated, and the drug delivery and biocompatibility were evaluated. The results showed that increasing the aqueous phase concentration resulted in smaller particle sizes and improved DL capacity and EE. However, if PVA was used at 3% w/v or below, it prevented aggregate formation after lyophilisation, and the average particle size was found to be 34.32 ± 12.82 μm. The sutures produced with the addition of microspheres had a diameter of 0.38 ± 0.02 mm, a smooth surface, minimal tissue drag, and proper tensile strength. Furthermore, due to the encapsulated drug-polymer structure, the sutures exhibited a prolonged and sustained drug release of up to 14 d. Microsphere-loaded sutures demonstrated non-toxicity and accelerated wound healing in the in vitro studies. We anticipate that the microsphere-loaded sutures will serve as an excellent biomedical device for facilitating wound healing.

Cation-π Interaction-Enhanced Self-Healing Injectable Hydrogels for Gastric Perforation Repair.

Surgical operations are the preferred treatment for gastric perforation (GP) but incur postoperative complications such as gastrointestinal adhesions and bacterial infections, leading to inefficient wound healing and serious complications that may even threaten the life of the patient. Developing hydrogel dressings capable of adapting to the gastric environment (acid) and decreasing visceral adhesions and bacterial infections after GP treatment is crucial. In this article, we developed an injectable, self-healing hydrogel using cation-π interactions between protonated amines and aromatic rings under acidic conditions and explored it for GP repair. The hydrogels demonstrate exceptional self-healing capabilities under acidic conditions and can be effectively tailored for the gastric environment. In addition, the hydrogel demonstrated significant efficacy in preventing gastrointestinal adhesion, reducing inflammation, promoting angiogenesis, and effectively facilitating wound healing in a rat GP model. This novel hydrogel demonstrates adaptability to the gastric environment, rendering it highly promising for potential applications in gastric trauma healing.

Regulating Tissue Growth Factors for Healing with Etherified Carboxymethylcellulose Matrix.

Etherified Carboxymethylcellulose Matrix (eCMC) is a revolutionary application of carboxymethylcellulose (CMC) in wound care, known for its potential in hemostasis and tissue regeneration. This study aims to investigate the mechanism of eCMC in tissue healing by establishing a rat burn model and administering eCMC as a treatment. The objective is to analyze cytokines and inflammatory mediators using a Cytokine Array and histochemical staining to understand the effects of eCMC on tissue regeneration. A rat burn model was created, and eCMC was applied as a treatment. Tissue samples were collected at multiple time points to assess the expression of cytokines and inflammatory mediators using a Cytokine Array. Additionally, histochemical staining was performed to evaluate tissue regeneration factors. eCMC induced the expression of endogenous cytokines, particularly VEGF and PDGF, while inhibiting inflammatory cytokines such as CINC-1, CINC-2, and MMP-8. This dual action facilitated wound healing and mitigated the risk of infection. eCMC demonstrates promising potential for enhancing skin regeneration. Further research is warranted to delve into the precise mechanism of eCMC's cytokine regulation. In vitro and in vivo studies should be conducted to comprehensively investigate the therapeutic capabilities of eCMC in wound healing.

The combination treatment of low voltage electrostatic field and Ultraviolet-C could accelerate the process of wound healing of potato tubers

Low voltage electrostatic field (LVEF) and ultraviolet-C (UV–C) are non-thermal, safe, and environmentally friendly preservation technologies. This study explored the efficacy of LVEF, UV-C (0.1 kJ m−2), and their combination (LVEF + UV-C) in regulating the wound-healing response of injured potato tubers over a 21-day healing period at 20 °C. Results demonstrated that LVEF + UV-C treatment showed superior efficacy in accelerating wound healing of tubers compared to single-treatment and control groups, mitigating weight loss and disease index, promoting suberin and lignin accumulation, and enhancing firmness, browning index, and H2O2 content. Biochemical changes observed during tuber healing exhibited a positive correlation with increased enzyme activities (PAL, 4CL, CAD, POD, and PPO) and metabolite levels (phenolic compounds, flavonoids, lignin) associated with phenylpropane metabolism. Our study findings suggest that the application of LVEF + UV-C stimulates phenylpropanoid metabolism, accelerates suberin and lignin accumulation at wounds, thus facilitates wound healing in potato tubers.

Bilateral Superior Gluteal Artery Perforator (SGAP) Flap: Modified Concept in Perineal Reconstruction.

Background/Objectives: Perineal reconstruction after abdominoperineal excision often requires complex closures and is fraught with wound healing complications. Flap-based approaches introduce non-irradiated vascularized tissue to the area of resection to fill a large soft-tissue defect and dead space, reduce the risk of infection, and facilitate wound healing. Employing perforator flaps with their beneficial donor site properties, the authors have developed a concept of bilateral superior gluteal artery perforator (SGAP) flaps to restore extensive perineal defects. Methods: This retrospective case series was conducted between September 2015 and December 2019. We included three patients who received bilateral SGAP flap reconstruction after oncological resection. One deepithelialized SGAP flap was used for obliteration of dead space, combined with the contralateral SGAP flap for superficial defect reconstruction and wound closure. Results: Within this patient population, two male and one female patient, with a median age of 62 years (range, 52-76 years), were included. Six pedicled SGAP flaps were performed with average flap dimensions of 9 × 20 cm (range 7-9 × 19 × 21). No flap loss or no local recurrence were documented. In one case, partial tip necrosis with prolonged serous drainage was observed, which was managed by surgical debridement. No further complications were detected. Conclusions: The combination of two SGAP flaps provides maximal soft tissue for defect reconstruction and obliteration of dead space, while maintaining a very inconspicuous donor site, even with bilateral harvesting. Given these advantages, the authors recommend this promising approach for successful reconstruction of perineal defects.

Polyphenol-mediated hyaluronic acid/tannic acid hydrogel with short gelation time and high adhesion strength for accelerating wound healing

Wound healing is a complex process involving a complicated interplay between numerous cell types and vascular systems. Hyaluronic acid (HA)-based hydrogel facilitates wound healing, and is involved in all processes. However, slow gelation speed and weak adhesion strength limit its ability to form a stable physical barrier quickly. Herein, we propose a HA-based composite hydrogel as the wound dressing based on oxidative coupling reaction. Tannic acid and dopamine-coated carbon particles (DCPs) containing abundant phenolic hydroxyl groups are incorporated into the HA-based hydrogel for increasing the number of crosslinking sites of oxidative coupling of the hydrogel and enhancing adhesion through the formation of covalent bonds and hydrogen bonds between hydrogel and wound sites. The composite hydrogel exhibits short gelation time (<6 s) and high adhesion strength (>8.1 kPa), which are superior to the references and commercial products of its kind. The in vitro experiments demonstrate that the hydrogel has low hemolytic reaction, negligible cytotoxicity, and the ability to promote fibroblast proliferation and migration. The in vivo full-thickness skin defect model experiments demonstrate that the hydrogel can accelerate wound healing under mild photothermal stimulation of DCPs by reducing inflammation, relieving tissue hypoxia, and promoting angiogenesis and epithelialization.

MoO3-X nanodots coated suture for combating surgical site infection via antibacterial and anti-inflammatory properties

Surgical site infection (SSI) significantly affects patient recovery time, health outcomes and quality of life which is closely associated with the use of implants or mesh. Sutures are the most frequently used implants that play a significant role in the development of SSI. Studies have demonstrated that the administration of effective bactericidal and anti-inflammatory treatments can significantly decrease the incidence of SSI. To address this concern, a versatile suture was engineered by coating MoO3-X nanodots in this study. The incorporation of MoO3-X nanodots endowed the suture with desirable antibacterial and anti-inflammatory properties that were evaluated in in vitro and in vivo experiments. The results showed its remarkable ability to facilitate wound healing and prevent SSI through its dual action of combating bacterial infection and reducing inflammation. These findings highlight the promising potential of this multifunctional surgical suture as a versatile tool to promote better outcomes in surgical procedures.

Silicone Bioadhesive with Shear-Stiffening Effect: Rate-Responsive Adhesion Behavior and Wound Dressing Application.

Stimuli-responsive adhesives with on-demand adhesion capabilities are highly advantageous for facilitating wound healing. However, the triggering conditions of stimuli-responsive adhesives are cumbersome, even though some of them are detrimental to the adhesive and adjacent natural tissues. Herein, a novel stimuli-responsive adhesive called shear-stiffening adhesive (SSA) has been created by constructing a poly(diborosiloxane)-based silicone network for the first time, and SSA exhibits a rate-responsive adhesion behavior. Furthermore, we introduced bactericidal factors (PVP-I) into SSA and applied it as a wound dressing to promote the healing of infected wounds. Impressively, the wound dressing not only has excellent biocompatibility and long-term antibacterial properties but also performs well in accelerating wound healing. Therefore, this study provides a new strategy for the synthesis of intelligent adhesives with force rate response, which simplifies the triggering conditions by the force rate. Thus, SSA has great potential to be applied in wound management as an intelligent bioadhesive with on-demand adhesion performance.

Bioactive Metal Ion-Coordinated Dynamic Hydrogel with Antibacterial, Immunomodulatory, and Angiogenic Activities for Infected Wound Repair.

The repair of infected wounds is a complex physiopathologic process. Current studies on infected wound treatment have predominantly focused on infection treatment, while the factors related to delayed healing caused by vascular damage and immune imbalance are commonly overlooked. In this study, an extracellular matrix (ECM)-like dynamic and multifunctional hyaluronic acid (HA) hydrogel with antimicrobial, immunomodulatory, and angiogenic capabilities was designed as wound dressing for the treatment of infected skin wounds. The dynamic network in the hydrogel dressing was based on reversible metal-ligand coordination formed between sulfhydryl groups and bioactive metal ions. In our design, antibacterial silver and immunomodulatory zinc ions were employed to coordinate with sulfhydrylated HA and a vasculogenic peptide. In addition to the desired bioactivities for infected wounds, the hydrogel could also exhibit self-healing and injectable abilities. Animal experiments with infected skin wound models indicated that the hydrogel dressings enabled minimally invasive injection and seamless skin wound covering and then facilitated wound healing by efficient bacterial killing, continuous inflammation inhibition, and improved blood vessel formation. In conclusion, the metal ion-coordinated hydrogels with wound-infection-desired bioactivities and ECM-like dynamic structures represent a class of tissue bionic wound dressings for the treatment of infected and chronic inflammation wounds.

Dual-responsive metal polyphenol network nanosheets for diabetic wound healing

Diabetic wound healing poses a significant challenge in the biomedical domain. Inadequate angiogenesis and fibroblast dysfunction are two primary characteristics of diabetic microenvironment. Fibroblast dysfunction is characterized by excessive accumulation of reactive oxygen species (ROS) and fragmented mitochondria. Herein, we developed a microenvironment responsive zinc–gallic acid nanosheets (ZnGA NSs) for diabetic wound healing, which slowly release Zn2+ and gallic acid (GA) in response to low pH and excessive ROS. The released Zn2+ enhanced cell proliferation, migration, and endothelial tube formation. And the released GA activated antioxidant enzyme system via the KEAP1/NRF2 pathway and promoted mitochondrial fusion by upregulating MFN1/2 and OPA1, which ultimately reprograms dysfunctional fibroblast. The application of ZnGA NSs effectively facilitated wound healing in a rat diabetic model with full-thickness cutaneous defects. More importantly, skin wounds treated with ZnGA NSs exhibited enhanced angiogenesis, alleviated inflammation, and improved tissue regeneration. These findings highlight the potential of ZnGA NSs as a promising therapeutic modality for diabetic wound treatment.