Improve Wound Healing Research Articles

Determination Of Total Alkaloid Content Of Chinese Betel (Peperomia pellucida) Based On Differences In Ethanol Concentration Using Uv-Vis Spectrophotometry Method

Background: The Chinese betel plant (Peperomia pellucida) is used by the community as a potential plant because it contains many benefits, one of which contains alkaloid compounds. Alkaloids have the ability to help heal wounds because the active compounds contained in alkaloids have antioxidant activity so that improved wound healing by Chinese betel plants (Peperomia pellucida) can be caused by the action of free radicals in increasing levels of antioxidant enzymes. This research will use the maceration extraction method using 70% ethanol and 96% ethanol solvents which will be carried out using the UV-Vis spectrophotometric method.Objective: Determine differences in alkaloid levels of Chinese betel (Peperomia pellucida) based on differences in ethanol.Methods: This study is an experimental study. The dependent variable is the total alkaloid content of Chinese betel, while the independent variable is the difference in ethanol concentration.Results: Alkaloid levels in each ethanol, namely, in 70% ethanol it was 21,11%, and in 96% ethanol it was 42,413%. From these results it can be seen that the highest alkaloid levels are found in the 96% ethanol extract.Conclusion: There are differences in results between 70% ethanol extract and 96% ethanol extract.

Early results of an orthoplastic multidisciplinary approach to diabetic foot ulcer soft tissue reconstruction.

Diabetic foot ulcer (DFU) is a common complication in patients with diabetes. With current treatment, only two-thirds of patients heal, with a median duration of 3-6 months. Hard-to-heal DFUs are a major source of morbidity and mortality. Improving wound healing via soft tissue reconstruction may be the key to improving clinical outcomes. Thus, the Diabetic Limb Salvage (DLS) service in Sengkang General Hospital, Singapore, was established to provide patients with a streamlined, one-stop, comprehensive service dedicated to DFU soft tissue reconstruction. The reconstruction was carried out using secondary closure, skin grafting, local flaps or free flaps, depending on the severity of the wound and patient suitability. This study aims to audit the early outcomes of the DLS service. Patients with DFUs treated by the DLS service were compared with patients with DFUs treated prior to the launch of the DLS service (control). Outcomes including major and minor amputation rates, wound healing rate, mortality and DFU recurrence rates were analysed statistically. A total of 103 patients took part in the study (50 in the DLS service cohort and 50 in the control cohort). There was no significant difference in demographics, comorbidities and wound profiles between the two cohorts. All (100%) patients in the DLS service cohort received soft tissue reconstruction versus only 13% in the control group. The DLS service cohort had a significantly higher healing rate (96% versus 68%, respectively), shorter healing duration (77±30 days versus 111±43 days, respectively), reduced major amputation rate (0% versus 9%, respectively), and reduced recurrence rate (6% versus 25%, respectively) compared with the control cohort within the one-year follow-up. The findings of this study showed that an orthoplastic multidisciplinary approach focused on DFU soft tissue reconstruction improved wound healing rates, shortened healing duration and, as a result, lowered amputation rates and reduced recurrence.

АМАРАНТ ЯК ДЖЕРЕЛО ВТОРИННИХ МЕТАБОЛІТІВ З ПОТЕНЦІЙНОЮ РАНОЗАГОЮВАЛЬНОЮ АКТИВНІСТЮ

Amaranth is a multi-purpose crop, known for its wound-healing properties. Amaranth leaves and seeds contain polyphenols and flavonoids that improve wound healing. Ethanol extracts of amaranth seeds of “Lera” and “Ultra” varieties and ethanol extract of leafs Amaranthus retroflexus were obtained. Determination of the content of polyphenolic compounds in the extracts was conducted by the spectrophotometric method with the Folin-Checolteau reagent. The number of flavonoids in the extracts was determined by the spectrophotometric method using aluminum chloride.. The most polyphenolic compounds and flavonoids were found in the extract of leafs Amaranthus retroflexus. More polyphenols and flavonoids were found in the amaranth seed extract of the “Lera” variety than in the extract of the “Ultra” variety.

Deciphering the Interlinked CXCR4-Mediated Feedback Loop Among Signaling Pathways in Diabetic Wound Healing

Abstract: Diabetic chronic wounds and amputations are very serious complications of diabetes mellitus (DM) that result from an integration factor, including oxygen deprivation, elevated reactive oxygen species (ROS), reduced angiogenesis, and microbial invasion. These causative factors lead to tenacious wounds in an inflammatory state, which eventually results in tissue aging and necrosis. Wound healing in DM potentially targets C-X-C chemokine receptor type 4 (CXCR4) regulates several signalling pathways. The CXCR4 signalling pathway integrated with phospholipase C (PLC)/protein kinase-C (PKC) Ca2+ pathways, stromal cell-derived factor-1 (SDF-1), and mitogen- activated protein kinases (MAPKs) pathway for enhancing cell chemotaxis, proliferation, and survival. The dysregulated CXCR4 pathway is connected with poor wound healing in DM patients. Therapeutic strategies targeting CXCR4-based molecules such as UCUF-728, UCUF-965, and AMD3100 have been shown to enhance diabetic wound healing by altering miRNA expression, promoting angiogenesis, and accelerating wound closure. This study indicates that CXCR4 participation in various signalling pathways makes it essential for Understanding the healing of diabetic wounds. Using specific compounds to target CXCR4 offers a potentially effective treatment strategy to improve wound healing in diabetes. Our understanding of CXCR4 signalling and its regulation processes will enable us to develop more potent wound care solutions for diabetic chronic wounds. This report concludes that CXCR4's potential therapeutic targeting shows improvements in diabetic wound repair. This review will demonstrate that CXCR4 plays a major role in wound healing through its various signalling pathways. Targeting CXCR4 with certain agonist molecules shows a therapeutic approach to potentially increasing wound healing in diabetes. By enhancing our understanding of the CXCR4 signalling mechanism in future studies, we can develop more potential treatments for chronic diabetic wounds.

Preparation and characterization of Pistacia atlantica oleo-gum-resin-loaded electrospun nanofibers and evaluating its wound healing activity in two rat models of skin scar and burn wound.

A growing body of research is dedicated to developing new therapeutic agents for wound healing with fewer adverse effects. One of the proceedings being taken today in wound healing research is to identify promising biological materials that not only heal wounds but also vanish scarring. The effectiveness of nanofibers like polyvinyl alcohol (PVA), in improving wound healing can be related to their unique properties. Pistacia atlantica Desf. subsp. kurdica (Zohary) Rech. f. (PAK) [Anacardiaceae], also known as "Baneh" in traditional Iranian medicine, is one of the most effective herbal remedies for the treatment of different diseases like skin injuries due to its numerous pharmacological and biological properties, including anti-inflammatory, antioxidant, and anti-bacterial effects. Our study aimed to evaluate the wound-healing activity of nanofibers containing PVA/PAK oleo-gum-resin in two rat models of burn and excision wound repair. PVA/PKA nanofibers were prepared using the electrospinning method. Scanning electron microscope (SEM) images and mechanical properties of nanofibers were explored. Diffusion and releasing experiments of nanofibers were performed by the UV visible method at different time intervals and up to 72h. The animal models were induced by excision and burn in Wistar rat's skin and the wound surface area was measured during the experiment for 10 and 21days, respectively. On the last day, the wound tissue was removed for histological studies, and serum oxidative factors were measured to evaluate the antioxidant properties of the PVA/PKA. Data analysis was performed using ImageJ, Expert Design, and statistical analysis methods. PVA/PKA nanofibers were electrospun at different voltages (15, 18, and 20kV). The most suitable fibers were obtained when the nozzle was positioned 15cm away from the collector, with a working voltage of 15kV, and an injection rate of 0.5mm per hour, using the 30:70 w/v PKA gum. In the SEM images, it was found that the surface tension of the polymer solution decreased by adding the gum and yield thinner and longer fibers at a voltage of 15kV with an average diameter of 96 ± 24nm. The mechanical properties of PVA/PKA nanofibers showed that the presence of gum increased the tensile strength and decreased the tensile strength of the fibers simultaneously. In vivo results showed that PVA/PKA nanofibers led to a significant reduction in wound size and tissue damage (regeneration of the epidermal layer, higher density of dermal collagen fibers, and lower presence of inflammatory cells) compared to the positive (phenytoin and silver sulfadiazine) and negative control (untreated) groups. Wound contraction was higher in rats treated with PVA/PKA nanofibers. Additionally, antioxidative serum levels of catalase and glutathione were higher in the PVA/PKA nanofiber groups even in comparison to positive control groups. Pistacia atlantica oleo-gum-resin-loaded electrospun nanofibers potentially improve excision and burn models of skin scars in rats through antioxidative and tissue regeneration mechanisms.

A Versatile Skin-Derived Extracellular Matrix Hydrogel-Based Platform to Investigate the Function of a Mechanically Isolated Adipose Tissue Stromal Vascular Fraction.

Introduction: To accelerate cutaneous wound healing and prevent scarring, regenerative approaches such as injecting a mechanically derived tissue stromal vascular fraction (tSVF) are currently under clinical and laboratory investigations. The aim of our study was to investigate a platform to assess the interaction between skin-derived extracellular matrix (ECM) hydrogels and tSVF and their effects on their microenvironment in the first ten days of culture. Material and Methods: A tSVF mixed with ECM hydrogel was cultured for ten days. After 0, 3, 5, and 10 days of culture viability, histology, immunohistochemistry, gene expression, and collagen alignment and organization were assessed. Results: The viability analysis showed that tSVF remained viable during 10 days of culture and seemed to remain within their constitutive ECM. The fiber analysis demonstrated that collagen alignment and organization were not altered. No outgrowth of capillaries was observed in (immuno)histochemical staining. The gene expression analysis revealed that paracrine factors TGFB1 and VEGFA did not change and yet were constitutively expressed. Pro-inflammatory factors IL1B and IL6 were downregulated. Matrix remodeling gene MMP1 was upregulated from day three on, while MMP14 was upregulated at day three and ten. Interestingly, MMP14 was downregulated at day five compared to day three while MMP2 was downregulated after day zero. Conclusions: Skin-derived ECM hydrogels appear to be a versatile platform for investigating the function of a mechanically isolated adipose tissue stromal vascular fraction. In vitro tSVF remained viable for 10 days and sustained the expression of pro-regenerative factors, but is in need of additional triggers to induce vascularization or show signs of remodeling of the surrounding ECM. In the future, ECM-encapsulated tSVF may show promise for clinical administration to improve wound healing.

Hyperbaric oxygen treatment in addition to conventional multidisciplinary care in patients with calciphylaxis.

Calciphylaxis is a rare and serious complication in patients with kidney disease. It has few treatment options and poor prognosis. Hyperbaric oxygen therapy (HBOT) may improve wound healing and was added to our conventional care in 2012. Data from all calciphylaxis patients treated from 2012 to 2022 were retrieved from hospital records. HBOT was added to our multidisciplinary care of calciphylaxis, which included sodium-thiosulphate, dialysis if indicated, medical optimization of calcium-phosphate homeostasis, substitution of vitamin K2, withdrawal of warfarin, iron and vitamin D, and minimization of systemic steroids. In addition, weight- and nutritional status was optimized, and wound care was thoroughly performed. 25 patients received a total number of 1,493 HBOT treatments in addition to conventional care in the study period. Median HBOT per patient was 45 (range 1-267). One year after diagnosis, 18 out of 25 patients were alive. 15 out of the 18 patients alive 1 year after diagnosis had completely resolved wound lesions. Seven patients died within the first year after diagnosis due to cardiovascular disease (n=3), infection (n=3), and cancer (n=1). Our results suggest that HBOT is well-tolerated and may be associated with beneficial effects on survival and wound-healing when combined with multidisciplinary care.

Sulfated Galactan Derivative from Gracilaria fisheri Improves Histopathology and Alters Wound Healing-Related Proteins in the Skin of Excision Rats.

The biological activities of sulfated polysaccharides (SP) are well-documented, especially regarding wound healing. Sulfated galactan (SG), a type of SP extracted from the red seaweed Gracilaria fisheri, has been identified as having multiple therapeutic properties related to its wound healing capacity. Recent research indicates that degraded SG (DSG) from G. fisheri, when combined with octanoyl ester (DSGO), can improve wound healing in fibroblasts. However, the effectiveness of natural products in clinical settings often differs from in vitro results. This study aimed to develop and evaluate ointments containing DSG and DSGO for skin repair in an animal model. Twenty-four Wistar rats were divided into four groups: (1) normal control, (2) ointment control, (3) DSG ointment, and (4) DSGO ointment. After inducing full-thickness excision wounds, these ointments were applied to the wounds. Wound contraction rate, histopathology, and protein related wound healing expression were then elucidated. Our findings showed that both DSG and DSGO ointments significantly enhanced wound closure compared to the control groups. Histopathological and biochemical analyses indicated increased extracellular matrix production and fibroblasts, marked by improved fibroblast activity, neovascularization, and collagen deposition. Furthermore, immunohistochemistry and immunoblot analysis revealed that the ointments altered the expression of Ki67, α-smooth muscle actin (α-SMA), E-cadherin, vimentin, collagen, and components of the Smad signaling pathway, all of which are crucial for wound healing. The results also suggested that the DSGO ointment was marginally more effective in promoting wound healing in this model. These results indicate that ointment supplemented with DSG and DSGO have the potential to enhance skin repair by improving histopathology and altering wound healing-related proteins.

Schlafen5, regulated by the AP-1 family transcription factor c-Fos, affects diabetic wound healing through modulating PI3K/Akt/NRF2 axis

Diabetic ulcers (DUs) present significant physical and psychological challenges to patients, while placing a significant economic burden on healthcare systems. Promoting the blood vessel regeneration is critical for ensuring the delivery of essential nutrients and oxygen to the injured area, thereby supporting the healing process. To gain insight into the complex molecular mechanisms that drive DUs healing, we performed a comprehensive analysis of single-cell transcriptomic data from healing and non-healing DU states. This analysis revealed a key role of Schlafen5 (SLFN5) signal in modulating key healing processes. SLFN5, a protein known to regulate cellular processes like migration, invasion, inflammation, and cell death, emerged as an important player. Yet, although it is prominent, the specific function of SLFN5 in diabetic skin wounds remained unclear. Our study discovered a marked elevation of SLFN5 levels in endothelial cells within DUs and its suppression notably mitigates the oxidative stress and endoplasmic reticulum stress (ERS)-mediated cell death pathways, including pyroptosis and apoptosis. This finding implies that excessive SLFN5 activity might obstruct wound closure by intensifying cellular stress reactions. Upon further investigation, we found that the antioxidant and cytoprotective effects were mediated through enhanced NRF2 activity, facilitated by the PI3K/Akt signaling pathway. Moreover, our investigation identified that c-Fos as a pivotal transcription factor governing SLFN5 transcription during the development of DUs, offering valuable insights into the regulation of SLFN5 expression. In diabetic mice model, SLFN5 knockdown accelerating wound healing, which was intervened by PI3K/Akt inhibitor. These results hold significant therapeutic potential, indicating that targeting SLFN5 may represent a novel and effective strategy for improving wound healing outcomes in patients with DUs.

Spinal cord stimulation induces Neurotrophin-3 to improve diabetic foot disease.

Low-extremity ischemic disease is a common complication in diabetic patients, leading to reduced quality of life and potential amputation. This study investigated the therapeutic effect of spinal cord stimulation (SCS) on patients with diabetic foot disease and a rat model of diabetic foot injury. SCS was applied to patients with diabetic foot disease, with clinical assessments performed before and after therapy. Blood levels of NGF, BDNF, and NT-3 were determined by ELISA. A rat model of diabetic foot injury was established to validate NT-3's role in SCS therapy. SCS therapy improved the condition of patients with diabetic ischemic foot disease and promoted wound healing in the rat model. NT-3 levels significantly increased after SCS therapy in both patients and rats. Recombinant NT-3 administration improved wound healing and re-vascularization in the rat model, while NT-3 neutralization abrogated SCS's therapeutic effect. SCS improves the condition of patients with diabetic ischemic foot disease by inducing NT-3 production. Both SCS and NT-3 supplementation show therapeutic potential for ameliorating diabetic foot disease.

The Infected Diabetic Foot: Does Negative Pressure Wound Therapy with Irrigation Reduce Bioburden and Improve Wound Healing?

The aim of this study was to compare the microbial loads of patients with diabetic foot infections treated with negative pressure wound therapy (NPWT) with and without irrigation with polyhexamethylene biguanide (NPWTi-P). This is a post hoc analysis of combined data of two randomized clinical trials. We evaluated people with diabetes treated with moderate and severe diabetic foot infections that required surgery. Tissue specimens were obtained after the initial surgery and following a second planned return to the operating room after 48-72 h of NPWT or NPWTi-P, prior to the second surgery. We used quantitative polymerase chain reaction (qPCR) to determine the total microbial loads (Log10 16S copies per gram of tissue). There was no difference in mean quantitative bacterial cultures among patients that received NPWT and NPWTi-P (before first surgery Log10: NPWT = 6.4 ± 1.8, NPWTi-P = 7.5 ± 1.7 vs before second surgery Log10: NPWT = 6.7 ± 1.8, NPWTi-P = 7.6 ± 1.9 p = .12). There was no difference in wound healing (59.5% vs 50.0%, p = .51) or time to heal (127 ± 109.3 vs 143 ± 95.9), p = .71). There were fewer re-infections in people that received traditional NPWT (28.6% vs 56.3%, p = .05). Level of Clinical Evidence: Level 1.

Innovative biopolymers composite based thin film for wound healing applications

Efficient wound and burn healing is crucial for minimising complications, preventing infections, and enhancing overall well-being, necessitating the development of innovative strategies. This study aimed to formulate a novel thin film combining chitosan, carboxymethyl cellulose, tannic acid, and beeswax for improved wound healing applications. Several formulations, incorporating chitosan, carboxymethyl cellulose, tannic acid, and beeswax in various percentages, were utilized to deposit thin films via the solvent evaporation technique, Mechanical properties, morphology, antioxidant activity, antibacterial efficacy, and wound healing potential were evaluated. The optimized thin film (M4), composed of 2% chitosan, 2% carboxymethyl cellulose, and 1% tannic acid, along with 0.2% glycerol and 0.2% tween80, exhibited a thickness of 39.0 ± 1.14 μm and a tensile strength of 0.275 ± 0.003 MPa. It demonstrated a swelling degree of 283.0 ± 2.0% and a drug release capacity of 89.4% within 24 h. The film also showed a low contact angle of 40.5° and a water vapour transmission rate of 1912.25 ± 13.10 g m−2 0.24 h−1. FT-IR spectroscopy indicated that chitosan and carboxymethyl cellulose were cross-linked through amide linkages, with tannic acid occupying the interstitial spaces and hydrogen bonding stabilizing the structure. Microscopy of M4 revealed a uniform morphology. The film exhibited strong antioxidant activity of (95.17 ± 0.02%) and antibacterial efficiency (80.8%) against S. aureus. In a rabbit model, the film significantly enhanced burn and excision wound recovery, with 90.0 ± 3.3% healing for burns and 88.85 ± 1.7% for infected wounds by day 7. Complete skin regeneration was observed within 10–12 days. The M4 thin film demonstrated exceptional mechanical properties and bioactivity, offering protection against pathogens and promoting efficient wound healing. These findings suggest its potential for further investigation in treating various infections and its role in developing novel therapeutic interventions.

Umbilical cord mesenchymal stem cells combined with autologous platelet-rich plasma for lower extremity venous ulcers: A case report and literature review.

Nonhealing ulcers are difficult to manage because they deviate from the normal wound healing process. Conventional therapy cannot achieve satisfactory therapeutic effects. To verify the effectiveness of combined treatment with human umbilical cord mesenchymal stem cells (hUMSCs) and platelet-rich plasma (PRP) for nonhealing ulcers, we studied a patient with left lower limb venous ulcer (LEVU) treated with combined injection therapy. We present the case of a LEVU patient who has not healed for a long period of time (up to 1 year). LEVU was diagnosed with clinical symptoms. The hUMSCs plus PRP were injected into the wound edge and base (1 µL of cells/cm2 of wound surface), 0.5 mL at each point, with a distance of approximately 1 to 3 cm between points. The injection point was determined according to the extent of wound involvement. Seven days after hUMSC + PRP application, the wound area decreased by nearly 50%. The ulcers had almost completely healed by day 62, and no serious treatment-related toxic side effects were observed. hUMSCs can improve wound healing through re-epithelialization, increased angiogenesis, and granulation tissue formation. PRP has also been suggested to promote wound healing through the secretion of various nutritional factors. The combination of hUMSCs and PRP has a mutually reinforcing effect, which may achieve a 1 + 1 > 2 effect. Therefore, the combination of hUMSCs and PRP may be a safe and effective treatment option for LEVU.

Electrical Microneedles for Wound Treatment.

Electrical stimulation has been hotpot research and provoked extensive interest in a broad application such as wound closure, tissue injury repair, and nerve engineering. In particular, immense efforts have been dedicated to developing electrical microneedles, which demonstrate unique features in terms of controllable drug release, real-time monitoring, and therapy, thus greatly accelerating the process of wound healing. Here, a review of state-of-art research concerning electrical microneedles applied for wound treatment is presented. After a comprehensive analysis of the mechanisms of electrical stimulation on wound healing, the derived three types of electrical microneedles are clarified and summarized. Further, their applications in wound healing are highlighted. Finally, current perspectives and directions for the development of future electrical microneedles in improving wound healing are addressed.

The perioperative nursing effect of VSD closed negative pressure drainage in the treatment of emergency traumatic wound infection.

This study aims to explore the perioperative nursing effect of vacuum sealing drainage closed negative pressure drainage in the treatment of emergency traumatic wound infection. A total of 116 patients with trauma-related wound infection were admitted to the Department of orthopedics and skin wound at our hospital from April 2021 to October 2022 were selected as the study subjects. They were divided into an observation group and a control group, with 58 patients in each group. Patients in the control group received traditional wound debridement, while patients in the observation group underwent debridement with the addition of vacuum-sealed drainage closed negative pressure. The treatment outcomes, pain levels, various treatment indicators, and wound healing conditions of the 2 groups were compared. The overall effective rate of treatment in the observation group was 93.10%, which was significantly higher than the control group's rate of 75.86% (P < .05). The Visual Analog Scale scores of patients in both groups were compared at 1 hour after treatment and 6 hours after treatment (P > .05). However, at 12 hours and 24 hours after treatment, the Visual Analog Scale scores of patients in the observation group were significantly lower than those in the control group (P < .05). The observation group of patients had fewer changes of dressings after treatment compared to the control group (P < .05). The wound healing time, antibiotic usage duration, and hospitalization time were all shorter in the observation group than in the control group (P < .05). The Bates-Jensen scores of both groups of patients before treatment were compared (P > .05). After treatment, the Bates-Jensen scores in both groups decreased, and the observation group had lower scores than the control group (P < .05). The use of vacuum sealing drainage closure therapy in patients with emergency trauma-related wound infections can alleviate pain, reduce the frequency of dressing changes, accelerate wound healing, and improve wound healing outcomes. It is worthy of clinical promotion.

Characterizing Fibroblast Heterogeneity in Diabetic Wounds Through Single-Cell RNA-Sequencing.

Diabetes mellitus is an increasingly prevalent chronic metabolic disorder characterized by physiologic hyperglycemia that, when left uncontrolled, can lead to significant complications in multiple organs. Diabetic wounds are common in the general population, yet the underlying mechanism of impaired healing in such wounds remains unclear. Single-cell RNA-sequencing (scRNAseq) has recently emerged as a tool to study the gene expression of heterogeneous cell populations in skin wounds. Herein, we review the history of scRNAseq and its application to the study of diabetic wound healing, focusing on how innovations in single-cell sequencing have transformed strategies for fibroblast analysis. We summarize recent research on the role of fibroblasts in diabetic wound healing and describe the functional and cellular heterogeneity of skin fibroblasts. Moreover, we highlight future opportunities in diabetic wound fibroblast research, with a focus on characterizing distinct fibroblast subpopulations and their lineages. Leveraging single-cell technologies to explore fibroblast heterogeneity and the complex biology of diabetic wounds may reveal new therapeutic targets for improving wound healing and ultimately alleviate the clinical burden of chronic wounds.

Topical Reconstituted High-Density Lipoproteins Elicit Anti-Inflammatory Effects in Diabetic Wounds.

Objective: Reconstituted high-density lipoproteins (rHDL) improve wound healing in diabetes. We aimed to determine if rHDL elicit anti-inflammatory effects in diabetic wounds, as a mechanism to explain their wound healing benefits. Approach: Diabetes was induced using streptozotocin in C57Bl6/J mice. Two full-thickness wounds were placed on the subflanks of diabetic and nondiabetic (ND) mice. Phosphate-buffered saline (PBS) or rHDL (50 µg/wound/day) were applied topically. Wound closure was assessed daily. Inflammatory gene transcripts were measured by qPCR and proteins by Western blotting and enzyme-linked immunosorbent assay in wounds collected at baseline, 24 h, and 3 days postwounding. Wound macrophages were assessed by flow cytometry 7 days postwounding. The fate of fluorescent 3,3-dioctadecyloxacarbocyanine, perchlorate (DiO)-labeled rHDL was tracked by flow cytometry, fluorescent imaging, and microscopy. Results: In diabetic mice, rHDL increased wound closure rates at days 6 (+288%, p < 0.01) and 7 (+639%, p < 0.0001) postwounding, compared with PBS controls. After 3 days, rHDL-treated diabetic wounds had lower Rela (-65%) and C-C motif chemokine ligand 2 (Ccl2) (-59%) mRNA levels and CCL2 protein (29%) than PBS controls, p < 0.05 for all. Wound macrophage content was higher in diabetic than ND wounds, but rHDL did not change macrophage content or polarity. DiO-rHDL were taken up by key wound cells including fibroblasts, macrophages, keratinocytes and endothelial cells, and retained in wounds for at least 48 h. Innovation: rHDL exerts anti-inflammatory effects in diabetic wounds early postwounding, which may contribute to its wound healing properties. Conclusion: The anti-inflammatory properties of rHDL in diabetic wounds present topical rHDL as a novel treatment option for improving healing in patients with diabetic foot ulcers.

HES1 revitalizes the functionality of aged adipose-derived stem cells by inhibiting the transcription of STAT1.

The effectiveness of adipose-derived stem cells (ADSCs) in therapy diminishes with age. It has been reported that transcription factors (TFs) play a crucial role in the aging and functionality of stem cells. Nevertheless, there is limited understanding regarding the involvement of TFs in the aging mechanism of ADSCs. RNA sequencing (RNA-seq) was utilized to discern the differentially expressed genes in ADSCs obtained from donors of varying ages. TFs exhibiting significant variations across age groups were identified and subsequently validated. ADSCs were manipulated to exhibit either enhanced expression or reduced levels of HES1 and STAT1 via lentivirus transfection and small interfering RNA (siRNA) techniques. The impact of these genetic alterations on ADSCs' proliferation, migration, and cellular senescence was assessed using EdU, transwell, and senescence-activated β-galactosidase (SA-β-gal) staining assays. The DNA sequences bound by HES1 were investigated through the CUT & Tag assay. Lastly, the therapeutic efficacy of aged ADSCs with HES1 overexpression was evaluated in skin injury model of male Sprague-Dawley rats. 678 genes showed differential expression between ADSCs obtained from young and old donors (Y-ADSCs and O-ADSCs), with 47 of these genes being TFs. Notably, the expression of the TF hairy and enhancer of split 1 (HES1) was notably reduced in ADSCs from old donors. Introducing HES1 overexpression in aged ADSCs resulted in improved cellular function and the suppression of cellular senescence, while reducing HES1 levels in young ADSCs had the opposite effect. Mechanistically, HES1 was found to interact with the promoter region of another TF, signal transducer and activator of transcription 1 (STAT1), to inhibit its transcription. Knocking down STAT1 could fully reverse the negative effects caused by decreased HES1 in ADSCs, leading to a reduction in the secretion of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-8. Ultimately, restoring HES1 expression in aged ADSCs demonstrated enhanced therapeutic potential in promoting skin wound healing. HES1 acts as an inhibitor of cellular senescence in the aging progression of ADSCs through the modulation of STAT1 expression, suggesting a promising avenue for rejuvenating senescent ADSCs and improving wound healing.

A novel solvent-extruded tacrolimus-eluting suture for attenuated inflammation and scarring in skin repair

This study aimed to design an absorbable suture that locally delivers the immunosuppressive agent, tacrolimus (FK506), to attenuate scar tissue formation by modulating inflammation. As the suture degrades, it releases FK506 directly into the repair site. The poly (l-lactide-co-caprolactone) (PLLA-PCL) polymer and 0.2 % wt FK506 were co-extruded using a solvent extrusion technique to generate the drug-eluting sutures. The properties of the generated sutures were assessed regarding FK506 release in vitro, wound closure in an in vivo murine model, murine skin histology for structural and inflammatory markers, and mechanical strength of both sutures and healed murine skin. The generated suture consistently released FK506 at ≤10 ng/day rates. Following annealing, the sutures retained 60 % of their anticipated tensile strength, exhibiting enhanced ductility. The histological examination and in vivo murine study indicated that wounds treated with FK506-eluting PLLA-PCL sutures produced a thinner epidermal layer, enhanced integrin β4 expression, increased keratinocyte presence, attenuated inflammation, and reduced scarring, demonstrating healed tissue improvements compared with those treated with the placebo, poly (glycolic-co-caprolactone) (PGCL), sutures. Mechanical evaluations of healed tissue indicated that drug-PLLA-PCL sutures did not reduce the mechanical strength of the skin compared to placebo PGCL sutures. The FK506-eluting PLLA-PCL sutures show promising results in advancing wound healing by offering targeted drug delivery. This innovative method can improve wound healing and provide a streamlined approach to scar management. Continued research, optimization, and broad-scale studies are needed to refine the manufacturing process and ensure that the properties of the suture meet clinical requirements.

Biodegradable Oxygen‐Generating Microneedle Patches for Regenerative Medicine Applications

Upon injury, regenerating skin is metabolically active and requires oxygen for physiological processes related to wound healing. Such processes can be halted in hypoxic conditions common in chronic wounds. Microneedle arrays (MNAs) have been demonstrated to improve therapeutic delivery and wound healing. Recently, few studies have explored the use of oxygen‐releasing MNAs; however, they involve complex manufacturing and handling and fail to eliminate cytotoxic byproducts. To address these challenges, biodegradable and mechanically robust gelatin methacryloyl‐based MNAs are developed that can penetrate the tissue and release oxygen upon exposure to interstitial fluid and wound exudates. The oxygen release rate and biocompatibility of the developed MNAs with different compositions are evaluated and optimized. Interestingly, in vitro studies demonstrate that the optimized compositions can release oxygen at therapeutic levels and significantly increase viability of chronically hypoxic cells to match that of normoxic cells. In vivo studies further confirm that the optimized oxygen‐generating MNAs do not cause any harm or impair healing in a murine model of acute skin injury. Additionally, transcriptomic analysis reveals upregulation of key pathways related to fibroblast motility, lipid metabolism, and a marked reduction in inflammatory signaling, all of which contribute to improved wound healing. The developed strategy can introduce new opportunities in elimination of hypoxia and therefore treatment of chronic wounds.