Stages Of Wound Healing Research Articles

Crocin-1 laden thermosensitive chitosan-based hydrogel with smart anti-inflammatory performance for severe full-thickness burn wound therapeutics

Burns are the fourth most common type of civilian trauma worldwide, and the management of severe irregular scald wounds remains a significant challenge. Herein, crocin-1 laden hydroxybutyl chitosan (CRO-HBC) thermosensitive hydrogel with smart anti-inflammatory performance was developed for accelerating full-thickness burn healing. The injectable and shape adaptability of the CRO-HBC gel make it a promising candidate for effectively filling scald wounds with irregular shapes, while simultaneously providing protection against external pathogens. The CRO-HBC gel network formed by hydrophobic interactions exhibited an initial burst release of crocin-1, followed by a gradual and sustained release over time. The excessive release of ROS and pro-inflammatory cytokines should be effectively regulated in the early stage of wound healing. The controlled release of crocin-1 from the CRO-HBC gel adequately addresses this requirement for wound healing. The CRO-HBC hydrogel also exhibited an excellent biocompatibility, an appropriate biodegradability, keratinocyte migration facilitation properties, and a reactive oxygen species scavenging capability. The composite CRO-HBC hydrogel intelligently mitigated inflammatory responses, promoted angiogenesis, and exhibited a commendable efficacy for tissue regeneration in a full-thickness scalding model. Overall, this innovative temperature-sensitive CRO-HBC injectable hydrogel dressing with smart anti-inflammatory performance has enormous potential for managing severe scald wounds.

WOUND DRESSINGS FOR SORPTION THERAPY IN THE TREATMENT OF PURULENT WOUNDS: a review article

Surgical infections remain one of the most challenging and urgent issues in modern medicine, reaching a socio-ecological scale of significance nationwide. Despite advances in treating purulent wounds, the prevalence of patients with purulent surgical infections remains high. According to both domestic and international sources, surgical patients with purulent-inflammatory conditions comprise 35–45% of the total patient population in general surgery wards. In some cases, purulent infections become acute and can lead to the generalization of the purulent process, resulting in sepsis and even death. Mortality rates from acute surgical infections range from 19% to 70% within surgical hospitals. Additionally, there has been an increase in the transition of acute purulent processes to chronic stages, which prolongs the treatment duration for these patients. The prevention and treatment of surgical infections are therefore of paramount importance, representing one of the core challenges in surgical care. Optimal local treatment of purulent wounds requires adherence to essential principles, including active surgical intervention, antibiotic therapy throughout the wound healing stages, and local wound management under bandages. An analysis of the literature reveals that sorption-application therapy is gaining prominence in modern surgical practice for local wound management. This approach, which utilizes advanced interactive wound dressings with combined adsorption, osmotic, and necrolytic effects, has shown significant improvements in the effectiveness of purulent wound treatment.

A Dry Patch with In Situ Solid-to-Gel Transformation for All-in-One Skin Wound Care.

Hydrogel-based dressing materials offer significant potential in expediting skin wound healing. Nevertheless, they face several challenges: poor adhesion to wound tissues, difficulties in preservation under ambient conditions, and limited multifunctionality to support all wound healing stages. In this work, a dry patch is designed to address these persistent issues by featuring an in situ solid-to-gel transformation and Janus wet tissue adhesiveness. The HGP patch integrates a wet adhesive layer combining dopamine-conjugated hyaluronic acid (HD) and poly(acrylic acid) (PAA), a drug-loading layer comprising gelatin (Gel), and a nonadhesive gelation layer of poly(vinyl alcohol) (PVA) and sodium alginate (SA). This hierarchical structural design confers exceptional wound adhesion, hemostatic capabilities, and antibacterial and antioxidant activities, as well as immune regulatory properties. These attributes collectively support accelerated skin wound healing, particularly in cases complicated by bacterial infections. This research charts an approach to engineer hydrogel-based wound dressings through on-site hydrogel formation, thus advancing the treatment of wounds afflicted with complex infections.

Neutrophil Migration is a Crucial Factor in Wound Healing and the Pathogenesis of Diabetic Foot Ulcers: Insights into Pharmacological Interventions.

Diabetic foot ulcers (DFUs) pose a significant clinical challenge, characterized by impaired wound healing, chronic inflammation, and increased risk of infection. Neutrophils, as critical components of the innate immune response, play a pivotal role in the initial stages of wound healing, particularly during the inflammatory phase. This review explores the intricate relationship between neutrophil migration, inflammation, and the pathogenesis of DFU and drugs that can impact neutrophil production and migration. Neutrophils contribute to infection control through phagocytosis and release pro-inflammatory cytokines and reactive oxygen species, which, when dysregulated, can impede the wound healing process. Furthermore, the chronic hyperglycemic state characteristic of diabetes mellitus has been implicated in impairing neutrophil functions, including chemotaxis and oxidative burst. This compromised neutrophil response prolongs the inflammatory phase and disrupts the delicate balance required for efficient wound healing. Neutrophil extracellular traps (NETs), a unique form of neutrophil defence, have also been implicated in DFU pathogenesis, potentially exacerbating inflammation and tissue damage. Understanding the intricate interplay between neutrophil migration, dysregulated inflammatory responses, and hyperglycemia-driven impairments is essential for developing targeted therapeutic strategies for DFUs. This review sheds light on the critical role of neutrophils in DFU pathogenesis, and innovative and advanced treatment strategies for DFU, highlighting the potential for novel interventions to restore the balance between pro-inflammatory and wound healing processes, ultimately improving clinical outcomes for individuals with DFU.

Graphene-Based Wound Dressings for Wound Healing: Mechanism, Technical Analysis, and Application Status.

The development of novel wound dressings is critical in medical care. Graphene and its derivatives possess excellent biomedical properties, making them highly suitable for various applications in medical dressings. This review provides a comprehensive technical analysis and the current application status of graphene-based medical dressings. Initially, we discuss the chemical structure and the fabrication method of graphene and its derivatives. We then provide a detailed summary of the mechanisms by which graphene materials promote wound repair across the four stages of wound healing. Subsequently, we categorize the types of graphene-based wound dressings and analyze corresponding characteristics. Finally, we analyze the challenges encountered at present and propose solutions regarding future development trends. This paper aims to serve as a reference for further research in skin tissue engineering and the development of innovative graphene-based medical dressings.

Emerging Technological Advancement for Chronic Wound Treatment and Their Role in Accelerating Wound Healing.

Chronic wounds are a major healthcare burden and may severely affect the social, mental, and economic status of the patients. Any impairment in wound healing stages due to underlying factors leads to a prolonged healing time and subsequently to chronic wounds. Traditional approaches for the treatment of chronic wounds include dressing free local therapy, dressing therapy, and tissue engineering based scaffold therapies. However, traditional therapies need improvisation and have been advanced through breakthrough technologies. The present review spans traditional therapies and further gives an extensive account of advancements in the treatment of chronic wounds. Cutting edge technologies, such as 3D printing, which includes inkjet printing, fused deposition modeling, digital light processing, extrusion-based printing, microneedle array-based therapies, gene therapy, which includes microRNAs (miRNAs) therapy, and smart wound dressings for real time monitoring of wound conditions through assessment of pH, temperature, oxygen, moisture, metabolites, and their use for planning of better treatment strategies have been discussed in detail. The review further gives the future direction of treatments that will aid in lowering the healthcare burden caused due to chronic wounds.

Drug conjugates crosslinked bioresponsive hydrogel for combination therapy of diabetic wound

Basic fibroblast growth factor (bFGF) has proved to be effective for wound healing, yet its effectiveness is extremely retarded in diabetic wounds due to the severe oxidative stress in wound beds. To solve this issue, herein a novel combination therapy of bFGF and N-acetylcysteine (NAC, antioxidant) was devised for improved diabetic wound repair. To avoid rapid loss of both drugs in the wound beds, a bioresponsive hydrogel (bFGF-HSPP-NAC) was engineered by incorporating bFGF and NAC into polymer-drug conjugates (HSPP) via thiol-disulfide exchange reactions. In response to oxidative stress (e.g., reactive oxygen species), the disulfide bonds (SS) within the hydrogel are broken into thiol groups (-S-H), thereby promoting hydrogel degradation and enabling controlled drug release. Initially, NAC is released to scavenge free radicals and ameliorate oxidative damage. Subsequently, bFGF is released to expedite tissue regeneration. This combinatorial strategy is tailored to the specific characteristics of the wound microenvironment at various stages of diabetic wound healing, thereby achieving therapeutic efficacy. The results indicate that the bFGF-HSPP-NAC hydrogel markedly enhances re-epithelialization, collagen deposition, hair follicle regeneration, and neovascularization. In conclusion, the bioresponsive bFGF-HSPP-NAC hydrogel demonstrates significant potential for application in combinatorial therapeutic approaches for diabetic wound healing.

Multifunctional Carbon Dots Derived from Human Hair for Fast Healing Wounds Together with Oleogels

In the complex process of wound healing, oleogels (OG) are suitable as the primary component of dressing materials, but they cannot meet the diverse requirements at different healing stages. In this study, a new kind of carbon dots (CrCi‐CDs) prepared by carbonizing human hair, exhibits excellent hemostatic, antibacterial, anti‐inflammatory, and pro‐angiogenic properties and thus supports the various stages of wound healing effectively. Such CrCi‐CDs are incorporated into OG to produce a CrCi‐CD/OG composite material with enhanced multifunctional capabilities, significantly outperforming OG alone. Various experiments in vitro and in vivo confirm that the CrCi‐CDs/OG can rapidly achieve hemostasis at the initial stage of wound formation, subsequently inhibit bacterial proliferation and biofilm formation, improve the complex microenvironment surrounding the wound, and promote neovascularization, ultimately accelerating the wound repair.

Absence of Langerhans cells resulted in over-influx of neutrophils and increased bacterial burden in skin wounds

Langerhans cells (LCs) are resident dendritic cells in the epidermis and their roles in presenting antigens derived from microorganisms present in the skin has been well appreciated. However, it is generally thought that incoming neutrophils are mainly responsible for eradicating invading pathogens in the early stage of wounds and a role of LCs in innate immunity is elusive. In the current study, we showed that wounds absent of LCs had a delayed closure. Mechanistically, LCs were the primary cells in warding off bacteria invasion at the early stage of wound healing. Without LCs, commensal bacteria quickly invaded and propagated in the wounded area. keratinocytes surrounding the wounds responded to the excessive bacteria by elevated production of CXCL5, resulting in an over-influx of neutrophils. The over-presence of activated neutrophils, possibly together with the aggravated invasion of bacteria, was detrimental to epidermal progenitor cell propagation and re-epithelialization. These observations underscore an indispensable role of LCs as effective guardians that preclude both bacteria invasion and damages inflicted by secondary inflammation.

Dandelion-shaped strontium-gallium microparticles for the hierarchical stimulation and comprehensive regulation of wound healing.

The management of full-thickness skin injuries continues to pose significant challenges. Currently, there is a dearth of comprehensive dressings capable of integrating all stages of wound healing to spatiotemporally regulate biological processes following full-thickness skin injuries. In this study, we report the synthesis of a dandelion-shaped mesoporous strontium-gallium microparticle (GE@SrTPP) achieved through dopamine-mediated strontium ion biomineralization and self-assembly, followed by functionalization with gallium metal polyphenol networks. As a multifunctional wound dressing, GE@SrTPP can release bioactive ions in a spatiotemporal manner akin to dandelion seeds. During the early stages of wound healing, GE@SrTPP demonstrates rapid and effective hemostatic performance while also exhibiting antibacterial properties. In the inflammatory phase, GE@SrTPP promotes M2 polarization of macrophages, suppresses the expression of pro-inflammatory factors, and decreases oxidative stress in wounds. Subsequently, during the stages of proliferation and tissue remodeling, GE@SrTPP facilitates angiogenesis through the activation of the Hypoxia-inducible factor-1α/vascular endothelial growth factor (HIF-1α/VEGF) pathway. Analogous to the dispersion and rooting of dandelion seeds, the root-like new blood vessels supply essential nutrients for wound healing. Ultimately, in a rat chronic wound model, GE@SrTPP achieved successful full-thickness wound repair. In summary, these dandelion-shaped GE@SrTPP microparticles demonstrate comprehensive regulatory effects in managing full-thickness wounds, making them highly promising materials for clinical applications.

SFRP2 modulates functional phenotype transition and energy metabolism of macrophages during diabetic wound healing.

Diabetic foot ulcer (DFU) is a serious complication of diabetes mellitus, which causes great health damage and economic burden to patients. The pathogenesis of DFU is not fully understood. We screened wound healing-related genes using bioinformatics analysis, and full-thickness skin injury mice model and cellular assays were used to explore the role of target genes in diabetic wound healing. SFRP2 was identified as a wound healing-related gene, and the expression of SFRP2 is associated with immune cell infiltration in DFU. In vivo study showed that suppression of SFRP2 delayed the wound healing process of diabetic mice, impeded angiogenesis and matrix remodeling, but did not affect wound healing process of control mice. In addition, suppression of SFRP2 increased macrophage infiltration and impeded the transition of macrophages functional phenotypes during diabetic wound healing, and affected the transcriptome signatures-related to inflammatory response and energy metabolism at the early stage of wound healing. Extracellular flux analysis (EFA) showed that suppression of SFRP2 decreased mitochondrial energy metabolism and increased glycolysis in injury-related macrophages, but impeded both glycolysis and mitochondrial energy metabolism in inflammatory macrophages. In addition, suppression of SFRP2 inhibited wnt signaling-related genes in macrophages. Treatment of AAV-SFRP2 augmented wound healing in diabetic mice and demonstrated the therapeutic potential of SFRP2. In conclusions, SFRP2 may function as a wound healing-related gene in DFU by modulating functional phenotype transition of macrophages and the balance between mitochondrial energy metabolism and glycolysis.

7877 Adipose Depot Differences In Regenerative Properties Of Exosomes Derived From Human Adipose Stem Cells

Abstract Disclosure: M.A. Krause-Hauch: None. R. Patel: None. B. Osborne: None. P. Albear: None. N.A. Patel: None. Many patients struggle with chronic recalcitrant wounds that are the result of delayed healing. Underlying inflammation is one major risk factor for impaired dermal wound healing that may lead to pathologies such as infection and scarring. Adult human adipose stem cells (hASCs) have shown tremendous potential in regenerative medicine. The regenerative potential of hASCs is dependent on secreted bioactive material which is packaged and released in extracellular exosomes. We previously showed that hASC exosomes from the subcutaneous depot (sc) promoted repair in human dermal fibroblasts using in vitro assays. In this study, we evaluated exosomes derived from the omental depot (om) of hASC and compared its efficacy with sc-hASC. Our results show differences in levels of the long noncoding RNA (lncRNA) cargo between om-hASCexo and sc-hASCexo. Next, we evaluated their repair potential in a wound model in vivo. Male and female F344 rats were dorsally wounded via punch biopsy and silicone scaffolding was attached to prevent contraction. The wounds were then either not treated (control) or treated with 50μg om-hASCexo or sc-hASCexo every alternate day when each wound size was measured for 1 week to monitor healing progress. After 7 days, wounds treated with either om-hASCexo and sc-hASCexo closed significantly faster than untreated control wounds. While no difference was observed in closure percentage after 7 days for wounds treated with either om-hASCexo and sc-hASCexo, sc-hASCexo appeared to act faster earlier (1-2 days post wound) in the wound healing process while om-hASCexo acts faster during later stages (2-4 days post wound) of wound healing. The wound tissue was collected for biochemical and histological analysis. qPCR analysis on day 7 revealed that both om-hASCexo and sc-hASCexo treatment resulted in increased levels of Collagen 1 & 3 and MMP9, while levels of TGF-β decreased with treatment. These results indicate that om-hASCexo and sc-hASCexo enhanced the wound healing process while decreasing inflammation of the wound. To determine the differences between om-hASCexo and sc-hASCexo treatments on wound healing pathways, RNAseq was performed. Results show specificity in pathway activation and gene expression between the om-hASCexo and sc-hASCexo treatments. In conclusion, we have demonstrated that the regenerative mechanisms differ between the hASC depots from which exosomes are secreted. At a broader level, this finding may shed light on the body’s organ health and repair processes in normal or disease states. Presentation: 6/3/2024

Skin organoid transplantation promotes tissue repair with scarless in frostbite.

Frostbite is the most common cold injury and is caused by both immediate cold-induced cell death and the gradual development of localized inflammation and tissue ischemia. Delayed healing of frostbite often leads to scar formation, which not only causes psychological distress but also tends to result in the development of secondary malignant tumors. Therefore, a rapid healing method for frostbite wounds is urgently needed. Herein, we used a mouse skin model of frostbite injury to evaluate the recovery process after frostbite. Moreover, single-cell transcriptomics was used to determine the patterns of changes in monocytes, macrophages, epidermal cells and fibroblasts during frostbite. Most importantly, human-induced pluripotent stem cell (hiPSC) -derived skin organoids combining with gelatin-hydrogel were constructed for the treatment of frostbite. The results showed that skin organoid treatment significantly accelerated wound healing by reducing early inflammation after frostbite and increasing the proportions of epidermal stem cells. Moreover, in the later stage of wound healing, skin organoids reduced the overall proportions of fibroblasts, significantly reduced fibroblast-to-myofibroblast transition by regulating the integrin α5β1-FAK pathway, and remodeled the extracellular matrix (ECM) through degradation and reassembly mechanisms, facilitating the restoration of physiological ECM and reducing the abundance of ECM associated with abnormal scar formation. These results highlight the potential application of organoids for promoting the reversal of frostbite-related injury and the recovery of skin functions. This study provides a new therapeutic alternative for patients suffering from disfigurement and skin dysfunction caused by frostbite.

Tailor-made curdlan based nanofibrous dressings enable diabetic wound healing

The development and application of novel polysaccharides that can improve diabetic wound healing is crucial. Dressings containing curdlan have the potential to promote healing in diabetic wounds, but the underlying mechanism remain unclear. In addition, the functional modifications that could further enhance the activity of curdlan in promoting diabetic wound healing have not been explored. Herein, we investigated the capabilities of curdlan (CU) and its four derivatives i.e., sulfated curdlan (SC), amino-curdlan (AC) carboxymethyl curdlan (CMC) and CMC/ZnO nanocomposites for diabetic wound healing. Pristine CU and its derivatives were blended with polyvinyl alcohol (PVA) to fabricate electrospun nanofiber dressings (ENDs) with uniform appearances. The PVA/CU, PVA/CMC and PVA/CMC-ZnO ENDs were more compatible with keratinocytes, fibroblasts, and macrophages than that of PVA/AC ENDs. Notably, PVA/CMC ENDs and PVA/CMC-ZnO ENDs exhibited superior wound healing efficiencies than other ENDs. Among various dressings, PVA/CU, PVA/SC, PVA/CMC ENDs effectively reduced M1 macrophages and facilitated M2 phenotype at early stage of diabetic wound healing. Collectively, the PVA/CMC ENDs demonstrated greater therapeutic potential against diabetic wounds compared to other modified scaffolds via regulating macrophage polarization.

Glucose-activated self-cascade antibacterial and pro-angiogenesis nanozyme-functionalized chitosan-arginine thermosensitive hydrogel for chronic diabetic wounds healing

Affected by persistent hyperglycemia, diabetic neuropathy, and vasculopathy hinder the progression of wound healing by exacerbating susceptibility to recurrent bacterial infection and impairing vascularization. In order to cater to the requirements of diabetic chronic wound healing at various stages, we designed an antibacterial and pro-angiogenic wound dressing with localized glucose-lowering capacity. In this study, we constructed a copper-based metal-organic framework (MOF) nanozyme and loaded with glucose oxidase (GOX) to prepare Cu-MOF/GOX, which was subsequently integrated with CS-Arg (chitosan modified by L-Arginine) and Pluronic (F127) to fabricate multifunctional Cu-MOF/GOX-Gel thermosensitive hydrogel. The GOX generated H2O2 (hydrogen peroxide) and gluconic acid by consuming high blood glucose at the wound site, thus initiating an efficient antibacterial self-cascade catalytic in the initial stages of wound healing. With the further catalysis of in situ generated H2O2, NO (nitric oxide) was gradually released from the hydrogel, facilitating angiogenesis and accumulation of collagen, thereby expediting subsequent phases of wound healing. Overall, the Cu-MOF/GOX-Gel exhibits a comprehensive ability to locally regulate blood glucose levels, while also synergistically promoting antibacterial activity and angiogenesis, that effectively chronic diabetic wounds healing.

An Advanced Hydrogel Dressing System with Progressive Delivery and Layer-to-Layer Response for Diabetic Wound Healing

Wound healing in diabetic patients presents a significant challenge due to delayed inflammatory responses, which obstruct subsequent healing stages. In response, we have developed a progressive, layer-by-layer responsive hydrogel, specifically designed to meet the dynamic requirements of diabetic wounds throughout different healing phases. This hydrogel initiates with a glucose-responsive layer formed by boronate ester bonds between 4-arm-poly (ethylene glycol) succinimidyl glutarate (4arm-PEG-SG) and 3-aminophenylboronic acid. This configuration ensures precise control over the physicochemical properties, facilitating accurate drug release during the healing process. Furthermore, we have incorporated an active pharmaceutical ingredient ionic liquid (API) composed of diclofenac and L-carnitine. This combination effectively tackles the solubility and stability issues commonly associated with anti-inflammatory drugs. To further refine drug release, we integrated matrix metalloproteinase-9 (MMP-9)-sensitive gelatin microcapsules, ensuring a controlled release and preventing the abrupt, uneven drug distribution often seen in other systems. Our hydrogel's rheological properties closely resemble human skin, offering a more harmonious approach to diabetic wound healing. Overall, this progressive layer-by-layer responsive wound management system, which is a safe, efficient, and intelligent approach, holds significant potential for the clinical treatment of diabetic wounds. Statement of SignificanceThe two main problems of diabetic wounds are the long-term infiltration of inflammation and the delayed repair process. In this experiment, a glucose-responsive hierarchical drug delivery system was designed to intelligently adjust gel properties to meet the needs of inflammation and repair stage of wound healing, accelerate the transformation of inflammation and repair stage, and accelerate the process of repair stage. In addition, in order to achieve accurate drug release in anti-inflammatory layer hydrogels and avoid sudden drug release due to poor solubility of anti-inflammatory small molecule drugs, we constructed a ionic liquid of active pharmaceutical ingredients (API-ILs) using diclofenac and L-carnitine as raw materials. It was wrapped in MMP-9 enzyme active gelatin microcapsule to construct a double-reaction anti-inflammatory layer gel to achieve accurate drug release. These findings highlight the potential of our system in treating diabetic wounds, providing a significant advance in wound treatment.

Alpha(α)-mangostin (Xanthone of Garcinia mangostana L.): Augmenting Macrophages Activity for an Effective Diabetic Wound Healing

Diabetic wounds are particularly difficult to treat medically because they heal at a slower pace than regular wounds. Macrophages are essential in all stages of normal wound healing, including inflammation, proliferation and rem odelling. When wound healing is affected, macrophages can reduce the level of growth factor and increase the level of interleukin-6 (IL-6), disrupt the balance between tissue inhibitors of metalloproteinase (TIMPs) and matrix metalloproteinase (MMPs), which can slow down healing. Alpha(α)-mangostin, a natural xanthone derived from the pericarp of the mangosteen, has gained considerable attention due to its anti-inflammatory properties, suggesting its potential to promote wound healing. However, its exact role in healing diabetic foot ulcers, common in diabetes, remains unclear. Hence, this study aims to explore how α-mangostin might affect diabetic wound healing by evaluating its impact on PDGF, CTGF, BFGF, VEGF, TGF-β, MMP-9, TIMP-2 and IL-6 secretion in macrophage cells. Human monocytic macrophages (THP-1) were incubated with a 35 mM glucose solution for 72 h to create a glucose-enriched medium. The cells were then incubated with α-mangostin (0.15, 2.5 and 5 µg/mL) together with 35 mM glucose. Carboxymethyl cellulose (CMC) served as positive controls; glucose-enriched media and media-alone served as negative controls. Protein expression was measured using ELISA. α-mangostin (2.5 µg/mL) increased the levels of PDGF and VEGF and decreased the level of MMP-9 compared to glucose controls. There was no significant difference in other growth factors, TIMP-2 and IL-6 protein levels across any of the treatment groups compared to glucose controls. In conclusion, α-mangostin particularly at 2.5 µg/mL demonstrated a significant increase in PDGF and VEGF levels while simultaneously reducing MMP-9 in macrophage cells under glucose-induced conditions. These findings suggest that α-mangostin holds the potential for enhancing the healing of chronic wounds in diabetic conditions. HIGHLIGHTS Treatment of macrophages (THP-1 cells) with 2.5 µg/mL Alpha (α)-mangostin in a high glucose medium led to a significant increase in PDGF and VEGF secretion compared to glucose control. Treatment of the cells with 2.5 µg/mL Alpha (α)-mangostin in a high glucose medium led to a significant reduction of MMP-9 secretion compared to glucose control. There is no significant effects of Alpha (α)-mangostin on IL-6 and TIMP secretion compared to controls This study suggests that Alpha (α)-mangostin may be beneficial in promoting diabetic wound healing via stimulation of PDGF and VEGF secretion and reducing MMP-9 levels. GRAPHICAL ABSTRACT

Exosomes and microRNAs: insights into their roles in thermal-induced skin injury, wound healing and scarring.

A burn is a type of injury to the skin or other tissues caused by heat, chemicals, electricity, sunlight, or radiation. Burn injuries have been proven to have the potential for long-term detrimental effects on the human body. The conventional therapeutic approaches are not able to effectively and easily heal these burn wounds completely. The main potential drawbacks of these treatments include hypertrophic scarring, contracture, infection, necrosis, allergic reactions, prolonged healing times, and unsatisfactory cosmetic results. The existence of these drawbacks and limitations in current treatment approaches necessitates the need to search for and develop better, more efficient therapies. The regenerative potential of microRNAs (miRNAs) and the exosomal miRNAs derived from various cell types, especially stem cells, offer advantages that outweigh traditional burn wound healing treatment procedures. The use of multiple types of stem cells is gaining interest due to their improved healing efficiency for various applications. Stem cells have several key distinguishing characteristics, including the ability to promote more effective and rapid healing of burn wounds, reduced inflammation levels at the wound site, and less scar tissue formation and fibrosis. In this review, we have discussed the stages of wound healing, the role of exosomes and miRNAs in improving thermal-induced wounds, and the impact of miRNAs in preventing the formation of hypertrophic scars. Research studies, pre-clinical and clinical, on the use of different cell-derived exosomal miRNAs and miRNAs for the treatment of thermal burns have been documented from the year 2000 up to the current time. Studies show that the use of different cell-derived exosomal miRNAs and miRNAs can improve the healing of burn wounds. The migration of exosomal miRNAs to the site of a wound leads to inhibition of apoptosis, induction of autophagy, re-epithelialization, granulation, regeneration of skin appendages, and angiogenesis. In conclusion, this study underscores the importance of integrating miRNA and exosome research into treatment strategies for burn injuries, paving the way for novel therapeutic approaches that could significantly improve patient outcomes and recovery times.

Amorphous zinc phosphate nanoclusters loaded polycarbonate thermosensitive hydrogel: An innovative strategy for promoting wound healing

Skin trauma is a matter of great concern for public health, emphasizing the importance of reconstructing the microenvironment at the trauma site to facilitate tissue regeneration. Therefore, the investigation of innovative wound dressings has significant research and clinical implications. In this study, we prepared a thermosensitive hydrogel based on a hydrophilic-hydrophobic-hydrophilic triblock polycarbonate polymer (PTP), and created a composite hydrogel, PTPH-AZP, by incorporating amorphous zinc phosphate (AZP) nanoclusters. We evaluated the effects of PTPH-AZP on human umbilical vein endothelial cells (HUVECs) and the ability to promote skin wound healing. According to the results, PTPH-AZP was found to promote the proliferation, migration, and tube formation of HUVECs through the sustained release of Zn2+ at appropriate concentrations. In vivo experiments demonstrated that in the early-mid stages of wound healing, PTPH-AZP promotes increases in Platelet Endothelial Cell Adhesion Molecule-1 (CD31) and α-Smooth Muscle Actin (α-SMA) content within the wound area, facilitating accelerated re-epithelialization and enhanced collagen deposition. In later healing stages, epidermal thickness in the PTPH-AZP treated group was significantly improved, aligning with surrounding intact skin with no instances of attenuated or hypertrophic scarring observed. The findings from the in vivo study suggested that PTPH-AZP may have a positive impact on vascularization and wound healing. In conclusion, this study presents a promising strategy for skin wound healing, highlighting the potential of PTPH-AZP as an effective therapeutic approach.

Radial Egg White Hydrogel Releasing Extracellular Vesicles for Cell Fate Guidance and Accelerated Diabetic Skin Regeneration.

Topology and bioactive molecules are crucial for stimulating cellular and tissue functions. To regulate the chronic wound microenvironment, mono-assembly technology is employed to fabricate a radial egg white hydrogel loaded with lyophilized adipose tissue-extracellular vesicles (radial EWH@L-EVs). The radial architecture not only significantly modified the gene expression of functional cells, but also achieved directional and controlled release kinetics of L-EVs. Through the synergy of topographical and inherent bioactive cues, radial EWH@L-EVs effectively reduced intracellular oxidative stressand promoted the polarization of macrophages toward an anti-inflammatory phenotype during the inflammatory phase. Afterward, radial EWH@L-EVs facilitated the centripetal migration and proliferation of fibroblasts and endothelial cells as the wound transitioned to the proliferative phase. During the latter remodeling phase, radial EWH@L-EVs accelerated the regeneration of granulation tissue, angiogenesis, and collagen deposition, thereby promoting the reorganization chronic wound. Compared with the gold standard collagen scaffold, radial EWH@L-EVs actively accommodated the microenvironment via various functions throughout all stages of diabetic wound healing. This can be attributed to the orientation of topological structures and bioactive molecules, which should be considered of utmost importance in tissue engineering.