Full-thickness Skin Wounds Research Articles

Identification of IGF2 promotes skin wound healing by co-expression analysis.

Oral mucosa is an ideal model for studying scarless wound healing. Researchers have shown that the key factors which promote scarless wound healing already exist in basal state of oral mucosa. Thus, to identify the other potential factors in basal state of oral mucosa will benefit to skin wound healing. In this study, we identified eight gene modules enriched in wound healing stages of human skin and oral mucosa through co-expression analysis, among which the module M8 was only module enriched in basal state of oral mucosa, indicating that the genes in module M8 may have key factors mediating scarless wound healing. Through bioinformatic analysis of genes in module M8, we found IGF2 may be the key factor mediating scarless wound healing of oral mucosa. Then, we purified IGF2 protein by prokaryotic expression, and we found that IGF2 could promote the proliferation and migration of HaCaT cells. Moreover, IGF2 promoted wound re-epithelialization and accelerated wound healing in a full-thickness skin wound model. Our findings identified IGF2 as a factor to promote skin wound healing which provide a potential target for wound healing therapy in clinic.

The effect of combining humic and fulvic acids poultice on wound healing in male rats

Abstract Background: Finding new compounds to accelerate wound healing is critical today. Humic substances or fulvic acid each have anti-inflammatory properties. Aims and Objectives: The purpose of this study is to determine the effects of poultice 0.5% containing humic and fulvic acids on wound healing in male rats. Materials and Methods: An animal model was arranged by making a full-thickness skin wound was created in each rat. Animals were randomly divided into control, sham, and treatment groups. To investigate the effect of humic and fulvic acids combining poultice, the wound area and histological analyses of the number of inflammatory cells, fibroblasts, and angiogenesis were evaluated for 21 days. Results: The animals in the treated group showed higher wound healing percentage, angiogenesis, and fibroblast distribution compared with the control (P < 0.001). Moreover, the topical administration of humic and fulvic acids 0.5% poultice decreased the mean number of inflammatory cells significantly than the other groups (P < 0.001). Conclusion: The topical administration of a poultice containing humic and fulvic acid accelerated wound healing by increasing angiogenesis and fibroblast and reducing inflammatory cell distribution in a rat model.

Biodegradable all-natural hydrogel–mesh composite for wet tissues adhesion and infected wound healing

The application of meshes in surgery is severely limited by complications associated with the non-absorbable nature, the lack of bioactivities, and the need of sutures and/or staples to fix meshes on tissues. In this contribution, a self-adhesive hydrogel-mesh composite (HMC) with biodegradability and multiple bioactivities was developed to address these issues and meet the clinical requirements. In this HMC system, GelMA hydrogel network was first macrotopological entangled with the fibers of a natural small intestinal submucosa (SIS) meshes, and then strengthened by soaking in a multi-functional H-bond provider (i.e., tannic acid, TA) solution to form the G/SIS-TA composite. The pyrogallol groups of the TA molecules endow G/SIS-TA with excellent wet adhesiveness (shear strength: ∼60 kPa), antioxidant, and antibacterial ability. The G/SIS-TA was also found to exhibit excellent biodegradability, biocompatibility, and immunoregulatory activity. The G/SIS-TA significantly decrease the bacterial burden in a mouse peritonitis infection model and promote the healing of infected full-thickness rat skin wounds in vivo. This work not only reports a novel SIS-based HMC which was efficient in treating infected wounds, but also offers an innovative strategy of the development of self-adhesive bio-patch for various biomedical applications.

Hyaluronic acid hydrogels with excellent self-healing capacity and photo-enhanced mechanical properties for wound healing

A continuously stable moist healing environment is immensely beneficial for wound healing, which can be availably achieved by providing an in situ hydrogel with enough strength resembling skin tissue and self-healing ability. Herein, through a dual-crosslinking strategy, hyaluronic acid-based hydrogels with excellent self-healing capacity and enhanced mechanical properties are fabricated via the acylhydrazone linkages and subsequent photocrosslinking based on hydrazide-modified sodium hyaluronate and aldehyde-modified maleic sodium hyaluronate. The hydrogels demonstrate the fast gelation process (< 1 min), the controlled swelling behaviors, and the good biocompatibility. Notably, they possess enhanced mechanical strength similar to the human dermis (∼ 2.2 kPa). Also, they can self-heal rapidly with a self-healing efficiency of ∼90 % at 6 h. Based on this, the hyaluronic acid-based hydrogels, without any biological factors involved, can facilitate the full-thickness skin wound reconstruction process by accelerating the three phases of the wound repair, including reducing wound inflammation in the inflammatory phase, promoting angiogenesis in the proliferative phase, and promoting the deposition and reconstruction of collagen in the remodeling phase. The produced hyaluronic acid hydrogel can serve as an ideal candidate for wound healing.

Multifunctional fish-skin collagen-based hydrogel sealant with dual-dynamic-bond cross-linked for rapid hemostasis and accelerated wound healing

Collagen (COL) is the most widespread functional protein. Designing and developing dual-dynamic-bond cross-linked COL adhesive hydrogel sealants with multifunctional is highly advantageous for achieving a superior wound closure effect and hemostasis. In this study, we developed hybrid hydrogels consisting of fish-skin COL, oxidized sodium alginate (OSA), borax and polyvinyl alcohol (PVA) to enhance full-thickness wound healing. The hydrogels were furnished with first-rate self-healing capabilities through the dual-dynamic-bond cross-linking of dynamic Schiff base bonds (COL-OSA) and diol boric acid bonds (OSA-borax) with reversible breakage and re-formation. Moreover, the incorporation of PVA stimulated the formation of hydrogen bonds in the system, bolstering the stability of the hydrogel framework. The prepared hydrogel manifests self-healing, injectability, multifunctional adhesiveness and biodegradability. In vivo assessment of the hemostatic capacity of COSP20 hydrogel was superior to gauze both in the mice liver injury model and mice tail amputation model. In addition, a full-thickness skin wound model in mice revealed that the COSP20 hydrogel facilitated faster wound closure by accelerating reepithelialization, COL deposition and angiogenesis. These findings illustrate the potential of hybrid fish-skin COL-based hydrogels to enhance wound healing and promote rapid tissue repair, and provide new possibilities for the effective utilization of marine fishery resources.

Proteoglycan 4 (PRG4) treatment improves skin wound healing in a porcine model.

Proteoglycan 4 (PRG4) is a boundary lubricant originally identified in articular cartilage and has been since shown to have immunomodulation and antifibrotic properties. Previously, we have demonstrated that recombinant human (rh)PRG4 treatment accelerates auricular cartilage injury closure through an inhibition of the fibrotic response, and promotion of tissue regeneration in mice. The purpose of the current study was to examine the effects of rhPRG4 treatment (vs. a DMSO carried control) on full-thickness skin wound healing in a preclinical porcine model. Our findings suggest that while rhPRG4 did not significantly accelerate nor impede full-thickness skin wound closure, it did improve repair quality by decreasing molecular markers of fibrosis and increasing re-vascularization. We also demonstrated that rhPRG4 treatment increased dermal adipose tissue during the healing process specifically by retaining adipocytes in the wound area but did not inhibit lipolysis. Overall, the results of the current study have demonstrated that rhPRG4 acts as antifibrotic agent and regulates dermal adipose tissue during the healing processes resulting in a tissue with a trajectory that more resembles the native skin vs. a fibrotic patch. This study provides strong rationale to examine if rhPRG4 can improve regeneration in human wounds.

One–step synthesis of silver nanoparticles by lignocellulose nanofibrils to obtain antimicrobial hydrogels with accelerated wound healing

Lignin–containing cellulose nanofibrils (LCNF) have attracted extensive attention in the field of antibacterial due to the properties both of lignin and nanofibrils. The evenly distributed nano–lignin in LCNF can reduce Ag+, and the fiber network structure of nanofibrils may prevent the sedimentation of silver nanoparticles (AgNPs), which makes LCNF promising candidates for one–step preparation and deposition of AgNPs. Herein, carboxylated lignocellulose nanofibrils (CLCNF) with high stability were used to initiate the redox reaction. AgNPs (∼10.45 nm) were successfully prepared and homogeneously anchored onto CLCNF (Ag–L NPs–CLCNF). After compositing with polyvinyl alcohol (PVA) and tetracycline hydrochloride (TH), Ag–L NPs–CLCNF constructed a reversible redox quinone/catechol chemistry, imparting hydrogels with long–lasting reproducible adhesion and antimicrobial activity. Moreover, the incorporation of Ag–L NPs–CLCNF significantly improved the tensile strength (30.87 kPa), compressive strength (368.11 kPa) and thermal stability of the hydrogels, and that the Ag–L NPs–CLCNF hydrogel were self–healing. Importantly, the hydrogel containing Ag–L NPs–CLCNF can realize the controlled delivery of TH, giving it excellent antibacterial activity with accompanied good biocompatibility and significantly promoting full–thickness skin wound healing. This work offers a novel idea for preparing antibacterial hydrogels from lignocellulosic nanofibrils and the hydrogels have great application prospects in wound dressing.

The effects of a synthetic epidermis spray on secondary intention wound healing in adult horses.

To evaluate secondary intention wound healing in the horse's limbs when treated with the synthetic epidermis spray (Novacika®, Cohesive S.A.S, France) or with a standard bandaging technique. Six Standardbred mares were included in the study. Four 2.5 x 2.5 cm full-thickness skin wounds were created on each thoracic limb. Two wounds were located on the dorsoproximal aspect of the cannon bone and the other two at the dorsoproximal aspect of the fetlock. Six hours after creation, wounds were randomly treated with synthetic epidermis spray or standard bandaging. The wounds were assessed every 4 days by gross visual assessment and using a 3D imaging camera. Analysis was performed with a 3D imaging application. Out of 46 wounds, 22 showed exuberant granulation tissue and were part of the standard bandaging group. Whether the wounds were treated with synthetic epidermis spray or standard bandaging, the time for healing was the same. The synthetic epidermis spray studied in this model has allowed healing without the production of exuberant granulation tissue but did not reduce the median wound healing time compared to a standard bandaging technique. The synthetic epidermis spray is potentially an interesting alternative for the management of secondary intention wound healing of superficial and non-infected distal limb wounds in adult horses on economical and practical aspects. However, all statistical inference (p-values especially) must be interpreted with caution, given the size of the sample.

Extracellular matrix-mimetic immunomodulatory fibrous scaffold based on a peony stamens polysaccharide for accelerated wound healing

Re-establishment of the extracellular matrix (ECM) in wound tissue is critical for activating endogenous tissue repair. In this study, we designed an ECM-like scaffold material using plant polysaccharides and assessed its efficacy through in vitro and in vivo experiments. The scaffold accelerates wound healing by regulating inflammatory responses and accelerating tissue regeneration. Briefly, we isolated two polysaccharides of varying molecular weights from peony stamens. One of the polysaccharides exhibits potent immunomodulatory and tissue regeneration activities. We further prepared electrospinning materials containing this polysaccharide. In vitro investigations have demonstrated the polysaccharide's ability to modulate immune responses by targeting TLR receptors. In vivo experiments utilizing a scaffold composed of this polysaccharide showed accelerated healing of full-thickness skin wounds in mice, promoting rapid tissue regeneration. In conclusion, our study shows that this scaffold can mobilize the endogenous regenerative capacity of tissues to accelerate repair by mimicking the characteristics of ECM. The overall study has implications for the design of new, effective, and safer tissue regeneration strategies.

Compound Microalgae-Type Biofunctional Hydrogel for Wound Repair during Full-Thickness Skin Injuries.

A dual biofunctional hydrogel (HQCS-SP) wound dressing, offering antibacterial properties and a biological response, was innovatively designed and developed to repair full-layer skin defects. The HQCS-SP hydrogel creates an artificial matrix that facilitates cell recruitment, extracellular matrix deposition, exhibiting exceptional tissue affinity, robust self-healing, effective hemostatic capabilities and accelerates wound healing. It is synthesized by crosslinking modified chitosan (HQCS) with spirulina protein (SP) and Fe3+. The HQCS provides antibacterial, antioxidant, good tissue affinity and excellent hemostasis performance. The incorporation of SP not only reinforces the antioxidant, antibacterial, anti-inflammatory, and pro-angiogenesis effects but also participates in the regulation of signal pathways and promotes wound healing. Therefore, this study offers a new visual angle for the design of advanced functional trauma dressings with great application potential in the bio-medical field.

Comparative evaluation of two different xenogenic acellular matrices on full-thickness skin wound healing.

The purpose of the study was to compare the healing potential of bubaline small intestinal matrix (bSIM) and fish swim bladder matrix (FSBM) on full-thickness skin wounds in rabbits. Four full-thickness skin wounds (each 20×20mm) were created on the dorsum of 18 rabbits that were divided into three groups based on treatment: untreated sham control (I), implanted with double layers of bSIM (II) and implanted with double layers of FSBM (III). Macroscopic, immunologic and histologic observations were made to evaluate wound healing. Gross healing progression in the bSIM and FSBM groups showed significantly (p<0.05) less wound contraction compared with the sham group. The IgG concentration in rabbit sera was significantly (p<0.05) lower in the FSBM group compared with the bSIM group by enzyme-linked immunosorbent assay. The stimulation index of peripheral blood lymphocytes was significantly (p<0.05) lower in the FSBM group compared with the bSIM group by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Implantation of FSBM resulted in improved re-epithelialisation, neovascularisation and fibroplasia. The FSBM is a more effective dermal substitute when compared with the bSIM for full-thickness skin wound repair in rabbit.

A novel sprayable thermosensitive hydrogel containing a sulfobutylether-β-cyclodextrin/glabridin inclusion complex promotes wound healing

This study concentrated on developing a novel sprayable hydrogel by the combination of a thermosensitive hydrogel (Pluronic F-127, PF-127) and an inclusion complex of glabridin (GLD) and sulfobutylether-β-cyclodextrin (SBE-β-CD). GLD was encapsulated into SBE-β-CD by the freeze-drying method. The successful encapsulation of the inclusion complex was verified by Fourier transform infrared (FT-IR), X-ray diffractometer (XRD), scanning electron microscope (SEM), and nuclear magnetic resonance spectroscopy (NMR). The prepared GLD/SBE-β-CD inclusion complex exhibited 93.24%～96.46% encapsulation efficiency and 11.24%～11.93% loading capacity, and GLD/SBE-β-CD showed excellent biocompatibility on human vascular endothelial cells (HUVECs) and erythrocytes. GLD/SBE-β-CD inclusion complex exerts higher antioxidant and antibacterial activity than GLD alone. The GLD/SBE-β-CD inclusion complex was well dispersed within 20% PF-127 solution to form the PF-127/GLD/SBE-β-CD hydrogel. Introducing the inclusion complex into the PF-127 hydrogel did not influence its loose and porous structure, while PF-127/GLD/SBE-β-CD hydrogel demonstrated controlled GLD release in a sustained manner. The full-thickness skin wound model showed that the PF-127/GLD/SBE-β-CD hydrogel accelerated the healing of traumatic skin defects. In one aspect, the porous and biocompatible structure of the hydrogel provides favorable conditions for skin cell adhesion and proliferation. In another respect, GLD in therapeutic hydrogel markedly promotes the angiogenesis of endothelial cells, and the migration of keratinocytes. It also presents excellent antibacterial properties in wound surface. Taken together, this work established a novel sprayable hydrogel (PF-127/GLD/SBE-β-CD) and proved that it is an effective strategy for traumatic wound healing.

Exosomes from adipose-derived stem cells activate sebocytes through the PI3K/AKT/SREBP-1 pathway to accelerate wound healing

Sebocyte regeneration after injury is considered a key element of functional skin repair. Exosomes from adipose-derived stem cells (ADSCs-EXO) accelerate wound healing by promoting the proliferation of fibroblasts. However, the effects of ADSCs-EXO on sebocytes are largely unknown. In this study, the effects of ADSCs-EXO on sebocyte proliferation and migration were evaluated. The levels of phosphorylated AKT (p-AKT), AKT, sterol regulatory-element binding protein (SREBP), and perilipin-1 (PLIN-1) were detected with immunofluorescence, quantitative PCR, and western blot analysis. RNA-Seq was used to analyze the differential gene expression between the ADSCs-EXO group and the control group under anaerobic conditions. Lipogenesis was assessed with Nile red staining. In animal studies, full-thickness skin wounds in BALB/c mice were treated with gelatin methacrylate (GelMA) hydrogel-loaded sebocytes alone or in combination with ADSCs-EXO. Histopathological assessments of the wound tissues were performed Masson Trichrome staining, Immunohistochemical staining and so on. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway blocker LY294002 inhibited the effects of ADSCs-EXO on p-AKT and sebocytes proliferation. ADSCs-EXO also regulated the expression of SREBP-1 and PLIN-1 through the PI3K/AKT pathway in an oxygen level-dependent manner. In BALB/c mice, ADSCs-EXO accelerated sebocyte-assisted wound healing and regeneration. These in vitro and in vivo results supported that ADSCs-EXO can promote the regeneration of fully functional skin after injury through the PI3K/AKT-dependent activation of sebocytes.Graphical abstract

Egg White Peptides Accelerating the Wound Healing Process Through Modulating the PI3K-AKT Pathway: A Joint Analysis of Transcriptomic and Proteomic.

Wound healing is a multiphase process with a complex repair mechanism; trauma-repairing products with safety and high efficiency have a great market demand. Egg white peptides (EWP) have various physiological regulatory functions and have been proven efficient in ameliorating skin damage. However, their underlying regulation mechanism has not been revealed. This study further evaluated the EWP ameliorating mechanism by conducting a full-thickness skin wound model. Results demonstrated that EWP administration significantly inhibited the expression of pro-inflammatory and shortened the inflammatory phase. Besides, EWP can accelerate the secretion of growth factors (PDGF, VEGF, and TGF-β1) in skin tissue, significantly increasing the regeneration of granulation tissue and endothelium in the proliferation phase, thereby promoting wound healing. After 400 mg/kg EWP interventions for 13 days postoperation, the wound healing rate reached 90%. The combination of transcriptomic and proteomic analyses demonstrated the ameliorating efficiency effects of EWP on wound healing. EWP mainly participates in the functional network with the PI3K-AKT signaling pathway as the core to accelerate wound healing. These findings suggest a promising EWP-based strategy for accelerating wound healing.

All-in-One Self-Powered Microneedle Device for Accelerating Infected Diabetic Wound Repair.

Diabetic wound healing remains a significant clinical challenge due to the complex microenvironment and attenuated endogenous electric field. Herein, a novel all-in-one self-powered microneedle device (termed TZ@mMN-TENG) is developed by combining the multifunctional microneedle carried tannin@ZnO microparticles (TZ@mMN) with the self-powered triboelectric nanogenerator (TENG). In addition to the delivery of tannin and Zn2+, TZ@mMN also effectively conducts electrical stimulation (ES) to infected diabetic wounds. As a self-powered device, the TENG can convert biomechanical motion into exogenous ES to accelerate the infected diabetic wound healing. In vitro experiment demonstrated that TZ@mMN shows excellent conductive, high antioxidant ability, and effective antibacterial properties against both Staphylococcus aureus and Escherichia coli (>99% antibacterial rates). Besides, the TZ@mMN-TENG can effectively promote cell proliferation and migration. In the diabetic rat full-thickness skin wound model infected with Staphylococcus aureus, the TZ@mMN-TENG can eliminate bacteria, accelerate epidermal growth (regenerative epidermis: ≈303.3 ± 19.1µm), enhance collagen deposition, inhibit inflammation (lower TNF-α and IL-6 expression), and promote angiogenesis (higher CD31 and VEGF expression) to accelerate infected wound repair. Overall, the TZ@mMN-TENG provides a promising strategy for clinical application in diabetic wound repair.

An Asymmetric Natural Nanofiber with Rapid Temperature Responsive Detachability Inspired by Andrias davidianus for Full-Thickness Skin Wound Healing

An Asymmetric Natural Nanofiber with Rapid Temperature Responsive Detachability Inspired by Andrias davidianus for Full-Thickness Skin Wound Healing

The direct binding of bioactive peptide Andersonin-W1 to TLR4 expedites the healing of diabetic skin wounds

BackgroundChronic nonhealing wounds remain a considerable challenge in clinical treatment due to excessive inflammation and impeded reepithelialization and angiogenesis. Therefore, the discovery of novel prohealing agents for chronic skin wounds are urgent and important. Amphibian-derived prohealing peptides, especially immunomodulatory peptides, provide a promising strategy for the treatment of chronic skin trauma. However, the mechanism of immunomodulatory peptides accelerating the skin wound healing remains poorly understood.MethodsThe prohealing ability of peptide Andersonin-W1 (AW1) was assessed by cell scratch, cell proliferation, transwell, and tube formation. Next, full-thickness, deep second-degree burns and diabetic full-thickness skin wounds in mice were performed to detect the therapeutic effects of AW1. Moreover, the tissue regeneration and expression of inflammatory cytokines were evaluated by hematoxylin and eosin (H&E), enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry staining. Molecular docking, colocalization, and western blotting were used to explore the mechanism of AW1 in promoting wound healing.ResultsWe provide solid evidence to display excellent prohealing effects of AW1, identified as a short antimicrobial peptide in our previous report. At relative low concentration of nM, AW1 promoted the proliferation, migration, and scratch repair of keratinocyte, macrophage proliferation, and tube formation of HUVEC. AW1 also facilitated reepithelialization, granulation regeneration, and angiogenesis, thus significantly boosting the healing of full-thickness, deep second-degree burns and diabetic skin wounds in mice. Mechanistically, in macrophages, AW1 directly bound to Toll-like receptor 4 (TLR4) in the extracellular region and regulated the downstream nuclear factor‐κB (NF-κB) signaling pathway to facilitate the inflammatory factor secretion and suppress excessive inflammation induced by lipopolysaccharide (LPS). Moreover, AW1 regulated macrophage polarization to promote the transition from the inflammatory to the proliferative phase and then facilitated reepithelialization, granulation regeneration, and angiogenesis, thus exhibiting excellent therapeutic effects on diabetic skin wounds.ConclusionsAW1 modulates inflammation and the wound healing process by the TLR4/NF-κB molecular axis, thus facilitating reepithelialization, granulation regeneration, and angiogenesis. These findings not only provided a promising multifunctional prohealing drug candidate for chronic nonhealing skin wounds but also highlighted the unique roles of “small” peptides in the elucidation of “big” human disease mechanisms.Graphical

Wound recovery efficacy of retinol based-micellar formulations in an organotypic skin wound model

Impairment of the skin's structural integrity initially results in acute wounds which can become chronic if timely wound closure is not achieved. Chronic wounds (CWs) affect more than 1% of the global population with increasing cases of this condition due to the ageing population. Current wound management relies on debridement, hyperbaric oxygen, antibiotics, and wound dressings, which lack early intervention and specificity. Herein, antibiotics-free retinol-based micellar formulations (RMF) were made and their wound healing efficacy were investigated in vitro. Five different formulations with retinol contents of 0.3% and 1% against a placebo were topically applied to an organotypic full-thickness skin wound model (FT-SWM, MatTek®) with a 3 mm punch wound, and maintained in an incubator for 6 days. The histological analysis of the FT-SWM was conducted at depths of 60 µm and 80 µm. It was found that all the micellar retinol formulations accelerated wound bed contraction, with 0.3% RMF demonstrating the highest efficacy. At the depths of 60 µm and 80 µm, the 0.3% RMF exhibited inner wound diameter contraction of 58% and 77%, respectively, in comparison to the placebo showing 15% and 8%. The RMF significantly accelerated wound healing and can thus be a potential early intervention for speedy wound recovery. It should be pointed out that these results were obtained based on a small sample size and a large sample size will be explored to further validate the results.

Microvascular Fragment-Loaded Platelet-Rich Plasma Dressing Promotes Cutaneous Wound Healing.

Objective: Chronic wounds represent a considerable burden for the affected patients and the health care system. To overcome this problem, effective treatment strategies are urgently required. In this study, we tested a novel approach by combining platelet-rich plasma (PRP) and microvascular fragments (MVF) to create a prevascularized gel dressing. Approach: MVF were enzymatically isolated from the epididymal fat pads of transgenic green fluorescent protein (GFP)+ C57BL/6J donor mice. Subsequently, 5,000 MVF were suspended in 10 μL murine PRP as carrier and transferred into full-thickness skin wounds within dorsal skinfold chambers of C57BL/6J wild-type mice (PRP+MVF). Wound healing in comparison to empty wounds (control) and wounds filled with PRP alone was repeatedly analyzed throughout 14 days by means of stereomicroscopy, histology, and immunohistochemistry. Results: Planimetric assessment of the wound size over time revealed a significantly accelerated and improved healing of PRP+MVF-treated wounds when compared with PRP-treated and empty control wounds. These wounds also exhibited a significantly higher density of blood and lymph vessels, which originated from the GFP+ MVF isolates and effectively promoted granulation tissue formation inside the skin defects. Innovation: This study is the first to combine PRP and MVF for the improvement of wound healing. Conclusion: The combination of PRP and MVF represents a promising approach for the future treatment of wounds that do not heal spontaneously due to poor wound-healing conditions.

Histological Assessment of the Effect Laser Irradiation on Full-Thickness Skin Wound Healing in Rabbits Models

Since there is currently no ideal treatment, wound healing impairment is a significant clinical challenge that is the subject of ongoing research into effective wound healing strategies. As a result, it has been demonstrated that low level laser therapy (LLLT), which is used for wound healing, can effectively control both the local and the systemic response. This study was conducted on 24 adult, clinically healthy male rabbits for this purpose. On each animal's back, full-thickness excisional wounds measuring 2 cm x 2 cm were created following sterile skin preparation. The animals were randomly split into two equal groups, each with twelve rabbits. In the group that acts as a control; 5 milliliters of phosphate-buffered saline was used to treat wounds. In the group treated; for the first seven days, the wounds were only treated with (LLLT) at a rate of 5/5 second at 8j/cm2. At the seventh, fourteenth, and 35th days of healing, histopathological biopsies were performed. The control group's histopathology revealed hemorrhage with inflammatory cell infiltration, primarily neutrophils, and congested blood vessels in the gap seven days after surgery. Necrotized neutrophils, hemolysis, and granulation tissue under the dermis were present in the gap at fourteen days. Between the muscle fibers, there was hemolysis. At 35 days, there was irregular proliferation of fibrous connective tissue, and congested blood vessels with mononuclear cell infiltration could be seen in the gap. At seven days, the treated group has completely sloughed the epidermis and a thin crust on the skin's surface with a small incision. In the dermis, there is a lot of infiltration of inflammatory cells, mostly lymphocytes and macrophages. There is also a lot of granulation tissue and a lot of adipose tissue with a lot of thick collagen network. At fourteen days, the epidermis' epithelial layers have healed completely and a keratinized layer is present. In the dermis, a proliferating and thick collagen network, scattered inflammatory cells, and regular fibrosis with hemorrhage and the development of a new B.V. At day 35, look for narrow scar tissue with complete epithelization, a keratinized layer above the epidermis, new vascularization with a lot of regular fibrosis and few regular collagen, new hair follicles, new blood vessels, and scattered macrophages. We concluded that full-thickness wound healing is positively influenced by the use of low level laser therapy (LLLT), which creates a microenvironment favorable to cell growth and differentiation.