Full-thickness Wound Model Research Articles

In Situ-Forming, Adhesive, and Antioxidant Chitosan Hydrogels for Accelerated Wound Healing.

Antioxidant hydrogels that can provide a moist environment and scavenge reactive oxygen species have emerged as highly potential wound dressing materials. In situ-forming and good tissue adhesiveness will make them more desirable, as they can fill the irregular wound defect, stick to the wound, and offer intimate contact with the wound. Herein, a hydrogel dressing combining in situ-forming, good tissue adhesiveness, and excellent antioxidant capabilities was developed by simply conjugating dopamine onto carboxymethyl chitosan. The introduction of dopamine allows in situ gelation of the polymer under mild conditions using an HRP-catalyzed cross-linking reaction. The introduction of dopamine also endows the hydrogels with suitable tissue-adhesion properties. Excellent antioxidant properties were also imparted as a result of the introduction of dopamine. Thanks to the favorable moist environment provided by the hydrogel and the effectively mitigated oxidative stress at wound sites, accelerated healing and reduced scar formation were observed in a rat full-thickness skin wound model.

Phytochemical investigation, role in wound healing process and cytotoxicity of Sphagneticola trilobata: In vitro, in vivo and in silico approach.

Sphagneticola trilobata was traditionally used to alleviate wounds using topical plant preparations. The precise mechanism of the plant responsible for its wound healing effect are still unclear. Although the plant was reported to be cytotoxic, there is a lack of reported data regarding its cytotoxic impact on skin cancer. To in-depth investigate wound healing and cytotoxic effects of the plant extracts and its fractions by using different assays. In vitro scratch assay and in vivo full-thickness wound model were performed to evaluate the plant's wound healing activity. Enzyme-linked immunosorbent assay kits were employed to assess key skin parameters levels. The cytotoxicity was evaluated using in vitro Western Standard Time assay against skin carcinoma cells. Sphagneticola trilobata improved the wound closure percentage in both in vitro scratch assay and in vivo model by modulating inflammation, as evidenced by a reduction in tumor necrosis factor and mitogen activated protein kinase levels, and enhancing proliferation via elevating collagen, smooth muscle actin, and forkhead protein. The total extract's efficacy surpassed the effectiveness of reference ointment. The non-polar fraction outperformed the polar one in accelerating wound closure and improving the tested skin parameters levels. Trilobolide-6-O-isobutyrate displayed the best docking scores for the selected target receptors. Moreover, the non-polar fraction demonstrated the most powerful cytotoxic effect against skin cancer cells. A specific compound mixture (kaurenoic acid/grandiflorenic acid, 1 and 2) within this fraction exhibited stronger cytotoxicity. Sphagneticola trilobata can be considered as a promising therapeutic agent in relieving wounds and combating skin cancer cell lines.

Photosynthesis-Inspired NIR-Triggered Fe₃O₄@MoS₂ Core-Shell Nanozyme for Promoting MRSA-Infected Diabetic Wound Healing.

Bacterial infections can lead to severe medical complications, including major medical incidents and even death, posing a significant challenge in clinical trauma repair. Consequently, the development of new, efficient, and non-resistant antimicrobial agents has become a priority for medical practitioners. In this study, a stepwise hydrothermal reaction strategy is utilized to prepare Fe3O4@MoS2 core-shell nanoparticles (NPs) with photosynthesis-like activity for the treatment of bacterial infections. The Fe3O4@MoS2 NPs continuously catalyze the production of reactive oxygen species (ROS) from hydrogen peroxide through photosynthesis-like reactions and convert light energy into heat with a photothermal efficiency of 30.30%. In addition, the photosynthetically generated ROS, combined with the iron-induced cell death mechanism of the Fe3O4@MoS2 NPs, confer them with exceptional and broad-spectrum antibacterial properties, achieving antimicrobial activities of up to 98.62% for Staphylococcus aureus, 99.22% for Escherichia coli, and 98.55% for methicillin-resistant Staphylococcus aureus. The composite exhibits good cell safety and hemocompatibility. Finally, a full-thickness diabetic wound model validates the significant pro-healing properties of Fe3O4@MoS2 in chronic diabetic wounds. Overall, the design of photosynthesis-inspired Fe3O4@MoS2 presents new perspectives for developing efficient photothermal nano-enzymatic compounds, offering a promising solution to the challenges of antimicrobial drug resistance and antibiotic misuse.

Composite Hyaluronic Acid Gas-Entrapping Materials to Promote Wound Healing.

Tissue repair is often impaired in pathological states, highlighting the need for innovative wound-healing technologies. This study introduces composite hyaluronic acid gas-entrapping materials (GEMs) delivering carbon monoxide (CO) to promote wound healing in pigs. These composite materials facilitate burst release followed by sustained release of CO over 48 h. In a porcine full-thickness wound model, CO-GEMs significantly accelerated wound closure compared to the standard-of-care dressing (Tegaderm). Wound area closure with CO-GEMs was 68.6% vs 56.8% on day 14, 41.0% vs 25.1% on day 28, and 26.9% vs 11.8% on day 42, effectively reducing healing time by 14 days. Histological analysis revealed increased epithelialization and neovascularization with reduced inflammation. These findings demonstrate the potential of CO-GEMs as a topical therapeutic to enhance tissue repair in clinically relevant models, supporting further testing for wound-healing applications.

Hydrogen-Rich Saline Combined With Vacuum Sealing Drainage Promotes Wound Healing by Altering Biotin Metabolism.

Impaired wound healing affects the life quality of patients and causes a substantial financial burden. Hydrogen-rich medium is reported to have antioxidant and anti-inflammatory effects. However, the role of hydrogen-rich saline (HRS) in cutaneous wound healing remains largely unexplored, especially by metabolomics. Thus, untargeted metabolomics profiling was analysed to study the effects and mechanism of HRS combined with vacuum sealing drainage (VSD) in a rabbit full-thickness wound model. Our results indicated that the combination treatment of HRS and VSD could accelerate wound healing. Invitro experiments further confirmed its effects on HaCaT keratinocytes. We found that 45 metabolites were significantly changed between the VSD + HRS group and the VSD + saline-treated group. Pathway enrichment analysis indicated that biotin metabolism was the potential target pathway. The biochemical interpretation analysis demonstrated that combining HRS and VSD might enhance mitochondrial function, ATP synthesis, and GSH homeostasis by altering biotin metabolism. The detection of representative indicators of oxidative stress supported the critical metabolic pathway analysis as well. In summary, VSD combined with HRS might provide a new strategy to enhance wound healing.

3D-Printed Hydrogel Scaffolds Loaded with Flavanone@ZIF-8 Nanoparticles for Promoting Bacteria-Infected Wound Healing.

Bacterial-infected skin wounds caused by trauma remain a significant challenge in modern medicine. Clinically, there is a growing demand for wound dressings with exceptional antibacterial activity and robust regenerative properties. To address the need, this study proposes a novel multifunctional dressing designed to combine efficient gas exchange, effective microbial barriers, and precise drug delivery capabilities, thereby promoting cell proliferation and accelerating wound healing. This work reports the development of a 3D-printed hydrogel scaffold incorporating flavanone (FLA)-loaded ZIF-8 nanoparticles (FLA@ZIF-8 NPs) within a composite matrix of κ-carrageenan (KC) and konjac glucomannan (KGM). The scaffold forms a stable dual-network structure through the chelation of KC with potassium ions and intermolecular hydrogen bonding between KC and KGM. This dual-network structure not only enhances the mechanical stability of the scaffold but also improves its adaptability to complex wound environments. In mildly acidic wound conditions, FLA@ZIF-8 NPs release Zn2+ and flavanone in a controlled manner, providing sustained antibacterial effects and promoting wound healing. In vivo studies using a rat full-thickness infected wound model demonstrated that the FLA@ZIF-8/KC@KGM hydrogel scaffold significantly accelerated wound healing, showcasing its superior performance in the treatment of infected wounds.

Electrospun 11β-HSD1 Inhibitor-Loaded Scaffolds for Accelerating Diabetic Ulcer Healing.

Diabetic ulcers (DUs) are a common and severe complication of diabetes, characterized by impaired wound healing due to a complex pathophysiological mechanism. Elevated levels of 11β-hydroxysteroid dehydrogenase type I (11β-HSD1) in wounds have been demonstrated to modulate glucocorticoid activity, leading to delayed skin cell proliferation and restricted angiogenesis, ultimately hindering wound healing. In this study, we propose an electrospun poly(ε-caprolactone) (PCL) nanofiber scaffold doped with the 11β-HSD1 inhibitor BVT2733 (BPs) to prevent 11β-HSD1 activity during the diabetic wound healing process. The electrospun scaffold loaded with BVT2733 is designed to achieve localized inhibition of 11β-HSD1 in DUs. This scaffold exhibited a porous morphology and desirable drug-loading capacity, meeting the requirements for wound coverage and effective delivery of BVT2733 BPs. In vitro studies demonstrated that the sustained release of BVT2733 from the scaffold promoted skin cell proliferation and migration while stimulating angiogenesis by upregulating HIF1-α/VEGF expression. The therapeutic effect of the scaffold was further confirmed in a full-thickness wound model using diabetic mice. The mice treated with the scaffolds exhibited an accelerated wound healing rate, increased neovascularization, enhanced collagen deposition, and regeneration of skin appendages within 2 weeks postinjury. The findings here provide evidence for the use of 11β-HSD1 inhibitor-integrated biomaterials in treating DUs and represent a novel biological platform for modulating dysregulated mechanisms in DUs.

Curcumin-release antibacterial dressings with antioxidation and anti-inflammatory function for diabetic wound healing and glucose monitoring.

Diabetic wound healing remains a challenge due to high levels of oxidative stress, excessive inflammation, and bacterial infection. Smart dressings loaded with natural active monomers are proving to be effective strategies for enhancing diabetic wound healing. Herein, the bio-composites (PTIGA-Cur and PTIGA-Cur-Ag) with curcumin (Cur) responsive release were reported for promoting angiogenesis and diabetic wound repair, showing excellent anti-inflammatory, antioxidant, and antibacterial properties. The integration of three-dimensional networks and chemical bonds endowed the bio-composites with superior thermodynamic, mechanical, and self-healing properties. Notably, pH-responsive Schiff base as well as ester groups in the matrix enable the Cur to be released in a controlled manner. A biosensor assembled from PTIGA-Cur-Ag demonstrated electronic conductivity based on in-situ synthesis of AgNPs, which enabled sensitive monitoring of blood glucose levels. In addition, the release of AgNPs enhanced the antibacterial and anti-inflammatory properties. Expectedly, the bio-composites exhibited remarkable biocompatibility, effectively promoting the polarization of macrophages to M2 phenotype, and reducing the expression of proinflammatory cytokines. The full-thickness diabetic wound model revealed that PTIGA-Cur and PTIGA-Cur-Ag were able to effectively promote collagen deposition, neovascularization, and granulation tissue regeneration through their anti-inflammatory, antioxidant, and antibacterial properties. This study provides evidence supporting the potential utility of bio-composites with both pro-healing properties and monitoring functions in the management of diabetic wounds.

Botulinum toxin type A inhibits the formation of hypertrophic scar through the JAK2/STAT3 pathway.

Hypertrophic scar (HS) is a fibrous proliferative disorder that occurs in the dermis after skin injury. Studies have confirmed that Botulinum toxin type A (BTA) is effective in scar prevention and treatment. However, the specific mechanism remains uncertain. Hypertrophic scar fibroblasts (HSFs) and normal skin fibroblasts (NSFs) from the skin tissues of HS patients were isolated and cultured. Western blot analysis was conducted to measure the expression of JAK2/STAT3 pathway-related proteins. HSFs were treated with the JAK2 inhibitor (AG490) or agonist (C-A1). The CCK-8 assay, EdU staining, scratch-wound assay and transwell assay were used to examine the biological properties of HSFs. Western blot, immunofluorescence, and Sirius red staining were used to assess the fibrosis of HSFs. Additionally, a mouse full-thickness wound model was constructed to investigate the role of BTA in wound healing. The results showed that the JAK2 and STAT3 phosphorylation levels were markedly increased in HS tissues and HSFs. AG490 treatment reduced cell viability, proliferation and migration capacity, and inhibited the fibrosis of HSFs, whereas C-A1 treatment had the opposite effect. BTA treatment inhibited the JAK2/STAT3 pathway. BTA reduced cell viability, proliferation and migration ability, and inhibited the fibrosis of HSFs, while C-A1 intervention weakened the impact of BTA. Meanwhile, BTA promoted wound healing and reduced collagen deposition in vivo. In conclusion, BTA inhibited the JAK2/STAT3 pathway, which in turn hindered the proliferation, migration and fibrosis of HSFs, and promoted wound healing in mice.

Injectable self-healing alginate/PEG hydrogels cross-linked via thiol-Michael addition bonds for hemostasis and wound healing

In this study, an alginate/PEG hydrogel was developed via a thiol-Michael addition reaction between oxidized quinone of catechols on dopamine-grafted sodium alginate (SA-DA) and sulfhydryl groups of 4-arm polyethylene glycol tetra-thiol (4-arm PEG-SH) under mildly basic conditions. Through the formation of thiol-terminated catechol groups, the accompanying oxidized catechols are reduced, significantly strengthening the internal network structure of the hydrogel and improving tissue adhesion. Meanwhile, the hydrogels have excellent self-healing properties due to the dynamic non-covalent bonds between the groups. Adjustment of hydrogel properties by varying the mass ratio of two hydrogel precursors. Due to the high content of thiol-terminated catechol groups, the Gel 3 exhibited good tissue adhesion, rapid self-healing ability, and other multifunctions beneficial to wound healing, including killing of E. coli and S. aureus, rapid hemostasis and promoting migration of L929 cells. The full-thickness skin wound model shows that the hydrogel dressing significantly accelerated wound contraction, with increased granulation tissue thickness, collagen disposition, and enhanced vascularization, thus promoting wound healing. Therefore, the thiol-Michael addition reaction is an effective method for creating multifunctional hydrogels, and the injectable self-healing alginate/PEG hydrogels prepared in this way could be used in the biomedical area as wound healing dressing materials.

Evaluation of a Kenaf Nanocrystalline Cellulose-based Hydrogel Containing Platelet Lysate for Full-thickness Wound Healing

Introduction: Healing full-thickness wounds is often challenging and time-consuming, with complications such as scarring and infections. The standard treatment, split skin grafting, has limitations due to the availability of healthy donors and suitability for immunocompromised patients. Method: Autologous platelet lysate (PL) has been popular for tissue regenerative potential because it contains growth factors (GF) and is a safer option for bedridden patients with weak immune systems. However, PL has inconsistent clinical efficacy, high costs, and a short half-life. To address these issues, this study explores a novel delivery system by fabricating a chitosan/nanocrystalline cellulose (CS/NCC) hydrogel to sustainably deliver autologous PL to the wound site. Notably, NCC was prepared from kenaf bast fibers using acid hydrolysis and integrated into the CS matrix through physical entrapment without any chemical crosslinkers. The composite hydrogel was then enriched with autologous PL and further characterized for its physicochemical properties, in vitro GF release, and compatibility with skin cells. At the molecular level, gene expression of wound healing genes was facilitated using qPCR, revealing that the PL-supplemented hydrogel upregulated the expression of extracellular matrix genes. An in vivo study using a full-thickness wound model demonstrated that the CS-NCC-PL hydrogel dressing achieved 81.8% wound closure within 14 days, compared to the control groups. Result: Histological analysis indicated enhanced re-epithelialization, angiogenesis, and collagen deposition. Particularly, the CS-NCC-PL hydrogel group showed a significantly higher hydroxyproline content (60.62 ± 11.46 μg/100 mg) by day 14. Immunohistochemistry results revealed elevated levels of α-SMA and CD31, markers of myofibroblast presence and angiogenesis, peaking at day 7. Conclusion: These findings suggest that the CS-NCC-PL hydrogel is a promising personalized wound dressing for bedridden patients, offering improved healing outcomes in hospital settings.

Inhibition of Ubiquitin C-Terminal Hydrolase L1 Facilitates Cutaneous Wound Healing via Activating TGF-β/Smad Signalling Pathway in Fibroblasts.

Ubiquitin C-terminal hydrolase L1 (UCHL1) plays vital roles in cell proliferation, angiogenesis, inflammation and oxidative stress. Nevertheless, it is unclear whether UCHL1 could regulate the biologic behaviour of cells and ultimately influences wound healing. We aim to illustrate the roles and the underlying mechanism of UCHL1 in cutaneous wound healing. Murine full-thickness excisional wound model was utilised to study the effects of UCHL1 on wound healing through topical administration of the UCHL1 inhibitor LDN57444, followed by assessment of wound areas and histological alterations. Subsequently, ethynyldeoxyuridine, scratch and transwell assays were performed to examine fibroblast migration and proliferation. The extracellular matrix (ECM)-related genes expression and transforming growth factor-β (TGF-β)/Smad signalling pathways activation were investigated by immuno-fluorescent staining, Western blots and quantitative reverse transcription polymerase chain reaction. We identified elevated UCHL1 expression in non-healing wound tissues. The UCHL1 expression displayed a dynamic change and reached a peak on Day-7 post-wounding during the healing process in mice. Cutaneous administration of LDN57444 promoted wound healing by facilitating collagen deposition, myofibroblast activation and angiogenesis. Invitro experiments demonstrated that UCHL1 concentration dependently inhibited migration, ECM synthesis and activation of human dermal fibroblasts, which was mechanistically related to downregulation of TGF-β/Smad signalling. Furthermore, these effects could be reversed by TGF-β inhibitor SB431542. Our findings reveal that UCHL1 is a negative regulator of cutaneous wound healing and considered as a novel prospective therapeutic target for effective wound healing.

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.

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.

Self-assembled ROS-triggered Bletilla striata polysaccharide-releasing hydrogel dressing for inflammation-regulation and enhanced tissue-healing

The antimicrobial and pro-healing properties remain critical clinical objectives for skin wound management. However, the escalating problem of antibiotic overuse and the corresponding rise in bacterial resistance necessitates an urgent shift towards an antibiotic-free approach to antibacterial treatment. The quest for antimicrobial efficacy while accelerating wound healing without antibiotic treatment have emerged as innovative strategies in skin wound treatment. Here, a dual-function hydrogel with antimicrobial and enhanced tissue-healing properties was developed by utilizing cyclodextrin, ferrocene, polyethyleneimine (PEI), and Bletilla striata polysaccharide (BSP), through multiple non-covalent interactions, which can intelligently release BSP by recognizing the wound inflammatory microenvironment through the cyclodextrin-ferrocene unit. Moreover, the porosity (65 % - 85 %), Young's modulus (400 KPa - 140 KPa), and DPPH scavenge rate (18 % - 40 %) of the hydrogel are modulated by varying the BSP content. The hydrogel exhibits outstanding antibacterial properties (98.3 % reduction of Escherichia coli observed after exposure to HTFC@BSP-20 for 24 h) and favorable biocompatibility. Furthermore, in a rat full-thickness skin wound model, the dual-function hydrogel significantly accelerates wound healing, increased CD31 expression promotes vascular regeneration, reduced TNF-α express and inhibited the inflammation. This multifunctional ROS responsive hydrogel provides a new perspective for antibiotics-free treatment of skin injuries.

Fabrication and development of biogenic selenium nanoparticles incorporated alginate hydrogel wound care material: a pre-clinical study

ABSTRACT In this study, we attempted to make a nanocomposite wound dressing that was both interactive and bioactive. In order to characterize the biogenic selenium nanoparticles, characterization techniques such as SEM, EDX, DLS, Zetasizer, FTIR, and XRD were utilized. The XRD results showed that the peaks located at around 2θ = 23.9°, 30.1°, 41.6°, 44.1°, and 52.9° that are corresponded to the (100), (101), (110), (102), and (201) reflections of the pure hexagonal phase of selenium crystals. The results of zeta potential measurement showed that the biosynthesized SeNPs have a zeta potential of around −27.5 mV. Studies conducted on animals using a full-thickness wound model of the rat’s skin showed that the wound dressing was able to speed up the natural process of wound healing. Based on the findings, it was determined that the wound dressing has the potential to serve as an effective wound dressing and healing material.

Design And Characterization Of Regenerative Potential In Full Thickness Burn Wound Model

Hydrogel is a three-dimensional network of interconnecting polymers that is crosslinked and consists of hydrophilic polymers that can absorb and endure water. Because it mimics the extracellular matrix (ECM), the hydrogel has found widespread use in pharmacological and biological applications. Many types of wound dressings are based on hydrogels due to its many advantages. These dressings include Coseal, Tegaderm, Algisite, and Evicel. Notwithstanding their exceptional ability to cure wounds, they have many drawbacks, including expensive expenses, unfavourable storage conditions, and inadequate mechanical protection for the wound. As we have come to realise the need for dressings with greater performance qualities (e.g., antimicrobial, biodegradable, responsive, and injectable), the field of wound dressings has attracted an increasing amount of interest. The purpose of this work is to evaluate the hydrogel loaded with 7, 8-Dihydroxy flavone's healing capabilities in a full-thickness burn wound model.

Collagen-Heparin-FGF2-VEGF Scaffolds Induce a Regenerative Gene Expression Profile in a Fetal Sheep Wound Model

Background:The developmental abnormality spina bifida is hallmarked by missing tissues (e.g. skin) and exposure of the spinal cord to the amniotic fluid, which can negatively impact neurological development. Surgical closure of the skin in utero limits neurological damage, but in large defects this results in scarring and contractures. Stimulating skin regeneration in utero would greatly benefit treatment outcome. Previously, we demonstrated that a porous type I collagen (COL) scaffold, functionalized with heparin (HEP), fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor (VEGF) (COL-HEP/GF) improved pre- and postnatal skin regeneration in a fetal sheep full thickness wound model. In this study we uncover the early events associated with enhanced skin regeneration.Methods:We investigated the gene expression profiles of healing fetal skin wounds two weeks after implantation of the COL(-HEP/GF) scaffolds. Using laser dissection and microarrays, differentially expressed genes (DEG) were identified in the epidermis and dermis between untreated wounds, COL-treated wounds and wounds treated with COL-HEP/GF. Biological processes were identified using gene enrichment analysis and DEG were clustered using protein–protein-interaction networks.Results:COL-HEP/GF influences various interesting biological processes involved in wound healing. Although the changes were modest, using protein–protein-interaction networks we identified a variety of clustered genes that indicate COL-HEP/GF induces a tight but subtle control over cell signaling and extracellular matrix organization.Conclusion:These data offer a novel perspective on the key processes involved in (fetal) wound healing, where a targeted and early interference during wound healing can result in long-term enhanced effects on skin regeneration.

Evaluation of Full Thickness Wounds Following Application of a Visco-Liquid Hemostat in a Swine Model.

Wound healing is a complex dynamic biomechanical process as the body attempts to restore the integrity of traumatized or devitalized tissues. There are four stages of wound of healing that begins with hemostasis followed by inflammation, proliferation and finally weeks later wound remodeling. Full thickness wounds usually are covered with a dressing material after hemostasis, which allows for controlled hydration. We investigated the potential of a visco-liquid hemostat, polyhedral oligomeric silsesquioxane (POSS), for providing hemostasis and to maintain a microenvironment in the wound bed that would maintain moisture content and promote early re-epithelialization. We hypothesized that the hemostatic agent POSS if left in the wound bed would maintain a protective barrier and accelerate wound healing similar to using saline to irrigate the wound to keep the wound moist. We compared the early phase of wound repair (3-7 days) in a porcine full thickness wound model to evaluate the efficacy of the material. Biopsies were taken after 3 and 7 days to determine the acute response of the POSS hemostat or saline on inflammation, cell migration, concentrations of metalloproteinase (MMPs), and tissue inhibitors of metalloproteinase (TIMPs). Accelerated healing was observed in POSS treated wounds by changes in wound contraction, keratinocyte migration, and development of granulation tissue in comparison to saline treated wounds. Increased concentrations at day 3 of MMP-2, MMP-3, and in MMP-1 at day 7 in POSS treated wounds compared to saline coincide with keratinocyte migration observed in the tissue histology and changes in wound contraction. Tissue concentrations of TIMP-1 and TIMP-2 in POSS treated wounds appear to coordinate the sequence of MMP events in the healing tissue. Matrix metalloproteinase-13, a marker for tissue remodeling, was not upregulated in the early wound healing cascade in either POSS or saline treated wounds at 3 or 7 days. Overall, the data suggests POSS treatment contributed to enhanced early cell migration and wound closure compared to saline treatment.

The stress-responsive gene ATF3 drives fibroblast activation and collagen production through transcriptionally activating TGF-β receptor Ⅱ in skin wound healing

Skin wound is an emerging health challenge on account of the high-frequency trauma, surgery and chronic refractory ulcer. Further study on the disease biology will help to develop new effective approaches for wound healing. Here, we identified a wound-stress responsive gene, activating transcription factor 3 (ATF3), and then investigated its biological action and mechanism in wound healing. In the full-thickness skin wound model, ATF3 was found to promote fibroblast activation and collagen production, resulted in accelerated wound healing. Mechanically, ATF3 transcriptionally activated TGF-β receptor Ⅱ via directly binding to its specific promoter motif, followed by the enhanced TGF-β/Smad pathway in fibroblasts. Moreover, the increased ATF3 upon skin injury was partly resulted from hypoxia stimulation with Hif-1α dependent manner. Altogether, this work gives novel insights into the biology and mechanism of stress-responsive gene ATF3 in wound healing, and provides a potential therapeutic target for treatment.