Wound Collagen Deposition Research Articles

The Effect of Agave Bagasse Extract on Wound Healing in a Murine Model

Background/Objectives: The development of bioproducts that can accelerate wound healing is a key focus in biomedicine, especially when these products are derived from sustainable by-products. This study investigates the wound-healing potential of an extract obtained from Agave angustifolia Haw bagasse (BagEE) using microwave extraction.Methods: HPLC-MS analysis was performed to identify the main compounds present in BagEE, revealing quercetin, isorhamnetin, diosgenin, hecogenin, manogenin, β-sitosterol glucoside, and β-sitosterol as tentative constituents. A murine excision wound model was employed to assess the efficacy of BagEE. The experimental group received a topical application of 8 mg of BagEE, while the control group was treated with water only. Wound closure, re-epithelialization, and collagen deposition were evaluated to determine the effects of BagEE on skin healing. Results: The BagEE-treated group exhibited significantly accelerated wound healing, achieving a 99.4% closure rate by day 13 compared to the control group’s 92.8% closure rate on day 22. Additionally, wounds treated with BagEE displayed complete re-epithelialization and a well-organized skin structure. Conclusions: These findings suggest that BagEE promotes effective wound healing and shows promise as a topical agent for skin regeneration. Further studies are necessary to investigate its anti-inflammatory and wound-healing activities in both in vivo and in vitro settings.

Keratin/chitosan film promotes wound healing in rats with combined radiation-wound injury

Human hair keratin, a natural protein derived from human hair, has emerged prominently in the field of wound repair, showcasing its unique regenerative capabilities and extensive application potential. However, it is a challenge for the keratin to efficiently therapy the impaired wound healing, such as combined radiation-wound injury. Here, we report a keratin/chitosan (KRT/CS) film for skin repair of chronic wounds in in rats with combined radiation-wound injury. In brief, the KRT/CS film was characterized by scanning electron microscopy (SEM), mechanical property analysis, water absorption, and swelling analysis. A rat model of combined radiation-wound injury was employed to evaluate the therapeutic efficacy of the KRT/CS film. Finally, the systemic biotoxicity of KRT/CS film was assessed through histological analysis. The surface of KRT/CS film was uniform and smooth compared with the KRT film, and the mechanical property, swelling rate and water absorption rate of KRT/CS film were significantly improved, which can meet the application requirements of wound excipient dressing. Furthermore, the combined radiation-wound injury in rats was established that the wound closure rate was achieved 74.46% after 14 days of treatment with KRT/CS film, comparing to the single KRT membrane and commercially available Band-Aids. Histological analysis demonstrated that the amount of angiogenesis and collagen deposition in wounds treated with KRT/CS were significantly improved. These findings demonstrate the KRT/CS film as a promising therapeutic agent for combined radiation-wound injury.Graphical

Herbal micelles-loaded ROS-responsive hydrogel with immunomodulation and microenvironment reconstruction for diabetic wound healing.

Persistent inflammation is a major cause of diabetic wounds that are difficult to heal. This is manifested in diabetic wounds with excessive reactive oxygen clusters (ROS), advanced glycation end products (AGE) and other inflammatory factors, and difficulty in polarizing macrophages toward inhibiting inflammation. Berberine is a natural plant molecule that inhibits inflammation; however, its low solubility limits its biological function through cytosis. In this study, we designed F127 micelles to encapsulate berberine with the aim of improving its solubility and bioavailability. Meanwhile, in order to achieve effective drug delivery at the wound site, we designed an injectable ferrocene-cyclodextrin self-assembled oxidation-reactive supramolecular hydrogel drug delivery system. Cellular experiments have shown that the hydrogel can reduce intracellular ROS and AGE production, attenuate cellular damage, promote macrophage polarization toward inhibition of inflammation, and reduce the secretion of inflammatory factors. In an animal model of diabetic mice, this hydrogel dressing reduces the level of inflammation in diabetic wounds, optimizes collagen deposition in diabetic wounds, and ultimately achieves high-quality diabetic wound healing. The work offers a straightforward and effective solution to the challenge of administering hydrophobic anti-inflammatory agents in the context of diabetic wound therapy.

An Integrated Therapeutic Nanoparticles and Quorum Quenching‐Based Microneedle Patch for Bacterial‐Infected Wound Healing

AbstractSkin injuries leading to drug‐resistant bacterial infections remain a significant challenge, posing a threat to human health. There is an urgent necessity to develop wound dressings for the treatment of such injuries. The proceeding study presents the design of a multifunctional microneedle (MNs) patch containing quorum‐quenching enzyme and manganese dioxide (MnO2) nanoparticles for treating Pseudomonas aeruginosa‐infected wounds. In co‐culture experiments with P. aeruginosa, the quorum‐quenching enzyme significantly reduced the production of virulence factors and inhibited biofilm formation. MnO2 NPs exhibited excellent scavenging ability against a wide range of free radicals when assayed in in vitro antioxidant assays. Subsequently, soluble hyaluronic acid is chosen as the substrate in order to prepare the MNs patches loaded with quorum quenching enzyme and MnO2 NPs for wound healing assessment in a P. aeruginosa‐infected mouse wound model. Evaluation of wound size and closure rate demonstrated that the patch significantly accelerated wound healing, resulting in shorter healing durations and improved wound closure. Additionally, inflammation‐related cytokine levels are reduced, indicating a lower level of inflammation. Tissue section staining shows that treatment with MNs promoted wound epithelialization, collagen deposition, and angiogenesis. The multifunctional MNs patch represents a promising treatment option for drug‐resistant bacterial infections in wound management.

The Role of Biomechanical Forces in the Formation and Treatment of Pathological Scars.

Pathological scars, including hypertrophic scar and keloid are the result of excessive tissue repair and are influenced by biomechanical forces like tension, mechanical pressure, and stiffness. These forces significantly impact scar development and progression, affecting wound healing, collagen deposition, and tissue remodeling. Understanding how these mechanical stimuli contribute to scar development is essential for devising effective therapeutic interventions. Clinically, reducing wound tension and applying mechanical pressure are key strategies for managing pathological scars. Techniques like super-tension-reduction suturing, stress-shielding polymers, and force-modulating tissue bridges (FMTB) have been shown to effectively alleviate tension and reduce scar proliferation. Additionally, Pressure Garment Therapy (PGT) is widely used to treat hypertrophic scars by reducing tissue stiffness, limiting collagen buildup, and promoting collagen realignment. Despite challenges such as discomfort and uneven pressure application, ongoing research focuses on enhancing these therapies through mechanosensitive technologies to improve both efficacy and patient comfort. This review highlights the role of biomechanical forces in scar formation and discusses therapeutic approaches that target these forces to improve clinical outcomes.

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

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

Self-assembled near-infrared-photothermal antibacterial Hericium erinaceus β-glucan/tannic acid/Fe (III) hydrogel for accelerating infected wound healing

Bacterial infection severely hinders skin wound healing, highlighting the critical application value of developing antibacterial and anti-inflammatory hydrogel dressings. In this work, we focused on β-glucan from Hericium erinaceus (HEBG) as the research object, and proposed a solvent-induced combined temperature manipulation technique to trigger multilevel self-assembly of β-glucan. Furthermore, we incorporated green synthesized near-infrared photosensitizer tannic acid (TA)/iron (III) complex into the system. A hydrogel with exceptional antibacterial properties, capable of responding to near-infrared photothermal stimuli while exhibiting remarkable stiffness and structural consistency, was successfully synthesized. Under near-infrared radiation, HEBG/TA/Fe hydrogels produced local hyperthermia and exhibited excellent antibacterial activity against bacteria-infected wounds. Moreover, the HEBG/TA/Fe hydrogel demonstrates its ability to regulate cytokines by effectively inhibiting the production of inflammatory mediators TNF-α and IL-6, while simultaneously enhancing the expression of cell proliferation factor KI-67 and markers associated with angiogenesis such as CD31 and α-SMA. Notably, the results of tissue staining revealed that the NIR + HEBG/TA/Fe5 hydrogel could effectively promoting granulation and vascularization, improving collagen deposition in infected wounds thereby accelerating the healing process. These findings indicate that mixed hydrogels exhibit potential as viable options for the treatment of bacterial infections.

Double Enzyme Active Hydrogel Program Regulates the Microenvironment of Staphylococcus aureus-Infected Pressure Ulcers.

The treatment of infected pressure ulcers (IUPs) requires addressing diverse microenvironments. A pressing challenge is to effectively enhance the regenerative microenvironment at different stages of the healing process, tailoring interventions as needed. Here, a dual enzyme mimetic and bacterial responsive self-activating antimicrobial hydrogel designed to enhance IPUs healing is introduced. This hydrogel incorporates pH-responsive dual enzyme-active nanoplatforms (HNTs-Fe-Ag) encapsulated within a methacrylate-modified silk fibroin (SFMA) and dopamine methacrylamide (DMA) matrix. This composite hydrogel exhibits adaptive microenvironment regulation capabilities. Under the low pH microenvironment of bacterial infection, it has excellent antimicrobial activity by self-activating the •OH generation in conjunction with photothermal effects. Under the neutral and alkaline microenvironment of chronic inflammation, it catalyzes the decomposition of hydrogen peroxide (H2O2) to produce oxygen (O2), thereby alleviating hypoxia and scavenging reactive oxygen species (ROS), which in turn remodulates the phenotype of macrophages. The composite hydrogel demonstrates on-demand therapeutic effects in the microenvironment of infected wounds, significantly enhancing the regenerative microenvironment of IUPs by promoting wound closure, inflammation regulation, and collagen deposition through self-activated antimicrobial action during infection and adaptive hypoxia relief during recovery. This approach offers a novel strategy for developing smart wound dressings.

Curcumin-loaded gold nanoparticles with enhanced antibacterial efficacy and wound healing properties in diabetic rats

Diabetic wounds pose a significant global health challenge. Although curcumin exhibits promising wound healing and antibacterial properties, its clinical potential is limited by low aqueous solubility, and poor tissue penetration. This study aimed to address these challenges and enhance the wound healing efficacy of curcumin by loading it onto gold nanoparticles (AuNPs). The properties of the AuNPs, including particle size, polydispersity index (PDI), zeta potential, percent drug entrapment efficiency (%EE) and UV–Vis spectra were significantly influenced by the curcumin/gold chloride molar ratio used in the synthesis of AuNPs. The optimal formulation (F2) exhibited the smallest particle size (41.77 ± 6.8 nm), reasonable PDI (0.59 ± 0.17), high %EE (94.43 ± 0.25 %), a moderate zeta potential (−8.44 ± 1.69 mV), and a well-defined surface Plasmon resonance peak at 526 nm. Formulation F2 was incorporated into Pluronic® F127 gel to facilitate its application to the skin. Both curcumin AuNPs solution and gel showed sustained drug release and higher skin permeation parameters compared with the free drug solution. AuNPs significantly enhanced curcumin’s antibacterial efficacy by lowering the minimum inhibitory concentrations and enhancing antibacterial biofilm activity against various Gram-positive and Gram-negative bacterial strains. In a diabetic wound rat model, AuNPs-loaded curcumin exhibited superior wound healing attributes compared to the free drug. Specifically, it demonstrated improved wound healing percentage, reduced wound oxidative stress, increased wound collagen deposition, heightened anti-inflammatory effects, and enhanced angiogenesis. These findings underscore the potential of AuNPs as efficacious delivery systems of curcumin for improved wound healing applications.

Activation of adenosine A2a and A2b receptors augments the skin wound healing in juvenile grass carp

Wounded fish skin leads to the impairment of internal tissue homeostasis and provides an opportunity for pathogens to invade, resulting in the occurrence of fish diseases. Accordingly, skin wound healing has been investigated in many fishes. In the present study, we found that the concentration of adenosine increased in grass carp skin wounds and antagonization of adenosine receptors aggravated the skin wound closure, implying that adenosine receptor activation played a role in fish skin wound repair. After the expression of adenosine A2a receptor (A2aR) and A2bR in grass carp skin was verified, the effects of two adenosine analogs, ZM241385 and CGS 21680, on grass carp A2aR and A2bR activation were examined by a dual-luciferase assay. The results showed that 500 nM of ZM241385 could antagonize the activation of both receptors by adenosine and 5–5000 nM of CGS 21680 could stimulate both receptors. In this scenario, these two compounds were administrated to the skin wounds of juvenile grass carp weighting about 8.0 g each, showing that 0.5, 2.5, 12.5 μg/tail of ZM241385 dose-dependently delayed while 0.8 and 2.4 μg/tail of CGS 21680 accelerated closure of the wounds when compared to the control group treated with the solvent. The thickness and cell proliferation of the epithelial layer in the wounds were decreased by 2.5 μg/tail of ZM241385 but increased by 0.8 μg/tail of CGS 21680 at 3 days post wounding compared to the control group. To our knowledge, this is the first report demonstrating the effects of adenosine receptor activation on skin re-epithelization in vertebrates. Moreover, the effects of ZM241385 and CGS 21680 on granulation formation including fibroblast migration and collagen deposition in grass carp skin wounds were also investigated in the present study. The results revealed that these two compounds oppositely regulated fibroblast migration and collagen deposition in grass carp skin wounds. These results implied that activation of grass carp A2aR and A2bR improved granulation formation in the wound, leading to enhancement of skin wound repair in juvenile grass carp. These results provide the new clues and mechanisms on the skin wound healing in fish species.

Functional poly(e-caprolactone)/SerMA hybrid dressings with dimethyloxalylglycine-releasing property improve cutaneous wound healing

Medical dressings with multifunctional properties, including potent regeneration capability and good biocompatibility, are increasingly needed in clinical practice. In this study, we reported a novel hybrid wound dressing (PCL/SerMA/DMOG) that combines electrospun PCL membranes with DMOG-loaded methacrylated sericin (SerMA) hydrogel. In such a design, DMOG molecules are released from the hybrid dressing in a sustained mannerin vitro. A series ofin vitroassays demonstrated that DMOG-loaded hybrid dressing has multiple biological functions, including promotion of human umbilical vein endothelial cells proliferation and migration,in vitrovascularization, and the generation of intracellular NO. When applied to the cutaneous wound, the PCL/SerMA/DMOG dressing significantly accelerated wound closure and tissue regeneration by promoting angiogenesis in the wound area, collagen deposition, and cell proliferation within the wound bed. These results highlight the potential clinical application of PCL/SerMA/DMOG hybrid dressings as promising alternatives for accelerating wound healing via improved biocompatibility and angiogenesis amelioration.

A multifunctional polyacrylonitrile fibers/alginate-based hydrogel loaded with chamomile extract and silver sulfadiazine for full-thickness wound healing

Most conventional wound dressings do not meet the clinical requisites owing to their limited multifunctionality. Herein, a bilayer wound dressing containing both hydrogel and fibrous structures with multifunctional features was developed for effective skin rehabilitation. Sodium alginate (SA)/gelatin (Gel) hydrogel comprising Matricaria chamomilla L extract and silver sulfadiazine (AgSD) drug as antibacterial agents was cross-linked using genipin and CaCl2. Then, the surface of the hydrogel was covered by electrospun polyacrylonitrile (PAN) nanofibers to fabricate a bilayer dressing. FESEM images revealed formation of continuous, smooth, and bead-free PAN nanofibers with excellent compatibility between hydrogel and fibers. The bilayer wound dressing exhibited satisfactory mechanical virtues including elastic modulus (2.4 ± 0.2 MPa), tensile strength (6.2 ± 0.5 MPa) and elongation at break (21.8 ± 1 %) as well as suitable swelling ratio. Such bilayer dressing revealed biodegradability, cytocompatibility and effective antibacterial performance against gram positive and gram negative strains. Release kinetics of AgSD drug followed a Fickian diffusion mechanism, ensuring sustained drug release. In vivo studies demonstrated bilayer dressing could promote rate of wound closure, re-epithelialization and collagen deposition, facilitating the replacement of damaged skin with healthy tissue. Such engineered wound dressing has a high potency for inducing skin repair and could be used in skin tissue engineering.

Polyphenol hydroxytyrosol present olive oil improves skin wound healing of diabetic mice.

The imbalance in oxidant production and chronic inflammation are the main mechanisms that lead to the detrimental effects of diabetes on skin wound healing. Thus, administration of antioxidants could improve diabetic wound healing. This study aimed to understand the effects of extra virgin olive oil (EVOO) or hydroxytyrosol (HT) in skin wound healing under diabetic conditions. Skin wounds in streptozotocin-induced diabetic mice were topically treated with HT. Some diabetic animals were fed with a diet rich in EVOO. Wounds were harvested 7 days later. In in vitro assays, fibroblasts and macrophages were treated with high levels of glucose and HT. The EVOO or HT promoted wound closure and collagen deposition in diabetic mouse wounds. The EVOO or HT reduced the number of infiltrated neutrophils, tumour necrosis factor-α, lipid peroxidation, and nuclear factor erythroid 2-related factor 2 in diabetic mouse wounds. The EVOO or HT also increased the number of macrophages with anti-inflammatory phenotype and interleukin-10 in diabetic mouse wounds. In the in vitro assays, HT promoted the fibroblast migration, collagen gel contraction, and switched macrophages to an anti-inflammatory phenotype under high glucose conditions. In conclusion, the diet supplementation with EVOO or topical application of HT promotes skin wound healing under diabetic conditions and can be a possible therapeutic tool for the treatment of those lesions.

Enhancing Wound Healing With Sprayable Hydrogel Releasing Multi Metallic Ions: Inspired by the Body's Endogenous Healing Mechanism.

In the pursuit of new wound care products, researchers are exploring methods to improve wound healing through exogenous wound healing products. However, diverging from this conventional approach, this work has developed an endogenous support system for wound healing, drawing inspiration from the body's innate healing mechanisms governed by the sequential release of metal ions by body at wound site to promote different stages of wound healing. This work engineers a multi-ion-releasing sprayable hydrogel system, to mimic this intricate process, representing the next evolutionary step in wound care products. It comprises Alginate (Alg) and Fibrin (Fib) hydrogel infused with Polylactic acid (PLA) polymeric microcarriers encapsulating multi (calcium, copper, and zinc) nanoparticles (Alg-Fib-PLA-nCMB). Developed sprayable Alg-Fib-PLA-nCMB hydrogel show sustained release of beneficial multi metallic ions at wound site, offering a range of advantages including enhanced cellular function, antibacterial properties, and promotion of crucial wound healing processes like cell migration, ROS mitigation, macrophage polarization, collagen deposition, and vascular regeneration. In a comparative study with a commercial product (Midstress spray), developed Alg-Fib-PLA-nCMB hydrogel demonstrates superior wound healing outcomes in a rat model, indicating its potential for next generation wound care product, addressing critical challenges and offering a promising avenue for future advancements in the wound management.

Copper doped carbon dots modified bacterial cellulose with enhanced antibacterial and immune regulatory functions for accelerating wound healing

The microenvironment of wound healing is susceptible to bacterial infection, chronic inflammation, oxidative stress, and inadequate angiogenesis, requiring the development of innovative wound dressings with antibacterial, anti-inflammatory, antioxidant, and angiogenic capabilities. This research crafted a new multifunctional bacterial cellulose composite membrane infused with copper-doped carbon dots (BC/Cu(II)-RCDs). Findings validated the successful loading of copper-doped carbon dots onto the BC membrane via hydrogen bonding interactions. Compared to the pure BC membrane, the BC/Cu(II)-RCDs composite membrane exhibited significantly enhanced hydrophilicity, tensile properties, and thermal stability. Diverse in vitro assays demonstrated excellent biocompatibility and antibacterial activity of BC/Cu(II)-RCDs composite membranes, alongside their ability to expedite the inflammatory phase and stimulate angiogenesis. In vivo trials corroborated the membrane's ability to foster epithelial regeneration, collagen deposition, and tissue regrowth in full-thickness skin wounds in rats while also curbing inflammation in infected full-thickness skin wounds. More importantly, the treatment of the BC/Cu(II)-RCDs composite membrane may result in the activation of VEGF and MAPK signaling proteins, which are key players in cell migration, angiogenesis, and skin tissue development. In essence, the developed BC/Cu(II)-RCDs composite membrane shows promise for treating infected wounds and serves as a viable alternative material for medicinal bandages.

Multi-responsive sodium hyaluronate/tannic acid hydrogels with ROS scavenging ability promote the healing of diabetic wounds

Oxidative stress caused by excessive reactive oxygen species (ROS) accumulation significantly hinders wound healing in patients with diabetes. Scavenging ROS and reducing inflammation are crucial for rapid healing. In this work, a multi-responsive sodium hyaluronate (HA)/tannic acid (TA) hydrogel was developed based on boronate ester bonds. Sodium hyaluronate with 3-aminophenyl boronic acid modification (HA-APBA) was mixed and crosslinked with TA to form HA-APBA/TA hydrogels. These hydrogels are injectable, self-healing, and biocompatible. The HA-APBA/TA hydrogels could release free TA through the collapse of the structure at low pH, high H2O2 concentration, and high glucose concentration, thus possessing good ROS scavenging ability. In full-thickness skin wounds of db/db mice, the HA-APBA/TA hydrogels promoted wound healing, collagen deposition, and significant angiogenesis. Furthermore, they have been shown to effectively reduce the levels of inflammatory factors in wounds and lower the expression of CD86, a pro-inflammatory macrophage surface marker. This resulted in a more effective transition of wound healing from the inflammatory phase to the proliferative phase. This study provides an optional strategy for alleviating oxidative stress and controlling excessive inflammation, thereby promoting diabetic wound healing.

A multifunctional hydrogel with mild photothermal antibacterial and antioxidant properties based on quercetin and dopamine-coated zinc oxide nanoparticles for healing bacteria-infected wound

Bacterial infection and inflammation hinder the natural healing process of skin wounds and may also cause wound complications. In light of the aforementioned considerations, this study developed an antibacterial and antioxidant QT/PDA@ZnO /QCS/(PAM-PAMPS) hydrogel (QPQH). The hydrogel dressing employs a dual network structure and incorporates quercetin (QT), quaternary ammonium salt chitosan (QCS), and polydopamine-coated zinc oxide nanoparticles (PDA@ZnO NPs) into a Polyacrylamide–Poly(2-acrylamido-2-methyl-1-propanesulfonic acid)（PAM-co-AMPS）hydrogel. This design enables QPQH to exhibit good mechanical properties, remarkable adhesion properties, and the capacity to adhere closely to the wound. The mild photothermal properties (˃50 °C) and Zn2+ release ability of PDA@ZnO NPs can cooperate with the destruction ability of QCS to bacterial cell membranes, thereby achieving efficient sterilization. This process has been demonstrated to be effective against Staphylococcus aureus and Escherichia coli, with approximately 98.5 % and 99.8 % efficiency, respectively. The incorporation of QT into hydrogel confers excellent antioxidant properties, which serve to reduce oxidative stress in wounds and prevent inflammation. Furthermore, hydrogel displays favorable blood compatibility and cell compatibility, facilitating the repair of bacteria-Infected wounds and promoting angiogenesis and collagen deposition in skin wounds. In conclusion, the antibacterial and antioxidant QPQH dressing has considerable potential for clinical use in the treatment of bacteria-Infected wounds.

Integrating Bioactive Graded Hydrogel with Radially Aligned Nanofibers to Dynamically Manipulate Wound Healing Process.

Skin wound healing is a complex process that requires appropriate treatment and management. Using a single scaffold to dynamically manipulate angiogenesis, cell migration and proliferation, and tissue reconstruction during skin wound healing is a great challenge. We developed a hybrid scaffold platform that integrates the spatiotemporal delivery of bioactive cues with topographical cues to dynamically manipulate the wound-healing process. The scaffold comprised gelatin methacryloyl hydrogels and electrospun poly(ε-caprolactone)/gelatin nanofibers. The hydrogels had graded cross-linking densities and were loaded with two different functional bioactive peptides. The nanofibers comprised a radially aligned nanofiber array layer and a layer of random fibers. During the early stages of wound healing, the KLTWQELYQLKYKGI peptide, which mimics vascular endothelial growth factor, was released from the inner layer of the hydrogel to accelerate angiogenesis. During the later stages of wound healing, the IKVAVS peptide, which promotes cell migration, synergized with the radially aligned nanofiber membrane to promote cell migration, while the nanofiber membrane also supported further cell proliferation. In an in vivo rat skin wound-healing model, the hybrid scaffold significantly accelerated wound healing and collagen deposition, and the ratio of type I to type III collagen at the wound site resembled that of normal skin. The prepared scaffold dynamically regulated the skin tissue regeneration process in stages to achieve rapid wound repair with clinical application potential, providing a strategy for skin wound repair.

Preclinical Therapeutic Efficacy of Extracellular Vesicles Derived from Adipose-Derived Mesenchymal Stromal/Stem Cells in Diabetic Wounds: a Systematic Review and Meta-Analysis.

Extracellular vesicles isolated from adipose tissue-derived mesenchymal stromal/stem cells (ADSC-EVs) have demonstrated promising potential in wound healing treatment. To determine the therapeutic efficacy of ADSC-EVs for diabetic wounds in preclinical models, we performed a meta-analysis of available studies. PubMed and Embase were searched (to April 23, 2023). All full-text articles describing the therapeutic application of ADSC-EVs in diabetic wounds were included. Study outcomes were pooled using a random effects meta-analysis, including wound closure, angiogenesis, and collagen deposition. Other outcomes were only discussed descriptively. Seventy unique records were identified from our search; 20 full-text articles were included for qualitative analysis. Twelve studies were eligible for quantitative meta-analysis. The results showed that ADSC-EVs accelerated diabetic wound healing compared to controls with a large effect (standardized mean difference (SMD) 4.22, 95% confidence interval (CI) 3.07 to 5.36). The administration of ADSC-EVs also improved neovascularization (SMD 9.27, 95% CI 4.70 to 13.83) and collagen deposition (SMD 2.19, 95% CI 0.94 to 3.44), with a large effect. The risk of bias was unclear in all included studies. Conclusively, ADSC-EV is an effective treatment for diabetic wounds in preclinical trials, and it appears justified for transfer into the clinical field.

IGF-1 inhibits inflammation and accelerates angiogenesis via Ras/PI3K/IKK/NF-κB signaling pathways to promote wound healing

Exogenous insulin-like growth factor-1 (IGF-1) has been reported to promote wound healing through regulation of vascular endothelial cells (VECs). Despite the existing studies of IGF-1 on VEC and its role in angiogenesis, the mechanisms regarding anti-inflammatory and angiogenetic effects of IGF-1 remain unclear. In this study, we investigated the wound-healing process and the related signaling pathway of IGF-1 using an inflammation model induced by IFN-γ. The results demonstrated that IGF-1 can increase cell proliferation, suppress inflammation in VECs, and promote angiogenesis. In vivo studies further confirmed that IGF-1 can reduce inflammation, enhance vascular regeneration, and improve re-epithelialization and collagen deposition in acute wounds. Importantly, the Ras/PI3K/IKK/NF-κB signaling pathways was identified as the mechanisms through which IGF-1 exerts its anti-inflammatory and pro-angiogenic effects. These findings contribute to the understanding of IGF-1′s role in wound healing and may have implications for the development of new wound treatment approaches.