Promote Wound Healing Research Articles

Leveraging the Physicochemical Attributes of Biomimetic Hydrogel Nanocomposites in Stem Cell Differentiation.

The field of tissue engineering has witnessed significant advancements with the advent of hydrogel nanocomposites (HNC), emerging as a highly promising platform for regenerative medicine. HNCs provide a versatile platform that significantly enhances the differentiation of stem cells into specific cell lineages, making them highly suitable for tissue engineering applications. By incorporating nanoparticles, the mechanical properties of hydrogels, such as elasticity, porosity, and stiffness, are improved, addressing common challenges such as short-term stability, cytotoxicity, and scalability. These nanocomposites also exhibit enhanced biocompatibility and bioavailability, which are crucial to their effectiveness in clinical applications. Furthermore, HNCs are responsive to various triggers, allowing for precise control over their chemical properties, which is beneficial in creating 3D microenvironments, promoting wound healing, and enabling controlled drug delivery systems. This review provides a comprehensive overview of the production methods of HNCs and the factors influencing their physicochemical and biological properties, particularly in relation to stem cell differentiation and tissue repair. Additionally, it discusses the challenges in developing HNCs and highlights their potential to transform the field of regenerative medicine through improved mechanotransduction and controlled release systems.

Three in One with Dual-Functional Hydrogel of Lactoferrin/NZ2114/LMSH Promoting Staphylococcus aureus-Infected Wound Healing.

Wound infections caused by Staphylococcus aureus often result in localized suppurative lesions that severely impede the healing process, so it is urgent to develop a dress with efficient antimicrobial and pro-healing functions. In this study, the bifunctional injectable hydrogel lactoferrin (Lf)/NZ2114/lithium magnesium silicate hydrogel (LMSH) was first successfully prepared through the electrostatic interaction method. The physical, biological, and efficacy properties are systematically analyzed with good shear-thinning capacity and biocompatibility. More importantly, it inhibits infection and promotes wound healing in a mouse wound infection model after 14 d treatment, and the bactericidal rate and healing rate were over 99.92% and nearly 100%, respectively. Meanwhile, the massive reduction of inflammatory cells, restoration of tissue structure, and angiogenesis in mice showed the anti-inflammatory and pro-healing properties of the hydrogel. The healed wounds showed thickening with more hair follicles and glands, suggesting that the hydrogel Lf/NZ2114/LMSH (Three in One) could be a better dressing candidate for the treatment of S. aureus-induced wound infections.

Amoxicillin-laded sodium alginate/cellulose nanocrystals/polyvinyl alcohol composite nanonetwork sponges with enhanced wound healing and antibacterial performance

Wound healing is a complex process and reuires a long repair process. Poor healing effect is normally a challenge for wound healing. Designing sponge dressings with drug-assisted therapy, good breathability, and multiple functional structures effectively promotes wound healing. In this work, a flexible amoxicillin-laded (AMX) sodium alginate (SA)/cellulose nanocrystals (CNCs)/ polyvinyl alcoho (PVA) (SA/CNCs/PVA-AMX, SCP-AMX) wound dressing was designed and built with an excellent porous structure, suitable porosity, and anti-bacterial properties for promoting wound tissue reparation. The porous structure of the wound dressing was fabricated by freeze-thawing cyclic and freeze-dried molding process. This wound dressing exhibited a 3D porous structure for soft-tissue-engineering application, including high porosity (84.2%), swelling ratio (1513%), tensile strength (1.79 MPA), and flexibility. With the inhibition zones of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) being 1.96 and4.58 cm, respectively, this wound dressing demonstrated good antibacterial activity against E. coli and S. aureus. More importantly, wound healing assay in vivo indicates that SCP-AMX could inhibit wound infection, promote collagen deposition, reduce inflammation, and accelerate granulation tissue and wound healing. Thus, the reported wounding dressings present excellent biocompatibility, high antibacterial activities, and excellent biosafety with great potential in wound healing applications.

Photo-Crosslinked Pro-Angiogenic Hydrogel Dressing for Wound Healing.

Severe burns are one of the most devastating injuries, in which sustained inflammation and ischemia often delay the healing process. Pro-angiogenic growth factors such as vascular endothelial growth factor (VEGF) have been widely studied for promoting wound healing. However, the short half-life and instability of VEGF limit its clinical applications. In this study, we develop a photo-crosslinked hydrogel wound dressing from methacrylate hyaluronic acid (MeHA) bonded with a pro-angiogenic prominin-1-binding peptide (PR1P). The materials were extruded in wound bed and in situ formed a wound dressing via exposure to short-time ultraviolet radiation. The study shows that the PR1P-bonded hydrogel significantly improves VEGF recruitment, tubular formation, and cell migration in vitro. Swelling, Scanning Electron Microscope, and mechanical tests indicate the peptide does not affect the overall mechanical and physical properties of the hydrogels. For in vivo studies, the PR1P-bonded hydrogel dressing enhances neovascularization and accelerates wound closure in both deep second-degree burn and full-thickness excisional wound models. The Western blot assay shows such benefits can be related to the activation of the VEGF-Akt signaling pathway. These results suggest this photo-crosslinked hydrogel dressing efficiently promotes VEGF recruitment and angiogenesis in skin regeneration, indicating its potential for clinical applications in wound healing.

Comparison of The Effectiveness of Thymoquinone, St. John Wort Oil and Silver Sulfadiazine in Experimental Burn Wounds.

We aimed to compare the effectiveness of thymoquinone (TQ), most important bioactive component of black cumin, St. John wort (SJW) oil, a traditional medicinal plant used in burns, and silver sulfadiazine (AgSD), well-known anti-inflammatory agent used in modern medicine, in an experimental burn rat-model. 63 Wistar-Albino rats were randomly divided into 9 groups (n=7). TQ, SJW were administered topically and systemically but AgSD was applied topically. Epithelialization, inflammatory cell response, granulation tissue, vascularization, and fibrosis were evaluated. Malondialdehyde (MDA), total antioxidant status (TAS), total oxidant status (TOS), vitamin E, 8-hydroxy-deoxyguanosine (8-OHdG), coenzyme Q10 (CoQ10) were analyzed in serum. Topical TQ accelerated theepithelialization, enabled granulation, vascularization and fibrosis in wounds (P=0.001). Topical and systemic TQ increased Vitamin-E levels (P=0.003) but reduced TOS and 8-OHdG levels (P=0.001). Topical SJW reduced granulation and vascularization. Topical and systemic SJW decreased TOS, MDA and 8-OHdG levels (P=0.001), but increased TAS (P=0.001), and Vitamin-E levels (P=0.003). Topical AgSD reduced TOS, 8-OHdG, MDA levels (P=0.001). Topical and systemic TQ demonstrated significant advantages in accelerating wound healing process, while also enhancing antioxidant defenses and reducing oxidative damage. SJW oil, particularly in topical application, improved epithelialization and antioxidant status but showed less efficacy in systemic use. AgSD, while effective in reducing oxidative stress, was less successful in promoting wound healing and appeared to delay granulation and fibrosis. TQ offers superior protective and healing benefits, SJW is effective locally but less so systemically, and AgSD should be used cautiously, potentially combined with antioxidants to mitigate its negative impact on wound healing.

Recent Progress of Electrospun Nanofiber Dressing in the Promotion of Wound Healing.

The nanofiber materials of three-dimensional spatial structure synthesized by electrospun have the characteristics of high porosity, high specific surface area, and high similarity to the natural extracellular matrix (ECM) of the human body. These are beneficial for absorbing wound exudate, effectively blocking the invasion of external bacteria, and promoting cell respiration and proliferation, which provides an ideal microenvironment for wound healing. Moreover, electrospun nanofiber dressings can flexibly load drugs according to the condition of the wound, further promoting wound healing. Recently, electrospun nanofiber materials have shown promising application prospects as medical dressings in clinical. Based on current research, this article reviewed the development history of wound dressings and the principles of electrospun technology. Subsequently, based on the types of base material, polymer-based electrospun nanofiber dressing and electrospun nanofiber dressing containing drug-releasing factors were discussed. Furthermore, the application of electrospun nanofiber dressing on skin tissue is highlighted. This review aims to provide a detailed overview of the current research on electrospun nanomaterials for wound healing, addressing challenges and suggesting future research directions to advance the field of electrospun dressings in wound healing.

Near-Infrared Stimuli-Responsive Hydrogel Promotes Cell Migration for Accelerated Diabetic Wound Healing.

Diabetic wound healing including diabetic foot ulcers is a major clinical challenge, which could bring an increased level of mortality and morbidity. However, conventional wound dressings exhibit limited healing efficacy due to their lack of active modulation for the healing process. Here, a near-infrared (NIR) stimuli-responsive composite hydrogel dressing with the synergistic effect of both mechanical contraction and epithelial-mesenchymal transition (EMT) was developed to facilitate cell migration and vascularization for diabetic wound healing. In the methacrylated gelatin-based composite hydrogel, N-isopropylacrylamide and polydopamine nanoparticles were incorporated to endow the composite hydrogel with thermosensitive and photothermal properties. Linagliptin (LIN) was loaded into the composite hydrogel, and the drug release rate could be controlled by NIR laser irradiation. NIR-triggered on-demand active contraction of wound area and LIN release for biological stimulation were potentially realized in this responsive system due to the thermally induced sol-gel transition of the composite hydrogel. The release of loaded LIN could effectively promote cell migration by activating EMT and enhancing angiogenesis. In the full-thickness skin defect model, the LIN-loaded composite hydrogel with NIR laser irradiation had the highest wound closure rate as compared with the pure hydrogel and LIN-loaded hydrogel groups. Therefore, this composite hydrogel can serve as an excellent platform for promoting wound healing and will find more practical value in clinical treatment.

Environmental fluoxetine promotes skin cell proliferation and wound healing

This study investigates the effects of environmentally-relevant concentrations of fluoxetine (FLX, commercial name: Prozac) on wound healing. Pollution of water systems with pharmaceutical and personal care products, including antidepressants such as FLX and other selective serotonin reuptake inhibitors, is a growing environmental concern. Environmentally-relevant FLX concentrations are known to impact physiological functions and behaviour of aquatic animals, however, the effects of exposure on humans are currently unknown. Using a combination of human skin biopsies and a human keratinocyte cell line, we show that exposure to environmental FLX promotes wound closure. We show dose-dependent increases in wound closure with FLX concentrations from 125 ng/l. Using several –omics and pharmaceutical approaches, we demonstrate that the mechanisms underlying enhanced wound closure are increased cell proliferation and serotonin signalling. Transcriptomic analysis revealed 350 differentially expressed genes after exposure. Downregulated genes were enriched in pathways related to mitochondrial function and metabolism, while upregulated genes were associated with cell proliferation and tissue morphogenesis. Kinase profiling showed altered phosphorylation of kinases linked to the MAPK pathway. Consistent with this, phosphoproteomic analyses identified 235 differentially phosphorylated proteins after exposure, with enriched GO terms related to cell cycle, division, and protein biosynthesis. Treatment of skin biopsies and keratinocytes with ketanserin, a serotonin receptor antagonist, reversed the increase in wound closure observed upon exposure. These findings collectively show that exposure to environmental FLX promotes wound healing through modulating serotonin signalling, gene expression and protein phosphorylation, leading to enhanced cell proliferation. Our results justify a transition from the study of behavioural effects of environmental FLX in aquatic animals to the investigation of effects of exposure on wound healing in aquatic and terrestrial animals, including direct impacts on human health.

Effect of extracorporeal shock wave therapy on the microbial community in burn scars: retrospective case-control study.

The effectiveness of extracorporeal shock wave therapy (ESWT) has been demonstrated in various medical fields, including burn medicine. It promotes wound healing, improves blood flow, and modulates the inflammatory responses. The recovery speed and outcomes of skin diseases are influenced by the skin microbiome; however, studies examining the effects of specific treatments on the skin microbiome are lacking. This study investigated the impact of ESWT on the skin microbiome of burn patients, focusing on the microbial diversity and community structure within burn scars. In the retrospective case-control study, nineteen patients with burn scars were treated with ESWT, and changes in their skin microbiome were evaluated. ESWT was administered weekly for three months, and samples were collected from the ESWT-treated burn scars and untreated normal skin. Blood chemistry, and pain and itching scores were evaluated during sample collection. The collected samples were then subjected to 16S rRNA sequencing. Microbial community analysis was conducted using the QIIME2 and R packages. After ESWT, changes in alpha diversity indices were observed in burn scars. Faith phylogenetic diversity (P<0.05) and observed features (P<0.01) increased, whereas the evenness index decreased (P<0.01); no marked changes were noted in untreated skin. Beta diversity analysis showed stable microbial community structures in both the treated and untreated areas. A considerable increase in Micrococcus and Staphylococcus abundance was observed. Network analysis revealed a more open microbial network structure after ESWT, indicating adaptive changes in the microbial community. ESWT enhances microbial diversity and modifies microbial community structure in burn scars, promoting a more balanced and functionally supportive microbiome. ESWT aids in scar remodeling and positively influences skin microbiome dynamics, contributing to improved skin health and recovery.

Tibial transverse transport promotes wound healing in diabetic foot ulcers by stimulating endothelial progenitor cell mobilization and homing mediated neovascularization

Background Diabetic foot ulcers (DFUs) are a common and serious complication of diabetes, often leading to amputation and decreased quality of life. Current treatment methods have limited success rates, highlighting the need for new approaches. This study investigates the potential of tibial transverse transport (TTT) to promote wound healing in DFUs. Methods To test this hypothesis, the study used New Zealand White rabbits to establish a diabetic model and simulate foot ulcers, followed by the treatment of unilateral TTT or bilateral TTT. The study employed histological analysis, flow cytometry, ELISA, and qPCR to assess the impact of TTT on tissue repair and endothelial progenitor cell (EPC) mobilization and homing, aiming to understand the underlying biological processes in wound healing. Results TTT significantly enhanced wound healing in diabetic rabbit foot ulcers. Specifically, bilateral TTT led to complete wound healing by day 19, faster than the unilateral TTT group, which healed by day 26, and the sham operation group, which nearly healed by day 37. Histological analysis showed improved tissue architecture, collagen deposition, and neovascularization in TTT-treated groups. Furthermore, TTT treatment resulted in a significant increase in VEGFR2 expression and VEGFR2/Tie-2 positive cells, particularly in the bilateral group. These findings were corroborated by qPCR results, which showed increased expression of VEGFA and CXCL12 by TTT. Conclusions: TTT may be a promising treatment for DFUs, significantly enhancing wound healing by stimulating EPC mobilization and homing mediated angiogenesis. This novel approach could substantially improve treatment outcomes for diabetic patients with chronic foot ulcers.

Human Placenta Extract (HPH) Suppresses Inflammatory Responses in TNF-α/IFN-γ-Stimulated HaCaT Cells and a DNCB Atopic Dermatitis (AD)-Like Mouse Model.

Atopic dermatitis (AD), a chronic inflammatory disease, severely interferes with patient life. Human placenta extract (HPH; also known as human placenta hydrolysate) is a rich source of various bioactive substances and has widely been used to dampen inflammation, improve fatigue, exert anti-aging effects, and promote wound healing. However, information regarding HPH's incorporation in AD therapies is limited. Therefore, this study aimed to evaluate HPH's effective potential in treating AD using tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated human keratinocytes (HaCaT), immunized splenocytes, and a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model. In TNF-α /IFN-γ-stimulated HaCaT cells, HPH markedly reduced the production of reactive oxygen species (ROS) and restored the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase 1(SOD1), catalase, and filaggrin (FLG). HPH reduced interleukin (IL)-6; thymus- and activation-regulated chemokine (TARC); thymic stromal lymphopoietin (TSLP); and regulated upon activation, normal T cell expressed and presumably secreted (RANTES) levels and inhibited nuclear factor kappa B phosphorylation. Additionally, HPH suppressed the T helper 2 (Th2) immune response in immunized splenocytes. In the AD-like mouse model, it significantly mitigated the DNCB-induced elevation in infiltrating mast cells and macrophages, epidermal thickness, and AD symptoms. HPH also reduced TSLP levels and prevented FLG downregulation. Furthermore, it decreased the expression levels of IL-4, IL-5, IL-13, TARC, RANTES, and immunoglobulin E (IgE) in serum and AD-like skin lesion. Overall, our findings demonstrate that HPH effectively inhibits AD development and is a potentially useful therapeutic agent for AD-like skin disease.

Phytic acid-loaded polyvinyl alcohol hydrogel promotes wound healing of injured corneal epithelium through inhibiting ferroptosis

As the important barrier of intraocular tissue, cornea is easy to suffer various kinds of injuries. Among them, acute alkali burn is a thorny ophthalmic emergency event, which can lead to corneal persistent epithelial defects, ulcers, and even perforation. Ferroptosis, a mode of regulatory cell death, has been found to play a key role in the process of corneal alkali burn, of which lipid peroxidation and intracellular iron levels are considered to be the possible therapeutic targets. To seek new effective treatments, the study herein focused on the occurrence of oxidative stress and ferroptosis in corneal alkali burn, exploring the role of phytic acid (PA), a natural small molecule with both antioxidant and iron chelating capacity, in the repair of corneal epithelial injury. The in vivo therapeutic results showed that PA eyedrops treatment promoted the recovery of corneal morphology and function, and in vitro experiments proved that PA prompted the repair of oxidative stress induced-corneal epithelial injury through ferroptosis inhibition. In addition, better drug treatment effect could be achieved through hydrogel delivery and sustained release, and our in vivo experiments showed the superior therapeutic effects of PA delivered by PVA hydrogels with larger molecular weights on corneal injury. In summary, this study demonstrated the excellent effect of natural small molecule PA with antioxidant and high efficiency chelating ferrous ions on ferroptosis inhibition, and showed the outstanding application prospect of PVA/PA hydrogels in the treatment of corneal epithelial injury.

All-natural hydrogel composed of carboxymethyl chitosan and oxidized dextran for promoting wound healing by immune-microenvironment regulation

Chronic wound treatment has always been a major clinical challenge owing to complex and dynamic wound microenvironment. The design and development of effective management with antimicrobial activity, ROS-scavenging and regulation immune response is vital for tissue repair. Herein, we developed puerarin (PUE) loaded a double network hydrogel consisting of methacrylated carboxymethyl chitosan and oxidized dextran with Schiff base and photo-crosslinking reaction. The composite hydrogel presented fast self-healing and outstanding compressive performance to bear deformation. The hydrogel exhibits a cumulative drug release pattern with biphasic release, which offers great potential for accelerating tissue healing at all stages of wounding. In addition, the hydrogel has good biocompatibility, antimicrobial ability and tube-forming ability in vitro. The full-thickness skin wound model of Staphylococcus aureus infection showed that the hydrogel dressing can accelerate tissue repair. This study demonstrated that the design of combing natural biomacromolecules with traditional Chinese medicine could be severed as a promising candidate biomaterial for skin tissue recovery.

Exploring grape pomace extracts for the formulation of new bioactive multifunctional chitosan/alginate-based hydrogels for wound healing applications

Chronic wounds incidence is increasing and affects millions of people around the world, causing great psychological and socio-economic impacts. However, treatments that can effectively promote wound healing are still lacking. In this study, grape pomace (GP), the main residue from winemaking production was explored as a source of high added-value raw material directed for the topical treatment of Staphylococcus aureus chronic wound infections. Crude GP extracts (composed of stalks or a skin and seeds mixture–from red and white grape varieties) obtained using a modified solid-liquid extraction (water, ethanol, and acetone solvents) were evaluated for their antioxidant capacity (ABTS and DPPH assays), as well as the richness of phenolic compounds (total phenolic content-TPC, total flavonoid content-TFC, and HPLC-DAD assays). The GP extracts with the most favorable results were incorporated in a chitosan-alginate hydrogel (cross-linked with glutaraldehyde and calcium chloride), characterized (swelling, degradation, and release properties), and tested for its bioactivity (antioxidant and antimicrobial potential). TPC and TFC were higher in red GP extracts, as confirmed by the HPLC analysis, indicating a greater diversity of compounds in these extracts. Ethanolic white GP extracts (from skin-seeds mixture) showed the highest extraction yield and antioxidant activity. Their incorporation into the chitosan-alginate hydrogel improved its swelling and antimicrobial properties (total cytoplasmic membranes disruption and culturability reduction). A biomaterial with high swelling capacity and antibacterial activity against S. aureus was obtained, which can potentially promote wound healing by exudate absorption and infection clearance while promoting valorization of by-products and stimulating a circular economy.

Highly biocompatible, antioxidant and antibacterial gelatin methacrylate/alginate - Tannin hydrogels for wound healing

Gelatin (Gel) hydrogels are widely utilized in various aspects of tissue engineering, such as wound repair, due to their abundance and biocompatibility. However, their low strength and limited functionality have constrained their development and scope of application. Tannic acid (TA), a naturally occurring polyphenol found in plants and fruits, has recently garnered interest as a crosslinking, anti-inflammatory, and antioxidant agent. In this study, we fabricated novel multifunctional gelatin methacrylate/alginate-tannin (GelMA/Alg-TA) hydrogels using chemical and physical crosslinking strategies with gelatin methacrylate (GelMA), alginate (Alg), and TA as the base materials. The GelMA/Alg-TA hydrogels maintained a stable three-dimensional porous structure with appropriate water content and exhibited excellent biocompatibility. Additionally, these hydrogels demonstrated significant antioxidant and antibacterial properties and substantially promoted wound healing in a mouse model of full-thickness skin defects by modulating inflammatory responses and enhancing granulation formation. Therefore, our study offers valuable insights into the design principles of novel multifunctional GelMA/Alg-TA hydrogels, highlighting their exceptional biocompatibility, antioxidant, and antibacterial properties. GelMA/Alg-TA hydrogels are promising candidates for wound healing applications.

Biocompatible Native Hyaluronan Nanofibers Fabricated via Aqueous PEO-Assisted Electrospinning and Heat-Quench Process.

Hyaluronan (HA) is widely used in cosmetic and biomedical applications due to its excellent biocompatibility and potential to promote wound healing. Nanofibrous HA, mimicking the extracellular matrix (ECM), is considered promising for therapeutic and cosmetic applications. However, the electrospinning process of HA often necessitates cytotoxic solvents and chemical modifications, compromising its biocompatibility and advantageous properties. In this study, poly(ethylene oxide) (PEO) was added to an aqueous solution of natural HA to improve its spinnability, enabling HA to be electrospun into fibers. The HA was rendered water-insoluble by treatment with an acidic solution, and the amorphized PEO, achieved by heat-quenching, was removed through water washing. This method distinguishes it from previous reports of fibers blended with PEO or other water-soluble polymers. Consequently, the resulting HA gel fibers demonstrated suitability for mesenchymal stem cell adhesion due to the exposure of HA on the fiber surface. Additionally, HA fibers were successfully applied directly onto the skin using a hand-held electrospinning device, indicating the potential for point-of-care and home use applications.

Blood-responsive mussel-inspired hydrogels for hemostasis, antibacterial action, and wound healing

Rapid hemostasis, potent antimicrobial activity, and efficient wound management are critical factors in enhancing the survival of trauma patients. Chitosan, as a green and sustainable biomaterial with low cost, degradability and biocompatibility, is widely used in the biomedical field. However, chitosan dissolves in an acidic environment, which is not conducive to wound healing. In this study, chitosan was chemically modified to address this limitation. A mussel-inspired hydrogel composed of caffeic acid-grafted chitosan, gallic acid-grafted chitosan, and oxidized microcrystalline cellulose (CHI-C/CSG/OMCC) was designed. This hydrogel exhibits blood-responsive gelation behavior and offers a synergistic combination of tissue adhesion, antimicrobial properties, and tissue repair capabilities. The carboxyl, hydroxyl, phenolic hydroxyl and aldehyde groups within the hydrogel system endowed the hydrogel with excellent adhesion properties (53.1 kPa adhesion strength to porcine skin-adherent tissues), biocompatibility, and excellent antimicrobial properties. Surprisingly, this hydrogel not only achieved rapid and effective hemostasis, but also effectively promoted wound healing in a mouse skin injury model. In addition, its remarkable efficacy in stopping bleeding within approximately 2 min without rebleeding was demonstrated in a porcine model of acute gastrointestinal hemorrhage in the esophagus, stomach, and intestines. This blood-responsive ternary hydrogel offers a promising alternative to wound management materials due to its excellent overall performance and superior efficacy in all phases of wound healing.

MSC Exosomes Containing Valproic Acid Promote Wound Healing by Modulating Inflammation and Angiogenesis.

Chronic wounds that are difficult to heal pose a major challenge for clinicians and researchers. Currently, common treatment methods focus on isolating the wound from the outside world, relying on the tissue at the wound site to grow and heal unaided. Umbilical cord mesenchymal stem cell (MSC) exosomes can promote wound healing by enhancing new blood vessel growth at the wound site. Valproic acid (VPA) reduces the inflammatory response and acts on macrophages to accelerate wound closure. In this study, VPA was loaded into umbilical cord MSC exosomes to form a drug carrier exosome (VPA-EXO) with the aim of investigating the effect of VPA-EXO on wound healing. This study first isolated and obtained umbilical cord MSC exosomes, then added VPA to the exosomes and explored the ability of VPA-EXO to promote the proliferation and migration of human skin fibroblasts (HSFs) and human umbilical vein endothelial cells (HUVECs), as well as the ability to promote the angiogenesis of HUVECs, by using scratch, Transwell, and angiogenesis assays. An in vitro cell model was established and treated with VPA-EXO, and the expression levels of inflammation and pro-angiogenesis-related proteins and genes were examined using Western blot and qRT-PCR. The therapeutic effect of VPA-EXO on promoting wound healing in a whole skin wound model was investigated using image analysis of the wound site, H&E staining, and immunohistochemical staining experiments in a mouse wound model. The in vitro model showed that VPA-EXO effectively promoted the proliferation and migration of human skin fibroblast cells and human umbilical vein endothelial cells; significantly inhibited the expression of MMP-9, IL-1β, IL-8, TNF-α, and PG-E2; and promoted the expression of vascular endothelial growth factors. In the mouse wound model, VPA-EXO reduced inflammation at the wound site, accelerated wound healing, and significantly increased the collagen content of tissue at the wound site. As a complex with dual efficacy in simultaneously promoting tissue regeneration and inhibiting inflammation, VPA-EXO has potential applications in tissue wound healing and vascular regeneration. In future studies, we will further investigate the mechanism of action and application scenarios of drug-loaded exosome complexes in different types of wound healing and vascular regeneration.

Dual-layer nanofibrous PCL/gelatin membrane as a sealant barrier to prevent postoperative pancreatic leakage

Post-operative pancreatic leakage is a severe surgical complication that can cause internal bleeding, infections, multiple organ damage, and even death. To prevent pancreatic leakage and enhance the protection of the suture lining and tissue regeneration, a dual-layer nanofibrous membrane composed of synthetic polymer polycaprolactone (PCL) and biopolymer gelatin was developed. The fabrication of this dual-layer (PGI-PGO) membrane was achieved through the electrospinning technique, with the inner layer (PGI) containing 2% PCL (w/v) and 10% gelatin (w/v), and the outer layer (PGO) containing 10% PCL (w/v) and 10% gelatin (w/v) in mixing ratios of 2:1 and 1:1, respectively. Experimental results indicated that a higher gelatin content reduced fiber diameter enhanced the hydrophilicity of the PGI layer compared to the PGO layer, improved the membrane’s biodegradability, and increased its adhesive properties. In vitro biocompatibility assessments with L929 fibroblast cells showed enhanced cell proliferation in the PGI-PGO membrane. In vivo studies confirmed that the PGI-PGO membrane effectively protected the suture line without any instances of leakage and promoted wound healing within four weeks post-surgery. In conclusion, the nanofibrous PGI-PGO membrane demonstrates a promising therapeutic potential to prevent postoperative pancreatic leakage.

Molecular Mechanisms of Ozonized Nigella sativa Oil in Wound Repair: Albumin as Biomarker in Rat Model

Background: Wound healing is a complex physiological process that can be impaired in various conditions. Nigella sativa oil, rich in bioactive compounds like thymoquinone, has shown promise in promoting wound healing. Ozone therapy, through the generation of reactive oxygen species (ROS), has also been explored for its potential to accelerate wound repair. This study aimed to investigate the molecular mechanisms underlying the effects of ozonized Nigella sativa oil on wound healing, with a focus on albumin as a biomarker of tissue regeneration in a rat model. Methods: Full-thickness skin wounds were created on the backs of Sprague Dawley rats. The rats were randomly divided into four groups: a control group receiving no treatment, and three treatment groups receiving topical applications of ozonized Nigella sativa oil at different ozone concentrations (1400 mg/ml, 1800 mg/ml, and 2200 mg/ml) for 7 days. Wound healing was assessed by measuring wound closure rates and histological analysis. Albumin levels in wound tissue were quantified using immunohistochemistry. Additionally, the expression of key genes involved in wound healing, including growth factors, cytokines, and matrix metalloproteinases, was evaluated using quantitative real-time PCR. Results: Ozonized Nigella sativa oil significantly accelerated wound closure compared to the control group. Histological analysis revealed improved tissue regeneration and collagen deposition in the treated groups. Albumin levels were significantly elevated in the wound tissue of rats treated with ozonized Nigella sativa oil, particularly at the highest ozone concentration. Furthermore, the expression of growth factors (VEGF, TGF-β), pro-inflammatory cytokines (IL-1β, TNF-α), and matrix metalloproteinases (MMP-2, MMP-9) was modulated in a manner consistent with enhanced wound healing. Conclusion: Ozonized Nigella sativa oil promotes wound healing in a rat model through multiple molecular mechanisms, including the stimulation of albumin synthesis, growth factor expression, and controlled inflammation. These findings suggest that ozonized Nigella sativa oil may have therapeutic potential for enhancing wound repair in clinical settings.