Search Results (177)

Repairing and regenerating tissue barriers is a key challenge in regenerative medicine. Stem cells play a crucial role in restoring the structural and functional integrity of key epithelial barrier surfaces, including the skin and mucosa. This review analyzes the role of dental pulp stem cells (DPSCs) and their derivatives, including extracellular vesicles, conditioned medium, and intracellular factors, in accelerating skin wound healing. The key mechanisms include: (1) DPSCs regulating inflammatory microenvironments by promoting anti-inflammatory M2 macrophage polarization; (2) DPSCs activating vascular endothelial growth factor (VEGF) to drive angiogenesis; (3) DPSCs optimizing extracellular matrix (ECM) spatial structure through matrix metalloproteinase/tissue inhibitor of metalloproteinase (MMP/TIMP) balance; and (4) DPSCs enhancing transforming growth factor-β (TGF-β) secretion to accelerate granulation tissue formation. Collectively, these processes promote wound healing. In addition, we explored potential factors that accelerate wound healing in DPSCs, such as oxidative stress, mechanical stimulation, hypertension, electrical stimulation, and organoid modeling. In addition to demonstrating the great potential of DPSCs for skin repair, this review explores their translational prospects in mucosal regenerative medicine. It covers the oral cavity, esophagus, colon, and fallopian tube. Some studies have found that combining DPSCs and their derivatives with drugs can significantly enhance their biological effects. By integrating insights from skin and mucosal models, this review offers novel ideas and strategies for treating chronic wounds, inflammatory bowel disease, and mucosal injuries. It also lays the foundation for connecting basic research results with clinical practice. This represents a significant step forward in tackling these complex medical challenges and lays a solid scientific foundation for developing more targeted and efficient regenerative therapies. Full article

Wound healing is a complex biological process that benefits from advanced biomaterials capable of modulating inflammation and promoting tissue regeneration. In this study, cerium oxide nanoparticles (CeO₂NPs) were green-synthesized using Hemerocallis citrina extract, which served as both a reducing and stabilizing agent. The CeO₂NPs exhibited a spherical morphology, a face-centered cubic crystalline structure, and an average size of 9.39 nm, as confirmed by UV-Vis spectroscopy, FTIR, XRD, and TEM analyses. These nanoparticles demonstrated no cytotoxicity and promoted fibroblast migration, while significantly suppressing the production of inflammatory mediators (TNF-α, IL-6, iNOS, NO, and ROS) in LPS-stimulated RAW264.7 macrophages. Gene expression analysis indicated M2 macrophage polarization, with upregulation of Arg-1, IL-10, IL-4, and TGF-β. Aligned polycaprolactone/polylactic acid (PCL/PLA) nanofibers embedded with CeO₂NPs were fabricated using electrospinning. The composite nanofibers exhibited desirable physicochemical properties, including porosity, mechanical strength, swelling behavior, and sustained cerium ions release. In a rat full-thickness wound model, the CeO₂ nanofiber-treated group showed a 22% enhancement in wound closure compared to the control on day 11. Histological evaluation revealed reduced inflammation, enhanced granulation tissue, neovascularization, and increased collagen deposition. These results highlight the therapeutic potential of CeO₂-incorporated nanofiber scaffolds for accelerated wound repair and inflammation modulation. Full article

Wound infections remain significant challenges for current tissue adhesives, primarily due to their poor adhesion in moist environments, slow bonding, cytotoxicity, and limited antibacterial properties. Slightly acidic electrolyzed water (SAEW), a potent disinfectant, suffers from limited stability due to chlorine loss. This study developed a novel SAEW-based hydrogel (SAEW-gel) by combining SAEW with chitosan and β-glycerol disodium phosphate to improve its stability and therapeutic potential. SAEW-gel demonstrated high water absorption, long-term water retention, and enhanced antibacterial activity against S. aureus and E. coli compared to SAEW alone. It maintained germicidal efficacy after prolonged storage and significantly accelerated wound healing in a rat model, achieving a 95.41% healing rate by the 12th day of treatment. Mechanistically, SAEW-gel reduced inflammatory cell infiltration, promoted granulation and collagen formation, and regulated inflammatory markers (IL-6, IL-1β, TNF-α, MPO, HYP). These findings highlight SAEW-gel as a promising biomaterial for treating infectious wounds and support its potential for future clinical application. Full article

Wound healing remains a significant clinical challenge worldwide, and effective management strategies are essential for improving outcomes. This study evaluated SCderm Matrix, a novel acellular dermal matrix (ADM) patch developed using supercritical carbon dioxide (sCO₂) processing of human skin tissue. This innovative processing method preserves structural integrity while enhancing biocompatibility, resulting in a patch characterized by porous architecture, uniform thickness, excellent tensile strength, and optical transparency. In vivo wound healing experiments using full-thickness skin wounds in Sprague–Dawley rats demonstrated the patch’s superior performance. Treatment with the sCO₂ ADM patch accelerated wound closure, reduced inflammation, and enhanced granulation tissue formation compared to both untreated controls and two commercially available ADM products. Histological analysis revealed improved re-epithelialization and collagen deposition, while molecular and immunohistochemical assessments showed decreased reactive oxygen species (ROS) and pro-inflammatory cytokines. Simultaneously, the treatment upregulated key proliferation and remodeling markers including alpha smooth muscle actin (α-SMA), vimentin, and transforming growth factor beta 1 (TGF-β1). These findings demonstrate that the SCderm Matrix promotes wound healing through multiple mechanisms: modulating inflammatory responses, enhancing antioxidant defenses, and supporting tissue regeneration. The results suggest this biomaterial has significant potential as an effective and versatile solution for clinical wound care applications. Full article

Background/Objectives: Foam dressings are designed for their ability to manage exudate and are selected to optimize wound repair. Various foam dressings are available, ranging from basic polyurethane to more sophisticated options, incorporating active components to combat infections or foster healing. This study investigates the requirements for the most suitable foam dressing through a combination of field research, laboratory testing, and clinical evaluation. Methods: We tested 17 foam dressings commonly used by wound care professionals while attending an international conference. An effective foam dressing should absorb wound fluid for several days, as wound care professionals value absorption and retention capacity, often favoring less frequent changing dressings, preferably twice a week or even weekly. Results: The foam dressings tested can absorb the expected amount of exudate typically produced by different wound types. There is some variability in retention capacity and product prices, resulting in differences in cost-effectiveness among products. In addition, some dressings are enriched with active ingredients that can accelerate healing through their antimicrobial and anti-inflammatory properties, such as foam dressings infused with silver or honey. A honey-based foam dressing was evaluated in a clinical survey involving eight wound care specialists, and four clinical cases with varying wound pathologies were discussed in more detail to highlight its key properties. Conclusions: Ideally, a foam dressing should have adequate absorption and retention capacities, effectively resolve and prevent infections, protect against external trauma, ensure optimal patient comfort without damaging newly formed granulation tissue, accelerate wound healing processes, and reduce wound care time (e.g., remaining in place for 7 days). Together, these factors make honey- or silver-loaded foam dressings more cost-effective than plain dressings due to their antimicrobial activities and ability to nourish tissues. Full article

The aim of this study was to achieve the high secretion and expression of thymosin β4 derived from Pinctada fucata in Pichia pastoris, as well as to investigate its antibacterial properties and biological effects in promoting wound healing. The recombinant thymosin β4 protein (rTβ4) exhibited no hemolytic activity on rabbit red blood cells and demonstrated significant antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), with a minimum inhibitory concentration (MIC) of 25 μg/mL. It effectively inhibited bacterial growth and disrupted the cell wall and membrane structure of the bacteria. In the Sprague Dawley (SD) rat wound healing model, the wound healing rate in the rTβ4 treatment groups (at concentrations of 12.5 and 25 μg/mL) was significantly higher than that in the control group (p < 0.05), and the healing effect was comparable to that of the positive control group (Kangfu Xin solution, KFX). The histopathological study demonstrated that rTβ4 could reduce the infiltration of inflammatory cells and promote the proliferation and re-epithelialization of granulation tissue. In conclusion, this study successfully achieved the high expression of thymosin β4 derived from Pinctada fucata in Pichia pastoris and validated its antibacterial and wound healing potential through both In vitro and In vivo experiments. Full article

Background: Diabetic foot ulcers (DFUs) remain a major complication of diabetes, characterized by impaired wound healing, high infection risk, and an increased likelihood of limb amputation. Platelet-rich plasma (PRP) has emerged as a promising adjunctive therapy due to its regenerative properties, promoting angiogenesis, modulating inflammation, and accelerating tissue repair. Methods: This literature review explores the current evidence regarding the use of PRP in the management of DFUs. It was conducted using the PubMed database to evaluate the efficacy of PRP in DFUs. The search was restricted to studies published in the last 10 years, including randomized controlled trials, meta-analyses, and systematic reviews. The inclusion criteria focused on studies assessing PRP as a standalone treatment or in combination with other wound care strategies, evaluating key clinical outcomes such as wound healing rates, infection control, tissue regeneration, and amputation prevention. Results: A total of 35 studies met the inclusion criteria, including 11 meta-analyses, 15 review articles, and 9 clinical trials. PRP demonstrated potential benefits in accelerating wound healing, reducing inflammation, and promoting granulation tissue formation. Additionally, PRP combined with negative-pressure wound therapy (NPWT) showed superior outcomes in reducing amputation rates. However, findings varied based on patient characteristics, PRP preparation techniques, and treatment protocols. Conclusions: PRP represents a valuable adjunct in DFU management, contributing to improved healing outcomes and reduced complications. However, the lack of standardized protocols and variability in clinical results highlight the need for further large-scale, multicenter studies to establish its definitive role in diabetic wound care. Full article

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe genetic disease caused by COL7A1 mutations. It leads to skin fragility, chronic inflammation, and impaired wound healing. The condition often results in fibrotic scarring, pseudosyndactyly, and cutaneous squamous cell carcinoma (SCC). However, current animal models fail to fully replicate chronic RDEB wounds. In this study, we used Collagen VII-hypomorphic mice (Col7a1^flNeo/flNeo) and created full-thickness wounds on their paw skin, an area prone to fibrosis due to mechanical stress. We analyzed the healing process using histology, immunofluorescence, and electron microscopy. The RDEB mice showed delayed wound closure, increased inflammation, and poor granulation tissue formation. At 30 days post-injury, we observed persistent fibrosis, with elevated levels of Collagen I, α-SMA+ myofibroblasts, and tenascin-C. These mice also had fewer intraepidermal nerve fibers, which may help explain the neuropathic pain associated with RDEB. Our model reproduces the main features of chronic RDEB wounds. It offers a useful tool for evaluating therapies aimed at reducing inflammation, fibrosis, and tumor risk in these patients. Full article

The cicatrization process, which is critical to equine health, directly affects overall well-being by preventing infection, minimizing tissue damage, and restoring optimal function. Herein, we present a case of a 5-year-old sorrel mare with a torn skin wound on the dorsal aspect of the metatarsal region of the left hind limb, treated locally with an antibiotic-free transparent hydrogel-based patch while monitoring its healing process. The patch induced pink granulation tissue in the treated area after 42 days, while keloid formation was observed in the untreated area. Wound measurements showed a reduction over time with patch treatment, with complete healing achieved at 116 days. Capillary formation and a velvety appearance were observed on day 80. Histological analysis revealed mature granulation tissue, fibrocyte formation, abundant capillaries, organized collagen fibrils, and development of type III collagen in the treated area. Interestingly, no inflammatory response was observed during treatment. The hydrogel patch not only accelerated healing, but also controlled excessive granulation tissue formation. This treatment represents an innovative approach to equine wound management that updates applications for owners while reducing costs. Full article

Background: Chronic diabetic foot ulcers are a global health challenge, affecting approximately 18.6 million individuals each year. The timely and accurate prediction of wound healing paths is crucial for improving treatment outcomes and reducing complications. Methods: In this study, we apply predictive modeling to the case study of diabetic foot ulcers, analyzing and comparing multiple models based on Deep Neural Networks (DNNs) and Machine Learning (ML) algorithms to enhance wound prognosis and clinical decision making. Our approach leverages a dataset of 1766 diabetic foot wounds, each monitored for at least three visits, incorporating key clinical wound features such as WBP scores, wound area, depth, and tissue status. Results: Among the 12 models evaluated, the highest accuracy (80%) was achieved using a three-layer LSTM recurrent DNN trained on wound instances with four visits. The model performance was assessed through AUC (0.85), recall (0.80), precision (0.79), and F1-score (0.80). Our findings indicate that the wound depth and area at the first visit followed by the wound area and granulated tissue percentage at the second visit are the most influential factors in predicting the wound status. Conclusions: As future developments, we started building a weakly supervised semantic segmentation model that classifies wound tissues into necrosis, slough, and granulation, using tissue color proportions to further improve model performance. This research underscores the potential of predictive modeling in chronic wound management, specifically in the case of diabetic foot ulcers, offering a tool that can be seamlessly integrated into routine clinical practice. Full article

Background/Objectives: The insertion of engineered scaffolds and tissues requires precise surgical implantation with minimal interfacial scarring. Nanometric scale material polishing technologies developed for manufacturing microelectronic circuits make it possible to polish and sharpen surgical instruments at near-atomic-scale precision. We tested the hypothesis that the use of precision-sharpened scalpel blades would result in less tissue inflammation and incisional scarring. Methods: Parallel contralateral para-spinal longitudinal 4 cm long skin incisions in guinea pigs were performed, one side with a standard scalpel blade (SB) and the other with a polished nanometric scale, engineered experimental scalpel blade (EB). The side used for the polished blade was alternated and blinded from the histochemistry analysis team. The wound was excised at five time points (1, 3, 7, 16, and 60 days) with five animals per group. Histological and histochemical differences were compared. Results: The EB resulted in less bleeding, better wound adherence, relatively less macrophage density, scar volume, and granulation tissue, and significantly reduced levels of M1, M2, and TGF-β expression. Conclusions: Nanometric-scale-polished surgical scalpel blades produce significantly less tissue inflammation, scarring, and fibrosis. Full article

Diabetic foot ulcers (DFUs) are a devastating complication of diabetes, presenting limited treatment success rates due to their complex pathophysiology. Bone morphogenetic protein 7 (BMP7) confers tissue protective and regenerative functions, but its potential role in diabetic wound healing is unknown. The aim of this study was to investigate the effects of topical BMP7 treatment in wound healing using a streptozotocin-induced diabetic mouse model. The expression of markers of wound healing progression were detected using RT-PCR or immunohistochemistry. Overall, BMP7 improved wound closure, as well as maturation of granulation tissue and collagen deposition, as evidenced by hematoxylin and eosin and Masson’s trichrome histological analysis. The expression of inflammatory markers (IL-6, TNF-α) and matrix metalloproteinase-9 were decreased in BMP7-treated wounds, together with the number of pro-inflammatory M1 macrophages and T lymphocytes. The number of anti-inflammatory M2 macrophages was increased in BMP7-treated wounds. Moreover, BMP7 decreased oxidative stress and increased Ki67⁺ cells and CD31⁺ cells, indicating induced proliferation and angiogenesis in the wound bed compared to the control wounds. Finally, BMP7 activated the ERK pathway and suppressed the p38 pathway in diabetic wounds. Together, our data suggest that BMP7 enhanced skin wound healing in diabetes by decreasing local inflammation and oxidative stress, which promoted a regenerative environment for collagen deposition, wound maturation, cell proliferation, and angiogenesis. These findings underline BMP7 as a potential therapeutic agent for the treatment of skin wounds in diabetes. Full article

Background/Objectives: Chronic wounds represent a growing challenge for the aging population, significantly impairing their quality of life, increasing the frequency of medical consultations, and imposing substantial healthcare costs. Chronic wounds are prone to complications, including local and systemic infections, and in severe cases, amputations. The therapeutic use of live larvae from the blowfly Lucilia sericata (biological debridement) has regained attention for its ability to debride necrotic tissue and stimulate granulation. Despite its benefits, this therapy is constrained by the logistical challenges of producing and delivering live larvae and by patient adherence issues. Objectives: This study aimed to develop a lyophilized extract of Lucilia sericata larvae and evaluate its efficacy in treating chronic wounds. Methods: A lyophilized maggot extract (Larveel^®, Alpha-Biocare GmbH, Neuss, Germany) of the larvae of Lucilia sericata was produced under GMP conditions. In a total of ten patients with chronic refractory wounds, the extract was used in individual therapeutic trials and its effect on bacterial colonization and wound healing was investigated. Wound healing was documented photographically and measured visually in terms of a reduction in the wound slough, an increase in the granulation tissue, and a reduction in the wound area. Results: Of the ten patients, three discontinued their treatment due to P. aeruginosa colonization. In seven patients, significant fibrin reduction, granulation, and wound healing occurred, with two achieving complete closure and four showing advanced epithelialization. Conclusions: In 7 of the 10 patients, the application of the extract led to a marked reduction in wound slough, and improved granulation and the progression of wound healing. These effects are likely attributable to the extract’s ability to disrupt bacterial biofilm formation. The findings suggest that this novel therapeutic approach may provide a practical and effective alternative to live larval therapy for managing chronic wounds. Full article

Background/Objectives. Chronic wounds pose a substantial global healthcare burden exacerbated by aging populations and the increasing prevalence of conditions such as diabetes, peripheral vascular disease, and venous insufficiency. Impaired physiological repair mechanisms, including angiogenesis, collagen synthesis, and re-epithelialization, hinder the healing process in chronic wounds. Many of these physiological processes are dependent on their interaction with copper. We hypothesized that the targeted delivery of copper ions to the wound bed would enhance healing. Methods. Wound dressings impregnated with copper oxide microparticles were designed to ensure the controlled release of copper ions. The efficacy of these dressings was evaluated using non-infected wound models, including diabetic mouse models compared against control and silver dressings. Outcome measures included wound closure rates, epidermal skin quality assessed by histopathological examination, and gene expression profiling. Clinical applications were assessed through diverse case studies and controlled trials involving chronic wound management. Results. Copper dressings significantly accelerated wound closure and enhanced angiogenesis compared to control and silver dressings. Histopathological analyses revealed faster granulation tissue formation, epidermal regeneration, and neovascularization. Gene expression studies showed upregulation of critical angiogenic factors such as VEGF and HIF-1α. Investigations and clinical observations corroborated improved healing across various chronic wound types, including non-infected wounds. Conclusions. Copper is essential for wound healing, and copper-impregnated dressings provide a promising solution for chronic wound management. By enhancing angiogenesis and tissue regeneration, these dressings go beyond antimicrobial action, offering a cost-effective and innovative alternative to conventional therapies. Copper dressings represent a transformative advancement in addressing the challenges of chronic wound care. Full article

PDRN, polydeoxyribonucleotide, which is used as a tissue-regeneration material, is present in human cells under physiological conditions and stimulates regeneration and metabolic activity. PDRN can be used as a biomaterial for several types of regeneration, including wound healing, to promote cell growth and growth-factor production. The aims of this study were to determine the effect of PDRN derived from human placenta-derived mesenchymal stem cells (hPD-MSCs) on cellular regeneration through A2A receptor signaling and to investigate its therapeutic effects in a mouse model of wound healing. Human PDRN (UNIPlax) was extracted from hPD-MSCs fragmented via a sonication system and evaluated for its effect on the migration of HaCaT cells in an in vitro system and in a wound-healing mouse model in vivo. Compared with the sham treatment, UNIPlax treatment significantly increased the migration of injured HaCaT cells (p < 0.05). Additionally, the tube formation of human umbilical vein endothelial cells (HUVECs) was greater than that of the sham group (p < 0.05), and the effects of this treatment were mediated through the A2A receptor. Furthermore, UNIPlax treatment led to a decrease in wound size; in addition, the area of granulation and the rate of collagen formation at the wound site were significantly greater than those in the sham group in the wound-healing mouse model (p < 0.001). We also confirmed that UNIPlax promoted tissue regeneration and the expression of VEGF through the A2A receptor. Taken together, these findings indicate that UNIPlax has potential for regeneration of damaged tissues, including during wound healing. Full article