Full-thickness Excisional Skin Research Articles

The Role of Mount Lawu Propolis in Modulating Oxidative Stress and Angiogenic Factors During the Proliferation Phase of Wound Healing

Background: The skin, the body's largest and first-line defense organ, is crucial for protection against environmental aggressors, thermoregulation, fluid balance, immune surveillance, sensory perception, and the intricate process of wound healing. This study investigated the modulatory role of Mount Lawu propolis extract on Malondialdehyde (MDA), a marker of oxidative stress, and Vascular Endothelial Growth Factor (VEGF), a key mediator of angiogenesis, during the critical proliferation phase of wound healing. Methods: A post-test-only control group design experimental study was conducted using twenty-four male rats (Rattus norvegicus). Following the creation of standardized full-thickness skin excision wounds, the rats were divided into four groups (n=6 per group): a control group receiving no propolis, and three treatment groups receiving topical applications of 200mg/kgBB (Group 1), 400mg/kgBB (Group 2), and 800mg/kgBB (Group 3) ethanol propolis extract daily for seven days. MDA and VEGF expression in granulated tissue samples were evaluated using immunohistochemistry and semi-quantitatively scored. Statistical analysis involved the Kruskal-Wallis non-parametric test, followed by the Mann-Whitney test due to non-normal data distribution. Results: MDA levels showed a significant reduction (p<0.05) in Group 2 (400mg/kgBB propolis) compared to the control, indicating a dose-specific antioxidant effect. VEGF expression demonstrated a significant increase (p<0.05) in all propolis-treated groups (Groups 1, 2, and 3) compared to the control, confirming the pro-angiogenic potential of propolis. Notably, the highest VEGF expression was observed in Group 3 (800mg/kgBB propolis). Conclusion: Mount Lawu ethanol propolis extract effectively modulated both oxidative stress and angiogenesis during the proliferation phase of wound healing in this rat model. A 400mg/kgBB/day dose of propolis optimally reduced MDA expression, while propolis at all doses, particularly 800mg/kgBB/day, significantly enhanced VEGF expression. These findings suggest propolis as a promising therapeutic agent to enhance wound healing by mitigating oxidative stress and promoting angiogenesis.

Zinc sulfate gel reshapes the wound microenvironment to promote full-thickness wound healing in mice.

Zinc sulfate gel reshapes the wound microenvironment to promote full-thickness wound healing in mice.

Regeneration of the skin wound by two different crosslinkers: In vitro and in vivo studies.

For designing a suitable hydrogel, two crosslinked Alginate/ Carboxymethyl cellulose (Alg/CMC) hydrogel, using calcium chloride (Ca2+) and glutaraldehyde (GA) as crosslinking agents were synthesized and compared. All samples were characterized by Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Blood compatibility (BC), Blood clotting index (BCI), weight loss (WL), water absorption (WA), pH, and Electrochemical Impedance Spectroscopy (EIS). Cell viability and cell migration were investigated using the MTT assay and the wound scratch test, respectively. Besides, the wound healing potential of prepared hydrogels was evaluated on the rat models with full-thickness skin excision. To further investigation, TGF β1, IGF-I, COL1, ACT-A (alfa-SMA), and GAPDH expression levels were also reported by RT-PCR. Water absorption and weight loss properties were compared between different crosslinker agents, and the most nontoxic crosslinker concentration was determined. We have shown that GA (20 µl/ml) and Ca2+ (50 or 75 mM) enhanced the physical stability of Alg-CMC hydrogel, and they are nontoxic and suitable crosslinkers for wound dressing applications. Although in vivo assessments indicated that the GA (20 µl/ml) had a cytotoxic effect on tissue repair, Ca2+ (75 mM) boosted the wound healing process. Further, RT-PCR results revealed that TGF β1, IGF-I, COL1, ACT-A (alfa-SMA), and GAPDH expression levels were increased in GA (20 µl/ml). Moreover, this trend is the opposite in the Ca2+ (75 mM) treatment groups. This research shows that Ca2+ (75 mM) boosts tissue regeneration and wound healing process.

Absorbable Meek skin graft material transplantation: A preliminary experimental study.

Absorbable Meek skin graft material transplantation: A preliminary experimental study.

Pd Icosahedral Nanoparticles Promote Skin Wound Healing by Enhancing SP1-HBEGF Axis-Mediated Keratinocytes Proliferation.

Impaired wound healing leads to compromised cutaneous barrier and dysfunction, which still remains a challenging problem. However, safe and efficient materials and treatments for promoting wound healing are still lacking. Metal nanoparticles especially palladium nanoparticles (Pd NPs) have attracted tremendous interests in medical application in recent years, due to its unique physicochemical properties and biological inertness. Thereinto, Pd icosahedra nanoparticles (Pd Icos NPs) and Pd octahedra nanoparticles (Pd Oct NPs) have superior catalytic activity compared to other shapes but the application in skin wound healing have not been studied and reported. Pd Oct NPs and Pd Icos NPs were synthesized by seed-mediated growth method and one-step synthesis method and characterized by series physical chemical assays. The acute full-thickness skin excision wound mouse model was used to access the wound healing potential and screen out the effective materials-Pd Icos NPs. Next evaluate the biotoxicity and safety of Pd Icos NPs and both in HaCaT cells and in vivo. Further examine related molecules expression by RT-qPCR and WB in HaCaT cells and wound tissues with Pd Icos treatment. Then knockout the related molecules both in HaCaT cells and in vivo to validate the molecular mechanism of these molecules in the phenotype of wound healing promoted by Pd Icos NPs. Pd Icos NPs with surface and tensile strain rather than Pd Oct NPs can promote skin wound healing. Pd Icos NPs upregulates the expression of HBEGF by promoting the production of transcription factor SP1, and contributes to keratinocytes proliferation and accelerating acute full-thickness skin wound healing. Pd Icos NPs represent an effective and safe material for skin wound healing, suggesting a potential novel therapeutic strategy.

Pickering Emulsion of Curcumin Stabilized by Cellulose Nanocrystals/Chitosan Oligosaccharide: Effect in Promoting Wound Healing.

Background: The stabilization of droplets in Pickering emulsions using solid particles has garnered significant attention through various methods. Cellulose and chitin derivatives in nature offer a sustainable source of Pickering emulsion stabilizers. Methods: In this study, medium-chain triglycerides were used as the oil phase for the preparation of emulsion. This study explores the potential of cellulose nanocrystals (CNC) and shell oligosaccharides (COS) as effective stabilizers for achieving stable Pickering emulsions. Optical microscopy, CLSM, and Cyro-SEM were employed to analyze CNC/COS-Cur, revealing the formation of bright and uniform yellow spherical emulsions. Results: CLSM and SEM results confirmed that CNC/COS formed a continuous and compact shell at the oil-water interface layer, enabling a stable 2~3 microns Pickering emulsion with CNS/COS-Cur as an oil-in-water emulsion stabilizer. Based on FTIR, XRD, and SEM analyses of CNC/COS, along with zeta potential measurements of the emulsion, we found that CNC and COS complexed via electrostatic adsorption, forming irregular rods measuring approximately 200-300 nm in length. An evaluation of the DPPH radical-scavenging ability demonstrated that the CNC/ COS-Cur Pickering emulsion performed well in vitro. In vivo experiments involving full-thickness skin excision surgery in rats revealed that CNC/COS-Cur facilitated wound repair processes. Measurements of the MDA and SOD content in healing tissues indicated that the CNC/COS-Cur Pickering emulsion increased SOD levels and reduced MDA content, effectively countering oxidative stress-induced damage. An assessment based on wound-healing rates and histopathological examination showed that CNC/COS-Cur promoted granulation tissue formation, fibroblast proliferation, angiogenesis, and an accelerated re-epithelialization process within the wound tissue, leading to enhanced collagen deposition and facilitating rapid wound-healing capabilities. An antibacterial efficacy assessment conducted in vitro demonstrated antibacterial activity.

Spiny mice are primed but fail to regenerate volumetric skeletal muscle loss injuries

BackgroundIn recent years, the African spiny mouse Acomys cahirinus has been shown to regenerate a remarkable array of severe internal and external injuries in the absence of a fibrotic response, including the ability to regenerate full-thickness skin excisions, ear punches, severe kidney injuries, and complete transection of the spinal cord. While skeletal muscle is highly regenerative in adult mammals, Acomys displays superior muscle regeneration properties compared with standard laboratory mice following several injuries, including serial cardiotoxin injections of skeletal muscle and volumetric muscle loss (VML) of the panniculus carnosus muscle following full-thickness excision injuries. VML is an extreme muscle injury defined as the irrecoverable ablation of muscle mass, most commonly resulting from combat injuries or surgical debridement. Barriers to the treatment of VML injury include early and prolonged inflammatory responses that promote fibrotic repair and the loss of structural and mechanical cues that promote muscle regeneration. While the regeneration of the panniculus carnosus in Acomys is impressive, its direct relevance to the study of VML in patients is less clear as this muscle has largely been lost in humans, and, while striated, is not a true skeletal muscle. We therefore sought to test the ability of Acomys to regenerate a skeletal muscle more commonly used in VML injury models.MethodsWe performed two different VML injuries of the Acomys tibialis anterior muscle and compared the regenerative response to a standard laboratory mouse strain, Mus C57BL6/J.ResultsNeither Acomys nor Mus recovered lost muscle mass or myofiber number within three months following VML injury, and Acomys also failed to recover force production better than Mus. In contrast, Acomys continued to express eMHC within the injured area even three months following injury, whereas Mus ceased expressing eMHC less than one-month post-injury, suggesting that Acomys muscle was primed, but failed, to regenerate.ConclusionsWhile the panniculus carnosus muscle in Acomys regenerates following VML injury in the context of full-thickness skin excision, this regenerative ability does not translate to regenerative repair of a skeletal muscle.

An injectable hydrogel of porcine cholecyst extracellular matrix for accelerated wound healing.

Hydrogel formulations of xenogeneic extracellular matrices have been widely used for topical wound care because of their exceptional tunability over other formulations like lyophilized sheets, powders, non-injectable gels, pastes, and ointments. This is important in the treatment of wounds with irregular shapes and depth. This study identified an injectable hydrogel formulation of porcine cholecyst extracellular matrix (60%) in medical-grade carboxymethyl cellulose (40%) as vehicle and evaluated its biomaterial properties. Further, an in-depth evaluation of in vivo wound healing efficacy was conducted in a rat full-thickness skin excision wound healing model, which revealed that the hydrogel formulation accelerated wound healing process compared to wounds treated with a commercial formulation and untreated wounds. The hydrogel appeared to have promoted a desirable pro-regenerative tissue reaction predominated by Th2 helper lymphocytes and M2 macrophages as well as an effective collagen remodeling indicative of diminished scarring. In conclusion, the porcine cholecyst extracellular matrix injectable hydrogel formulation appeared to be a promising candidate formulation as an advanced wound care biomaterial for faster healing of skin wounds with minimal scarring.

Pyroxylin-based liquid bandage forms a mechanically active protective film to facilitate skin wound healing in mice

Pyroxylin-based liquid bandage forms a mechanically active protective film to facilitate skin wound healing in mice

Accelerated full-thickness skin wound tissue regeneration by self-crosslinked chitosan hydrogel films reinforced by oxidized CNC-AgNPs stabilized Pickering emulsion for quercetin delivery

BackgroundThe non-toxic self-crosslinked hydrogel films designed from biocompatible materials allow for controlled drug release and have gathered remarkable attention from healthcare professionals as wound dressing materials. Thus, in the current study the chitosan (CS) film is infused with oil-in-water Pickering emulsion (PE) loaded with bioactive compound quercetin (Qu) and stabilized by dialdehyde cellulose nanocrystal-silver nanoparticles (DCNC-AgNPs). The DCNC-AgNPs play a dual role in stabilizing PE and are involved in the self-crosslinking with CS films. Also, this film could combine the advantage of the controlled release and synergistic wound-healing effect of Qu and AgNPs.ResultsThe DCNC-AgNPs were synthesized using sodium periodate oxidation of CNC. The DCNC-AgNPs were used to stabilize oil-in-water PE loaded with Qu in its oil phase by high speed homogenization. Stable PEs were prepared by 20% v/v oil: water ratio with maximum encapsulation of Qu in the oil phase. The Qu-loaded PE was then added to CS solution (50% v/v) to prepare self-crosslinked films (CS-PE-Qu). After grafting CS films with PE, the surface and cross-sectional SEM images show an inter-penetrated network within the matrix between DCNC and CS due to the formation of a Schiff base bond between the reactive aldehyde groups of DCNC-AgNPs and amino groups of CS. Further, the addition of glycerol influenced the extensibility, swelling ratio, and drug release of the films. The fabricated CS-PE-Qu films were analyzed for their wound healing and tissue regeneration potential using cell scratch assay and full-thickness excisional skin wound model in mice. The as-fabricated CS-PE-Qu films showed great biocompatibility, increased HaCat cell migration, and promoted collagen synthesis in HDFa cells. In addition, the CS-PE-Qu films exhibited non-hemolysis and improved wound closure rate in mice compared to CS, CS-Qu, and CS-blank PE. The H&E staining of the wounded skin tissue indicated the wounded tissue regeneration in CS-PE-Qu films treated mice.ConclusionResults obtained here confirm the wound healing benefits of CS-PE-Qu films and project them as promising biocompatible material and well suited for full-thickness wound healing in clinical applications.Graphical

Modulating the hAM/PCL Biocomposite for Expedited Wound Healing: A Chemical-Free Approach for Boosting Regenerative Potential.

There is an arising need for effective wound dressings that retain the bioactivity of a cellular treatment, but without the high costs and complexities associated with manufacturing, storing, and applying cell-based products. As skin wound recovery is a dynamic and complicated process, a significant obstacle to the healing of skin wounds is the lack of an appropriate wound dressing that can imitate the microenvironment of healthy skin and prevent bacterial infection. It requires the well-orchestrated integration of biological and molecular events. In this study, we have fabricated full-thickness skin graft biocomposite membranes to target full-thickness skin excision wounds. We reinforced human amniotic membrane (hAM) with electrospun polycaprolactone (PCL) to develop composite membranes, namely, PCL/hAM and PCL/hAM/PCL. Composite membranes were compared for physical, biological, and mechanical properties with the native counterpart. PCL/hAM and PCL/hAM/PCL displayed improved stability and delayed degradation, which further synergically improved the rapid wound healing property of hAM, driven primarily by wound closure analysis and histological assessment. Moreover, PCL/hAM displayed a comparable cellular interaction to hAM. On application as a wound dressing, histological analysis demonstrated that hAM and PCL/hAM promoted early epidermis and dermis formation. Studies on in vivo wound healing revealed that although hAM accelerates cell development, the overall wound healing process is similar in PCL/hAM. This finding is further supported by the immunohistochemical analysis of COL-1/COL-3, CD-31, and TGF-β. Overall, this conjugated PCL and hAM-based membrane has considerable potential to be applied in skin wound healing. The facile fabrication of the PCL/hAM composite membrane provided the self-regenerating wound dressing with the desired mechanical strength as an ideal regenerative property for skin tissue regeneration.

Nanosheet Promotes Chronic Wound Healing by Localizing Uncultured Stromal Vascular Fraction Cells.

Objective: To develop an efficacious and efficient method for treating chronic wounds using "nanosheet" that improves the survival and localization of transplanted cells without prior seeding to optimally derive the regenerative potentials of uncultured stromal vascular fraction (SVF) cells. Approach: We propose a method whereby the wound is covered by uncultured SVF cells using the nanosheet [porous poly(d, l,-lactic acid)] (PDLLA) films) designed to hold cells in a single-cell layer. A chronic wound model was created on 12-month-old db/db mice by inflecting a full-thickness skin excision on their dorsum and was subsequently given either no treatment or a treatment with SVF cells alone (with Tegaderm dressing), nanosheet alone, or nanosheet with SVF cells. Results: The placement of the nanosheet improved the grafted cell retention rate at day 10 timepoint by 5 folds, and the wound area was the smallest in the wounds treated with SVF cells plus nanosheet in comparison to the other groups. Collagen deposition and epidermal growth factor were significantly higher in the wound beds treated with SVF cells with the nanosheet, offering some mechanistic insights. Innovation: Porous poly(d, l,-lactic acid acid) (PDLLA) films or "nanosheet" printed on the nanoscale (1-100 nm in thickness) as a cellular scaffold for cytotherapy for the treatment of chronic wounds. Conclusion: The use of the nanosheet is an effective way to improve the transplanted SVF cell retention and accelerate the overall wound closure.

Dendrobium officinale Kinura et Migo glycoprotein promotes skin wound healing by regulating extracellular matrix secretion and fibroblast proliferation on the proliferation phase.

Dendrobium officinale Kinura et Migo (DOKM) has a variety of medicinal applications; however, its ability to promote wound healing has not been previously reported. The purpose of this study is to investigate the proliferative phase of the wound-healing effect of DOKM glycoprotein (DOKMG) in rats and to elucidate its mechanism of action in vitro. In the present study, the ointment mixture containing DOKMG was applied to the dorsal skin wounds of the full-thickness skin excision rat model, and the results showed that the wound healing speed was faster in the proliferative phase than vaseline. Histological analysis demonstrates that DOKMG promoted the re-epithelialization of wound skin. Immunofluorescence staining and quantitative polymerase chain reaction assays revealed that DOKMG promotes the secretion of Fibronectin and inhibits the secretion of Collagen IV during the granulation tissue formation period, indicating that DOKMG could accelerate the formation of granulation tissue by precisely regulating extracellular matrix (ECM) secretion. In addition, we demonstrated that DOKMG enhanced the migration and proliferation of fibroblast (3T6 cell) in two-dimensional trauma by regulating the secretion of ECM, via a mechanism that may implicate the AKT and JAK/STAT pathways under the control of epidermal growth factor receptor (EGFR) signalling. In summary, we have demonstrated that DOKMG promotes wound healing during the proliferative phase. Therefore, we suggest that DOKMG may have a potential therapeutic application for the treatment and management of cutaneous wounds.

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 < 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.

Promotion of skin wound healing using hypoimmunogenic epidermal cell sheets

Promotion of skin wound healing using hypoimmunogenic epidermal cell sheets

Dasatinib Ointment Promotes Healing of Murine Excisional Skin Wound.

Dasatinib, a tyrosine kinase inhibitor, has been shown to produce anti-inflammatory activity and impair vascular integrity in vivo, including during skin wound healing, potentially promoting the repair process. Given that dasatinib is a lipophilic small molecule capable of penetrating skin, topical dasatinib might provide benefits in wound healing. In the present study, we investigated the impact of dasatinib ointments in skin wound healing in mice. A full thickness excisional skin wound (4 mm diameter) was generated on the shaved dorsum of eight-week-old C57BL/6 mice. Dasatinib ointment (0.1 or 0.2% w/w) or ointment base was applied twice daily (every 12 h) for 10 days. Elizabethan collars were used to prevent animal licking. The wound size was monitored daily for 14 days. The results showed that dasatinib ointments, particularly 0.1% dasatinib, promoted a 16-23% reduction in wound size (p < 0.05) during day 2 to day 6 postinjury compared to controls. Immunohistochemistry analyses demonstrated a reduction in wound neutrophils (38% reduction, p = 0.04), macrophages (47% reduction, p = 0.005), and tumor necrosis factor-α levels (73% reduction, p < 0.01), together with an induction of vascular leakage-mediated fibrin(ogen) accumulation (2.5-fold increase, p < 0.01) in the wound during day 3 postinjury (an early phase of repair) in 0.1% dasatinib-treated mice relative to control mice. The anti-inflammatory and vascular hyperpermeability activities of dasatinib were associated with an enhanced healing process, including increased keratinocyte proliferation (1.8-fold increase in Ki67+ cells, p < 0.05) and augmented angiogenesis (1.7-fold increase in CD31+ area, p < 0.05), compared to the ointment base-treated group. Following treatment with 0.2% dasatinib ointment, minor wound bleeding and scab reformation were observed during the late phase, which contributed to delayed healing. In conclusion, our data suggest that dasatinib ointment, mainly at 0.1%, promotes the repair process by reducing inflammation and producing a local and temporal vascular leakage, leading to an increase in fibrin(ogen) deposition, re-epithelialization, and angiogenesis. Therefore, topical dasatinib might be a potential novel candidate to facilitate skin wound healing.

153. Quantification of Lymphangiogenesis in Murine Lymphedema Tail Model Using Intravital Microscopy

PURPOSE: Lymphedema is limb swelling caused by lymphatic dysfunction. It occurs in 30% of patients that undergo axillary lymph node dissection in the treatment of breast cancer. There is no cure for this disease. Understanding the mechanisms of lymphatic growth will play a pivotal role in developing therapeutic strategies against these conditions. Visualization of lymphangiogenesis and functional assessment remains a challenge. Intravital two-photon microscopy (IVM) is a powerful imaging tool for investigating various biological processes in live animals. Tissue nanotransfection technology (TNT) facilitates a direct, transcutaneous non-viral vector gene delivery using a chip with nanochannel poration in a rapid (<100ms) focused electric field. TNT was used in this study to deliver the genetic cargo in the murine tail lymphedema to assess the lymphangiogenesis. The purpose of this study is to experimentally evaluate the applicability of IVM to visualize and quantify lymphatics. METHODS: The murine tail model of lymphedema was utilized. A 3 mm full thickness skin excision and lymphatic vessel disruption was performed 20 mm from the base of the tail in twelve C57BL/6 mice. TNT was applied to the murine tail (day 0) directly at the surgical site with genetic cargo loaded into the TNT reservoir: Group I (control) was given pCMV6 (expression vector backbone alone) (n=6); Group II had pCMV6-Prox1 (n=6). Post-TNT (day 10), a 3 cm segment of murine tail was deskinned distal to the site of occlusion to optimize visualization. FITC-Dextran (2000 kD) injected intradermally at the distal tail region for lymphatic uptake. Lymphatic vessels are visualized at the second skin excision site with the Leica SP8 Confocal/Multiphoton Microscope and assessed for number of branching points to determine the newly formed lymphatics. Lymphatic vessel density was also observed by immunostaining with anti-Podoplanin antibody. RESULTS:The experimental group II exhibited increased branching points (3-fold) using filamentation analysis compared to control group I at the site of TNT treatment (n=6, p<0.05). Increased lymphatic vessel density was also observed with Podoplanin immunostaining post-TNT application. Intensity quantification of immunohistochemistry revealed greater expression of Podoplanin in Group II when compared to Group I (n=6, p<0.05). CONCLUSION:This study demonstrates a novel, powerful imaging tool for investigating lymphatic vessels in live murine tail model of lymphedema. Intravital microscopy can be utilized for functional assessment of lymphatics and visualization of lymphangiogenesis following gene-based therapy.

Pilose antler extract restores type I and III collagen to accelerate wound healing

Pilose antler extract restores type I and III collagen to accelerate wound healing

Fabrication of Fibrin/Polyvinyl Alcohol Scaffolds for Skin Tissue Engineering via Emulsion Templating

In the search for a novel and scalable skin scaffold for wound healing and tissue regeneration, we fabricated a class of fibrin/polyvinyl alcohol (PVA) scaffolds using an emulsion templating method. The fibrin/PVA scaffolds were formed by enzymatic coagulation of fibrinogen with thrombin in the presence of PVA as a bulking agent and an emulsion phase as the porogen, with glutaraldehyde as the cross-linking agent. After freeze drying, the scaffolds were characterized and evaluated for biocompatibility and efficacy of dermal reconstruction. SEM analysis showed that the formed scaffolds had interconnected porous structures (average pore size e was around 330 µm) and preserved the nano-scale fibrous architecture of the fibrin. Mechanical testing showed that the scaffolds' ultimate tensile strength was around 0.12 MPa with an elongation of around 50%. The proteolytic degradation of scaffolds could be controlled over a wide range by varying the type or degree of cross-linking and by fibrin/PVA composition. Assessment of cytocompatibility by human mesenchymal stem cell (MSC) proliferation assays shows that MSC can attach, penetrate, and proliferate into the fibrin/PVA scaffolds with an elongated and stretched morphology. The efficacy of scaffolds for tissue reconstruction was evaluated in a murine full-thickness skin excision defect model. The scaffolds were integrated and resorbed without inflammatory infiltration and, compared to control wounds, promoted deeper neodermal formation, greater collagen fiber deposition, facilitated angiogenesis, and significantly accelerated wound healing and epithelial closure. The experimental data showed that the fabricated fibrin/PVA scaffolds are promising for skin repair and skin tissue engineering.

A Protocol for Constructing a Rat Wound Model of Type 1 Diabetes

A single high dose of streptozotocin injection followed by full-thickness skin excision on the dorsum of rats is a common method for constructing animal models of type 1 diabetic wounds. However, improper manipulation can lead to model instability and high mortality in rats. Unfortunately, there are few existing guidelines on type 1 diabetic wound modeling, and they lack detail and do not present specific reference strategies. Therefore, this protocol details the complete procedure for constructing a type 1 diabetic wound model and analyzes the progression and angiogenic characteristics of the diabetic wounds. Type 1 diabetic wound modeling involves the following steps: preparation of the streptozotocin injection, induction of type 1 diabetes mellitus, and construction of the wound model. The wound area was measured on day 7 and day 14 after wounding, and the skin tissues of the rats were extracted for histopathological and immunofluorescence analysis. The results revealed that type 1 diabetes mellitus induced by 55 mg/kg streptozotocin was associated with lower mortality and a high success rate. The blood glucose levels were relatively stable after 5 weeks of induction. The diabetic wound healing rate was significantly lower than that of normal wounds on day 7 and day 14 (p < 0.05), but both could reach more than 90% on day 14. Compared with the normal group, the epidermal layer closure of diabetic wounds on day 14 was incomplete and had delayed re-epithelialization and significantly lower angiogenesis (p < 0.01). The type 1 diabetic wound model constructed based on this protocol has the characteristics of chronic wound healing, including poor closure, delayed re-epithelialization, and decreased angiogenesis compared to normal rat wounds.