Skin Wound Healing In Rats Research Articles

The Role of Mesenchymal Stem Cell Derived Exosomes versus Melatonin on Skin Wound Healing of Adult Male Albino Rats: Histological Study

The Role of Mesenchymal Stem Cell Derived Exosomes versus Melatonin on Skin Wound Healing of Adult Male Albino Rats: Histological Study

Therapeutic potential of cannabis for surgical wound healing in rats.

This study was conducted to evaluate the wound-healing activities of a Cannabis sativa L. plant extract and cannabidiol on incision wounds. An incision was created and sutured in rats under anaesthesia. Routine wound care procedures were applied for 10 days, followed by histological wound examinations. The cellular bioactivities of the hemp extract and CBD were assessed for MCP-1, EGF, BFGF, IL-8, and COL-1 using ELISA on the rat skin wound healing activity. A one-way ANOVA was used for the data analysis. The EGF values in the plasma were similar in the povidone-iodine, hemp seed oil, and hemp essential oil groups (P > 0.05). However, the EGF levels were lower in the CBD group compared to the other groups (P < 0.001, P < 0.005). The MCP-1 values in the hemp seed oil, hemp essential oil, and CBD were similar (P > 0.05), whereas povidone iodine exhibited lower MCP-1 levels compared to the other groups (P < 0.001, P < 0.005). It was determined that the plasma BFGF, IL-8, and COL 1 values of the groups were similar (P > 0.05). To our knowledge, this study is the first to evaluate the effects of CBD, seed oil, and hemp leaf extract on incision wound healing. It demonstrates that hemp extract holds greater potential benefits for wound healing compared to CBD.

Indole-3-carbinol loaded-nanocapsules modulated inflammatory and oxidative damages and increase skin wound healing in rats

This study evaluated the effects of topically applied hydrogels (HG) containing nanoencapsulated indol-3-carbinol (I3C) and its free form in a rat model of skin wounds. Formulations were topically applied twice a day for five days to the wounds. On days 1, 3, and 6, the wound area was measured to verify the % of regression. On the sixth day, the animals were euthanized for the analysis of the inflammatory and oxidative profile in wounds. The nanocapsules (NC) exhibited physicochemical characteristics compatible with this kind of suspension. After five hours of exposure to ultraviolet C, more than 78% of I3C content in the suspensions was still observed. The NC-I3C did not modify the physicochemical characteristics of HG when compared to the HG base. In the in vivo study, an increase in the size of the wound was observed on the 3rd experimental day, which was lower in the treated groups (mainly in HG-NC-I3C) compared to the control. On the 6th day, HG-I3C, HG-NC-B, and HG-NC-I3C showed lower regression of the wound compared to the control. Additionally, HG-NC-I3C exhibited an anti-inflammatory effect (as observed by decreased levels of interleukin-1B and myeloperoxidase), reduced oxidative damage (by decreased reactive species, lipid peroxidation, and protein carbonylation levels), and increased antioxidant defense (by improved catalase activity and vitamin C levels) compared to the control. The current study showed more satisfactory results in the HG-NC-I3C group than in the free form of I3C in decreasing acute inflammation and oxidative damage in wounds.

Accelerating γ-irradiated skin wound healing in rats by human amniotic membrane and/or chitosan

Accelerating γ-irradiated skin wound healing in rats by human amniotic membrane and/or chitosan

Astaxanthin Expedites the Healing of Acute Skin Wounds in Rats by Facilitating M2 Macrophage Polarization and Enhancing Collagen Secretion.

Facilitating the healing process of skin post-trauma is crucial for minimizing infection risks and reinstating normal tissue functionality. While past studies have established astaxanthin (ASX) as an effective compound in promoting wound healing, the precise mechanism of its action remains unclear. Consequently, the objective of this study was to explore the impact of ASX on the acute wound healing of rat skin by modulating macrophage polarization. Eighteen male SD rats were randomly assigned to control, dimethylsulfoxide (DMSO), and ASX groups. Acute skin wounds were induced in the rats, and the effects of different treatments on wound area and healing were assessed. Hematoxylin-eosin (H&E) staining was employed to detect histopathological changes in the skin, while Masson staining was utilized to observe collagen expression. Immunohistochemistry was conducted to identify clusters of differentiation (CD) 206 macrophages in the tissues. Furthermore, enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, IL-10, IL-4, and IL-13. The expression of inducible nitric oxide synthase (iNOS), arginase (Arg)-1, and mannose receptor C-type 1 (Mrc1) proteins in the injured skin of rats was assessed through Western blot analysis. On postoperative days 7 and 14, the ASX treatment demonstrated notable reductions in inflammatory cell infiltration and inflammatory cytokine expression when compared to the Control and DMSO groups. This was accompanied by evident improvements in the pathological changes in skin tissue, characterized by the regeneration of new epidermis, dermal repair, and increased thickness of granulation, contributing to enhanced scar formation. Furthermore, ASX therapy exhibited an upregulation in the expression levels of collagen I and collagen III, along with markers indicative of M2 macrophages. These findings collectively signify the accelerated progression of wound healing attributed to ASX intervention. In summary, these findings collectively indicate that ASX facilitates the healing of rat skin wounds by suppressing inflammatory responses and fostering M2 macrophage polarization. Consequently, ASX holds promise as a potentially effective drug for the treatment of skin wounds.

Novel garden cress-fish gelatin based ointment: Improvement of skin wound healing in rats through modulation of anti-inflammatory and antioxidant states

This study aimed to investigate the ability of aqueous extract of Lepidium sativum seeds (LSE) to improve the wound healing process in rat models. The gelatin, extracted from the skin of smooth-hound shark using citric acid, was used as a support material for ointment. Animals were divided into four groups of six rats each: an untreated control group, a control group treated with Moist Exposed Burn Ointment (MEBO), a treated group with gelatin gel, and a treated group with gelatin gel fortified with 20 mg/mL LSE. Phenolics profile analysis showed that the major compounds in LSE were catechin (125 μg/g) and quinic acid (105 μg/g). In vitro antioxidant tests showed that LSE has interesting activities to scavenge ABTS•+ radicals (IC50 = 0.22 mg/mL) and inhibit the oxidation of linoleic acid. A significant decline in the antioxidant enzymes activities and an increase in the level of thiobarbituric acid reactive substances (TBARS) and inflammatory markers was observed within the injured tissues of the untreated rats compared to rats treated with MEBO. Interestingly, when the wounded tissue was treated with gelatin gel a remarkable reversal of this trend occurred. Further, by enrichment of gelatin gel with LSE, the levels of CAT, GPx and SOD activities significantly increased by 35, 126, and 212 %, respectively, whereas the TBARS level was reduced by 31 %. These results were consistent with the wound contraction percentage and histological analysis, which suggest the potential effect of LSE-enriched gelatin gels to regenerate damaged tissues.

Histological Evaluation of Effect of Thymosin Beta 4 on Wound Healing of Skin

Skin wound healing is a normal biological process, achieved through four precisely and highly programmed phases: 1.hemostasis, 2.inflammation,3. proliferation, 4. remodeling. For a wound to heal successfully, Thymosin beta 4 (Tβ4) is a highly conserved, naturally occurring, water-soluble regenerative peptide that has biological activities of promoting angiogenesis, anti-inflammation, anti-apoptosis, and anti-fibrosis, and has many important functions in wound repair. This study aims to histologically examine the effect of systemic Thymosin beta 4 treatment with regard to skin wound healing in rats. A total number of 36 Western Albino rats with body weight (250-350 gm) and aging from(1-2 months) divided into two main groups each group was subdivided into 3 subgroups (6 rats in each) according to the healing period (1,3 and7 days). Full thickness wound of circular area 2 mm in depth was made on the dorsum of each rat with sterile biopsy punch of 5 mm diameter. The present study show role of Tβ4 in increase wound contraction, inflammatory cell and blood vessels proliferation at certain day of wound healing. Exogenous Tβ4 has bioactive role in wound healing when administrated systemically as it accelerate healing process at certain phases.

Preparation of recombinant mussel mucin Mfp-3P and its promotion of wound healing

To investigate the role of recombinant mussel mucin in wound healing, we aimed to prepare this mucin using Pichia pastoris as the host microbe. Our method involved constructing a genetically engineered strain of P. pastoris that expressed a fusion protein consisting of Mfp-3 and preCol-P peptide segments of mussel. After fermentation and purification, we obtained a pure recombinant mussel mucin product. We then conducted experiments to evaluate its effect at both the cellular and animal levels. At the cellular level, we examined its impact on the proliferation and migration of mouse fibroblast L929. At the animal level, we assessed its ability to promote wound healing after full-layer skin resection in rats. Our results showed that the recombinant mussel mucin protein has a content of 90.28% and a purity of 96.49%. The content of 3,4-dihydroxyphenylalanine (DOPA) was 0.73 wt%, and the endotoxin content was less than 0.5 EU/mg. Importantly, the recombinant mussel mucin protein significantly promoted both the migration and proliferation of mouse fibroblast, as well as the wound healing in rat skin. In conclusion, our findings demonstrate that recombinant mussel mucin has the potential to promote wound healing and can be considered a promising medical biomaterial.

Tissue Regeneration and Remodeling in Rat Models after Application of Hypericum perforatum L. Extract-Loaded Bigels.

The wound-healing effect of St. John's Wort (SJW) is mainly attributed to hyperforin (HP), but its low stability restricts its topical administration. This study investigates how "free" HP-rich SJW extract (incorporated into a bigel; B/SJW) and extract "protected" by nanostructured lipid carriers (also included in a biphasic semisolid; B/NLC-SJW) affect tissue regeneration in a rat skin excision wound model. Wound diameter, histological changes, and tissue gene expression levels of fibronectin (Fn), matrix metalloproteinase 8 (MMP8), and tumor necrosis factor-alpha (TNF-α) were employed to quantify the healing progress. A significant wound size reduction was achieved after applying both extract-containing semisolids, but after a 21-day application period, the smallest wound size was observed in the B/NLC-SJW-treated animals. However, the inflammatory response was affected more favorably by the bigel containing the "free" SJW extract, as evidenced by histological studies. Moreover, after the application of B/SJW, the expression of Fn, MMP8, and TNF-α was significantly higher than in the positive control. In conclusion, both bigel formulations exhibited beneficial effects on wound healing in rat skin, but B/SJW affected skin restoration processes in a comprehensive and more efficient way.

Association of a Skin Dressing Made With the Organic Part of Marine Sponges and Photobiomodulation on the Wound Healing in an Animal Model.

The present study aims to characterize and to evaluate the biological effects of a skin dressing manufactured with the organic part of the Chondrilla caribensis marine sponge (called spongin-like collagen (SC)) associated or not to photobiomodulation (PBM) on the skin wound healing of rats. Skin dressings were manufactured with SC and it was characterized using scanning electron microscopy (SEM) and a tensile assay. In order to evaluate its biological effects, an experimental model of cutaneous wounds was surgically performed. Eighteen rats were randomly distributed into three experimental groups: control group (CG): animals with skin wounds but without any treatment; marine collagen dressing group (DG): animals with skin wounds treated with marine collagen dressing; and the marine collagen dressing + PBM group (DPG): animals with skin wounds treated with marine collagen dressing and PBM. Histopathological, histomorphometric, and immunohistochemical evaluations (qualitative and semiquantitative) of COX2, TGFβ, FGF, and VEGF were done. SEM demonstrates that the marine collagen dressing presented pores and interconnected fibers and adequate mechanical strength. Furthermore, in the microscopic analysis, an incomplete reepithelialization and the presence of granulation tissue with inflammatory infiltrate were observed in all experimental groups. In addition, foreign body was identified in the DG and DPG. COX2, TGFβ, FGF, and VEGF immunostaining was observed predominantly in the wound area of all experimental groups, with a statistically significant difference for FGF immunostaining score of DPG in relation to CG. The marine collagen dressing presented adequate physical characteristics and its association with PBM presented favorable biological effects to the skin repair process.

Metformin lotion promotes scarless skin tissue formation through AMPK activation, TGF-β1 inhibition, and reduced myofibroblast numbers.

Scar tissue formation following skin wound healing is a challenging public health problem. Skin regeneration and preventing the formation of scar tissue by currently available commercial products are largely ineffective. This study aimed to test the efficacy of a novel topical metformin lotion (ML) in inhibiting scar tissue formation during skin wound healing in rats and to determine the mechanisms of action involved. A 6% ML was prepared in our laboratory. A skin wound healing model in rats was used. The wounded rats were divided into two groups and treated daily for 10 days as follows: Group 1 received a daily application of 50 mg of control lotion, or 0% ML (totaling 100 mg of lotion per rat), and Group 2 received a daily application of 50 mg of 6% ML (totaling 100 mg of 6% ML per rat). Blood samples from the heart of each rat were analyzed for inflammatory markers, HMGB1 and IL-1β, using ELISA, and immunological and histological analyses were performed on skin tissue sections. ML decreased levels of inflammatory markers HMGB1 and IL-1β in the serum of rats and inhibited the release of HMGB1 from cell nuclei into the skin tissue matrix. Additionally, ML demonstrated anti-fibrotic properties by enhancing AMPK activity, decreasing the expression of TGF-β1, reducing the number of myofibroblasts, decreasing the production of collagen III, and increasing the expression of collagen I. ML promotes the regeneration of high-quality skin during wound healing by reducing scar tissue formation. This effect is mediated through the activation of AMPK, inhibition of TGF-β1, and a decrease in the number of myofibroblasts.

The Effect of Age on the Regenerative Potential of Adipose Stem-cell-derived Apoptotic Extracellular Vesicles in Rat Skin Wound Healing.

Introduction: Skin, being the body's largest organ, is susceptible to injuries. Despite the adoption of common treatments such as debridement, wound dressing, and infection control measures for skin injuries, the outcomes remain unsatisfactory, especially in diabetic patients or elderly patients. The use of adipose stem cell-derived apoptotic extracellular vesicles (apoEVs-ASCs) has been shown great therapeutic potential in wound repair. The effect of the donor age on the biological properties and functions of apoEVs-ASCs has not been reported. Methods: In this study, we isolated apoEVs-ASCs from young and aged rats. Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) were applied for the characteristics of apoEVs-ASCs. For aged and young apoEVs-ASCs groups, the proliferative and migration abilities in vitro, and wound healing function in vivo were contrastively evaluated and quantified for statistical analysis. Results: Our results showed that both young and aged apoEVs-ASCs induced skin healing and reduced scar formation. In addition, young apoEVs-ASCs had significantly higher proliferation, migration of fibroblasts and endothelial cells, and increased neo-angiogenesis ability, when compared with that of aged apoEVs-ASCs. Conclusion: Young apoEVs-ASCs should be employed for wound repair, which is associated with its superior promoting effect on wound healing.

Contribution of Probiotics to the Effect of Platelet-Rich Plasma in Diabetic Rat Skin Wound Healing

Contribution of Probiotics to the Effect of Platelet-Rich Plasma in Diabetic Rat Skin Wound Healing

Effect of Honey/PVA Hydrogel Loaded by Erythromycin on Full-Thickness Skin Wound Healing in Rats; Stereological Study

Background: Skin wounds are a significant public health risk, and treatment of wound remains a challenging clinical problem for medical teams and researchers.Materials and Methods: In the present study, we aimed to investigate the healing effects of honey/polyvinyl alcohol (PVA) hydrogel loaded with erythromycin  as wound dressing on skin wounds in rats, based on histological studies. In this study, 60 male Wistar rats, with a 1.5 ×1.5 cm2 diameter full-thickness wounds on the backs were divided into four groups: honey/PVA with the erythromycin hydrogel group, honey group, PVA group, and the control group, with no treatment. Skin biopsies were prepared at days 4, 7, and 14 for microscopic analyses. The stereological analysis, including the mean area of the wound, length of vessels, numerical density of fibroblast, macrophage, basal cell and volume of the epidermis, dermis, and fibrous tissue were performed. Result: Wounds area in the honey/PVA hydrogel with the erythromycin group were significantly (P&lt;0.05) smaller than in the other group. The numerical density of fibroblast, macrophage, basal cell and volume of the epidermis in the honey/PVA hydrogel with the erythromycin group were significantly higher than other groups.Conclusion: According to our results, honey/PVA hydrogel with erythromycin may promote early wound healing and has a positive influence on fibroblast proliferation and re-epithelialization, and its administration is recommended after further validation of clinical data. [GMJ. 2019;8:e1362]

Shikonin potentiates skin wound healing in Sprague-Dawley rats by stimulating fibroblast and endothelial cell proliferation and angiogenesis.

Shikonin, a major component of Lithospermum erythrorhizon, exerts anti-inflammatory and antibacterial effects and expedites wound healing. This study aims to evaluate the anti-inflammatory and antioxidant activities of shikonin in a Sprague-Dawley rat model and cell models using fibroblast and endothelial cells. The impact of shikonin on the activity of endothelial cells and fibroblasts was examined by cell counting kit 8 and wound-healing assays. A diabetic rat model was constructed, followed by wound creation for treatment with shikonin. Hematoxylin-eosin staining was used to assess pathological changes, and Masson's trichrome method to detect collagen deposition. Immunohistochemistry using antibodies against proliferating cell nuclear antigen and CD31 was conducted to detect proliferation and vascular density. Enzyme-linked immunosorbent assay and immunohistochemistry were carried out to assess pro-inflammatory and anti-inflammatory factor concentrations. Western blot and immunofluorescence were implemented to analyze oxidative stress-related protein expression. Shikonin induced the activity of both fibroblasts and endothelial cells. Shikonin treatment contributed to facilitated wound healing and higher healing rates in rats. It also resulted in faster lesion debulking in tissues, reduced inflammatory infiltration, increased collagen deposition, and enhanced angiogenesis. Detection of markers at the wounds showed that shikonin accelerated cell proliferation, enhanced tissue remodeling, and inhibited oxidative stress. Shikonin stimulates the proliferation and migration of fibroblasts and endothelial cells to promote angiogenesis and tissue remodeling, resulting in faster wound healing.

Effects of common centaury (Centaurium erythraea) oil and laurel (Laurus nobilis) seed oil on full-thickness excisional skin wound healing in rats

The aim was to investigate the effects of common centaury (Centaurium erythraea) oil and laurel (Laurus nobilis) seed oil in a full-thickness excisional skin wound model in rats. In the study, 18 adult male Wistar rats were divided into three groups (n=6) as control (CO) group, common centaury oil (CCO) group, and laurel seed oil (LSO) group. Under general anesthesia, a full-thickness excisional wound (2.25 cm²) was created on the caudal of the interscapular region on the back of the rats. Treatments were applied topically once a day in all groups. Wound area measurements revealed that the use of CCO accelerated wound healing, while the use of LSO has disturbed. In the histopathological results, blood vessel formation, fiber synthesis, granulation and mononuclear cells in the wounds were higher in the CCO group than the other groups, and higher in the LSO group than the CO group. Biochemical results revealed differences between groups in TP, GLU and UREA values (p &lt; 0.05). As a result of this study, it was determined that the topical use of common centaury oil accelerated wound healing, while laurel seed oil adversely affected wound healing in the experimental excisional full-thickness skin wound model in rats.

Paeonol accelerates skin wound healing by regulating macrophage polarization and inflammation in diabetic rats.

Diabetic ulcer is usually seen in people with uncontrolled blood sugar. Reportedly, many factors such as impaired glucose metabolism, and macrovascular and microvascular diseases caused angiogenesis disorders and delayed the healing of diabetic ulcers, thus affecting the body's metabolism, nutrition, and immune function. This study aimed to explore the effect of paeonol on skin wound healing in diabetic rats and the related mechanism. A rat model of diabetic ulcer was established. High glucose-treated mouse skin fibroblasts were co-cultured with M1 or M2-polarized macrophages treated with or without paeonol. H&E and Masson staining were used to reveal inflammatory cell infiltration and collagen deposition, respectively. Immunohistochemistry visualized the expression of Ki67, CD31, and vascular endothelial growth factor (VEGF). Western blot was used to detect interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-4, IL-10, CD31, VEGFA, and collagen I/III. The expression of iNOS and arginase 1 was revealed by immunofluorescence staining. Paeonol treatment augmented collagen deposition and the expression of Ki67, CD31, VEGF, and macrophage M2 polarization markers (IL-4 and IL-10) and reduced wound area, inflammatory cell infiltration, and macrophage M1 polarization markers (IL-1β and TNF-α) in the ulcerated area. In vitro, paeonol treatment promoted M2-polarization and repressed M1-polarization in macrophages, thereby improving the repair of cell damage induced by high glucose. Paeonol accelerates the healing of diabetic ulcers by promoting M2 macrophage polarization and inhibiting M1 macrophage polarization.

Photocuring and Gelatin-Based Antibacterial Hydrogel for Skin Care.

The development of moisturizing, antibacterial, and biocompatible multifunctional hydrogels is essential to protect skin and promote skin defects recovery. Gelatin has admired potential to be applied for skin care as a hydrogel in virtue of its hydrophilic biocompatible and biodegradable properties. In this study, triclosan-grafted gelatin and photo-cross-linkable methacrylated gelatin were synthesized and then combined to construct the semi-interpenetrating network and antibacterial hydrogels with the aid of a visible blue light. The antimicrobial test demonstrated that the resulting hydrogel obtained excellent inactivation capacity against E. coli, S. aureus, T. rubrum, and C. albicans with sterilizing rates of 99.998%, 99.998%, 99.19%, and 99.64%, respectively. In addition, the cytotoxicity, hemolysis, skin irritation, and rat skin wound healing experiments proved the good biocompatibility of the hydrogel. Therefore, this investigation sheds light on the development of multifunctional hydrogels in skin care.

A frog peptide provides new strategies for the intervention against skin wound healing

BackgroundAmphibian derived pro-healing peptides as molecular probes might provide a promising strategy for development of drug candidates and elucidation of cellular and molecular mechanisms of skin wound healing. A novel skin amphibian peptide, OA-RD17, was tested for modulation of cellular and molecular mechanisms associated with skin wound healing.MethodsCell scratch, cell proliferation, trans-well, and colony formation assays were used to explore the pro-healing ability of peptide OA-RD17 and microRNA-632 (miR-632). Then, the therapeutic effects of OA-RD17 and miR-632 were assessed in mice, diabetic patient ex vivo skin wounds and SD rats. Moreover, hematoxylin and eosin (H&E), enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and immunofluorescence staining were performed to detect skin wound tissue regeneration, inflammatory factors expression, and macrophage polarization. Finally, RNA sequencing, molecular docking, co-localization, dual luciferase reporter, real-time quantitative reverse transcription PCR (RT-qPCR), and Western blotting were used to explore the mechanism of OA-RD17 and miR-632 on facilitating skin wound healing.ResultsThe non-toxic peptide (OA-RD17) promoted macrophage proliferation and migration by activating MAPK and suppressed inflammation by inhibiting NF-κB. In keratinocytes, OA-RD17 inhibited excessive inflammation, and activated MAPK via the Toll-like receptor 4 (TLR4) to promote proliferation and migration, as well as up-regulate the expression of miR-632, which targeted GSK3β to activate Wnt/β-catenin to boost proliferation and migration in a positive feedback manner. Notably, OA-RD17 promoted transition from the inflammatory to proliferative stage, accelerated epidermal and granulation regeneration, and exhibited therapeutic effects on mouse and diabetic patient ex vivo skin wounds. MiR-632 activated Wnt/β-catenin to promote full-thickness skin wound healing in rats.ConclusionsOA-RD17 exhibited promising therapeutic effects on mice (full-thickness, deep second-degree burns), and ex vivo skin wounds in diabetic patients by regulating macrophages proliferation, migration, and polarization (MAPK, NF-κB), and keratinocytes proliferation and migration (TLR4/MAPK/miR-632/Wnt/β-catenin molecular axis). Moreover, miR-632 also activated Wnt/β-catenin to promote full-thickness skin wound healing in rats. Notably, our results indicate that OA-RD17 and miR-632 are promising pro-healing drug candidates.Graphical

Dead but functional liquid nitrogen‐treated umbilical cord mesenchymal stem cells accelerate full‐thickness skin wound healing

AbstractBackgroundThe direct application of umbilical cord‐derived mesenchymal stem cells (UCMSCs) for promoting skin wound healing and regeneration is challenging due to strict maintenance requirements and unpredictable differentiation results.MethodsWe developed dead but functional liquid nitrogen‐treated UCMSCs (LNT‐MSCs) by rapidly immersing live UCMSCs (live‐MSCs) in liquid nitrogen.ResultsThe LNT‐MSCs maintained similar cellular structures and surface markers to those of live‐MSCs. We evaluated the therapeutic effects of both live‐MSCs and LNT‐MSCs on full‐thickness skin wound healing in rats. Our results showed that the LNT‐MSCs accelerated wound closure by enhancing the proliferation and migration of skin cells, promoting angiogenesis, and inducing a favourable macrophage phenotype shift. The regenerative healing effect of LNT‐MSCs was comparable to that of live‐MSCs, making them a potential alternative strategy for accelerating wound closure that avoids unpredictable differentiation results and creates a ready‐to‐use cell bank for clinical applications.