Wound Closure Research Articles (Page 1)

In the field of regenerative therapy, the stromal vascular fraction (SVF) extracted from adipose tissue has been widely recognized for its significant benefits. However, the cellular composition and therapeutic effect of SVF products prepared via different methods are unclear. SVF cells were obtained via three approaches: (1) generation of the SVF via mechanical emulsification (M-SVF), (2) generation of the SVF via laboratory enzymatic digestion (L-SVF), and (3) generation of the SVF via commercial cell separation systems (C-SVF). We evaluated their healing effects on mouse wounds. Additionally, we utilized single-nucleus RNA sequencing (snRNA-seq) technology to explore the cellular composition of the C-SVF. The cell yield of C-SVF was comparable to that of L-SVF. During in vitro culture, C-SVF exhibited enhanced proliferation and a reduced proportion of apoptotic cells. In a mouse wound model, the application of C-SVF facilitated the closure of mouse wounds and improved collagen remodeling and angiogenesis in the wound area. Additional snRNA-seq analysis revealed that APOE + adipose-derived stem cells and immune cells, especially M2 anti-inflammatory macrophages, are enriched in C-SVF, which together promote wound repair, and that APOE + adipose-derived stem cells (ADSCs) and immune cells, especially M2 anti-inflammatory macrophages, are enriched in C-SVF, which jointly regulate and promote wound repair. A commercial extraction system is an effective method for isolating viable SVF cells enriched with APOE + ADSCs and M2 macrophages.

Amniotic membrane extract (AME) is widely recognized for its anti-inflammatory, antifibrotic, and antiangiogenic properties, making it a valuable option for corneal wound healing. However, short retention time and rapid degradation of AME limit its clinical efficacy. In this study, we developed a novel AME-SupraGel that combines the therapeutic benefits of AME with the sustained-release capabilities of a supramolecular peptide-based hydrogel. The design of AME-SupraGel addresses the limitations of the AME solution by enhancing retention on the ocular surface and providing prolonged therapeutic action. In vitro scratch-wound assays demonstrated significantly faster wound closure in corneal epithelial cells treated with AME-SupraGel than in those treated with AME or the peptide hydrogel alone. Moreover, AME-SupraGel exhibited superior biocompatibility, as evidenced by CCK-8 assays, and achieved sustained release of hepatocyte growth factor over 54 h. In an alkali burn-induced corneal injury model, AME-SupraGel significantly reduced corneal opacity and neovascularization, promoted clearer corneal surfaces, and limited blood vessel formation compared to other treatments. Additionally, the stability of the active components of AME-SupraGel at different temperatures enhances its clinical convenience by facilitating long-term storage without compromising efficacy. Overall, AME-SupraGel represents a promising therapeutic strategy for corneal wound healing, offering a noninvasive, long-lasting, and effective treatment option for ocular surface injuries.

Abdominoplasty is a widely performed cosmetic procedure aimed at improving abdominal contour and function. Seroma formation, with an incidence of approximately 10.9%, remains a common and challenging complication. Traditional preventive measures like suction drains and progressive tension sutures (PTS) are effective but can increase operative time and patient discomfort. To address these limitations, the Absorbable Running Barbed Arch Suture (ARBAS) technique was introduced, aiming to simplify wound closure while preventing fluid accumulation. To evaluate the safety and effectiveness of the ARBAS technique in preventing seroma formation and its impact on operative time and recovery. A retrospective observational study was conducted on 74 patients who underwent abdominoplasty with or without rectus diastasis repair between April 2021 and May 2023. All surgeries were performed by a single senior surgeon using the ARBAS technique. The primary endpoint was seroma incidence; secondary endpoints included drainage volume, duration of drainage, and total operative time. No postoperative seromas were observed. Average drainage volume decreased from 36ml on day one to 19ml on day two, allowing early drain removal within 48hours for most patients. The ARBAS technique added only 8minutes to the operative time-significantly less than PTS. No major complications, such as infection, hematoma, or flap necrosis, were reported. The ARBAS technique is a safe and efficient method for seroma prevention in abdominoplasty. It shortens operative time compared to traditional methods, supports faster recovery, and enhances patient comfort. Further multicenter studies are recommended to validate these results and promote its widespread adoption. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Severe hemorrhage and wound inflammation are major risk factors contributing to high mortality after tissue trauma. Therefore, there is an urgent need to develop emergency materials that can rapidly and effectively close wounds while simultaneously controlling bleeding and infection. Although current clinical bioadhesives can fill surgical voids and support tissue repair, they generally lack sufficient adhesive strength and anti-inflammatory properties, which limit their effectiveness in inflammatory wound environments. In this study, a kind of bioadhesive hydrogel was developed using a simple heating and mixing strategy with natural building blocks, including polysaccharides, lipoic acid, and natural polyphenol extracts. Through multiple non-covalent interactions (such as hydrogen bonding and electrostatic interactions), the resulting bioadhesive hydrogels exhibited excellent tissue adhesion and hemostatic properties. Moreover, these hydrogels also demonstrated outstanding anti-inflammatory effects, biocompatibility, and favorable biodegradability, effectively promoting both linear and burn wound healing. This work presents a novel strategy for achieving strong bioadhesion using natural molecules and provides a promising approach for the development of multifunctional wound dressings designed to support tissue regeneration.

Skin aging is associated with fibroblast senescence, impaired wound healing, and dysregulation of markers such as sirtuin 1 (SIRT1) and fibroblast activation protein-α (FAP-α). It is known that proliferation and migration decrease in aging fibroblasts, which delays the repair process. Metformin, a widely used anti-diabetic drug, can regulate cellular senescence pathways. This study evaluated the effects of metformin on wound healing and SIRT1 and FAP-α expression in senescent fibroblasts. Cellular senescence was induced in primary human dermal fibroblasts using 100µM hydrogen peroxide (H2O2), as validated by a WST-8 assay and SA-β-gal staining. Wound healing assay and immunocytochemistry were performed on control, senescent, and metformin-treated groups (2.5, 5, and 10mM). Wound closure was significantly impaired in senescent fibroblasts (38% at 72h versus 89% in the control group). Metformin restored wound healing in a dose-dependent manner; the 10mM group achieved 94% closure at 72h, which was comparable to the control group. SIRT1 expression decreased in senescent fibroblasts (90.17 ± 4.67 vs. 124.83 ± 4.31 in controls, p < 0.001) and increased progressively with metformin treatment, reaching control levels at 10mM. FAP-α expression increased in senescent fibroblasts (91.83 ± 4.36 vs. 78.17 ± 2.56 in controls, p < 0.05) and declined towards baseline with metformin treatment, being significantly reduced at 5 and 10mM. Metformin improved wound healing capacity and normalized age-related alterations in SIRT1 and FAP-α expression in senescent fibroblasts. These results imply that metformin alleviates senescence-associated dysfunction, suggesting its potential as a therapeutic agent to enhance wound repair in aging skin.

Platelet-rich plasma (PRP) is an autologous blood-derived concentrate increasingly utilized in regenerative medicine for its ability to accelerate healing and tissue repair. PRP is broadly classified by leukocyte content, fibrin architecture, and platelet concentration, with classification systems developed to standardize characterization. Preparation methods, including single- or double-spin centrifugation and buffy coat techniques, influence the final composition of PRP, determining the relative proportions of platelets, leukocytes, plasma proteins, and extracellular vesicles. These components act synergistically, with platelets releasing growth factors (e.g., VEGF, PDGF, TGF-β) that stimulate angiogenesis and matrix synthesis, leukocytes providing immunomodulation, plasma proteins facilitating scaffolding, and exosomes regulating intercellular signaling. Mechanistically, PRP enhances tissue repair through four key pathways: platelet adhesion molecules promote hemostasis and cell recruitment; immunomodulation reduces pro-inflammatory cytokines and favors M2 macrophage polarization; angiogenesis supports vascular remodeling and nutrient delivery; and serotonin-mediated pathways contribute to analgesia. These processes establish a regenerative microenvironment that supports both structural repair and functional recovery. Clinically, PRP has been applied across multiple specialties. In orthopedics, it promotes tendon, cartilage, and bone healing in conditions such as tendinopathy and osteoarthritis. In dermatology, PRP enhances skin rejuvenation, scar remodeling, and hair restoration. Gynecology has adopted PRP for ovarian rejuvenation, endometrial repair, and vulvovaginal atrophy. In dentistry and oral surgery, PRP accelerates wound closure and osseointegration, while chronic wound care benefits from its angiogenic and anti-inflammatory effects. PRP has also favored gingival recession coverage, regeneration of intrabony periodontal defects, and sinus grafting. Although preparation heterogeneity remains a challenge, PRP offers a versatile, biologically active therapy with expanding clinical utility.

This preclinical study evaluated the influence of two defect morphologies on graft material displacement (GMD) during primary wound closure in horizontal bone augmentation (HBA). Secondary aims included assessing the effect of membrane stabilization and the role of local soft tissue characteristics on GMD. Standardized HBA procedures following guided bone regeneration principles were performed on fresh pig hemimandibles. Each mandible received two sequential HBAs, randomized for defect morphology-partially contained (PCD) vs. contained (CD)-and membrane stabilization with (+Pins) or without (-Pins) four fixation pins. GMD was assessed using cone-beam computed tomography and intraoral scanning by comparing graft dimensions before and after wound closure, at ninelevels from the implant platform and across nine delimited sections, respectively. Sixty HBA procedures were analyzed. A notable GMD was observed for both PCD and CD, with no significant differences between them. In contrast, membrane stabilization significantly reduced three-dimensional GMD across all sections, with the most pronounced effect in the central-crestal section (p < 0.001). At the implant platform level, GMD was -15.8% ± 25.6% with pins vs. -38.1% ± 27.4% without pins (p < 0.001). Across all groups, GMD occurred in an apico-lateral direction, with the greatest volume loss in the central-crestal, mesial, and distal crestal sections. Soft tissue phenotype did not affect GMD (p ≥ 0.240). Defect morphology did not significantly influence the notable apico-lateral GMD. However, membrane stabilization using pins effectively reduced graft displacement, minimizing movement during primary wound closure.

The fibula free flap (FFF) is a mainstay in maxillofacial reconstruction, yet donor site morbidity remains a significant clinical concern. Closure technique is a key factor influencing complication rates, but comparative data remain heterogeneous. This study provides a technique-dependent analysis of 60-day donor site wound healing in FFF with skin paddles and reports a two-stage closure approach. A retrospective review of 211 patients undergoing FFF between 2017 and 2024 was conducted. Donor site complications within the first 60 postoperative days were assessed and stratified by closure technique: one-stage split-thickness skin grafting (STSG) with or without negative pressure wound therapy (NPWT), and a two-stage closure consisting of one-week NPWT followed by STSG. Multivariate logistic regression was applied to identify independent predictors for complications. Overall, 50.2% of patients experienced donor site complications, with wound healing disorders (31.8%) and (partial) skin necrosis (23.7%) most prevalent. Regarding wound closure, STSG coverage without NPWT was associated with the highest morbidity and a complication rate of 91.0%. Despite being limited in sample size, the two-stage closure, despite larger skin defects, showed complication rates comparable to one-stage closure with NPWT. Multivariate analysis identified STSG with NPWT (OR 0.1 [0.01; 0.4], p = 0.002) and two-stage closure (OR 0.1 [0.01; 0.5], p = 0.01) as protective factors for wound healing complications. Donor site morbidity following FFF harvest with skin paddles is significantly impacted by closure technique. Wound management using one- or two-stage STSG with NPWT is preferred. Initial results of the two-stage closure indicate potentially beneficial outcomes for extensive defects and warrant further prospective validation.

Diabetic wounds suffer from delayed healing due to impaired angiogenesis, bacterial infection, and mechanical damage from dressing changes. This study developed an AP-G-OSA-GB-ICG hydrogel via Schiff base and borate ester bonds. The temperature-responsive conductive system integrates photothermal therapy (PTT) and nitric oxide (NO) release for synergistic antibacterial effects. Graphene oxide-BNN6 (GB) and indocyanine green (ICG) eliminate bacteria via near-infrared (NIR) photothermal effects, while light-triggered NO from BNN6 promotes angiogenesis. Gelatin-based thermal responsiveness enables body temperature-triggered adhesion switching to reduce neotissue damage. Graphene oxide (GO) endows electrical conductivity for potential physiological signal monitoring. In type 1 diabetic SD rats, the hydrogel with NIR irradiation and NO release achieved 100% wound closure at day 14. Masson trichrome staining showed orderly collagen fiber deposition, CD31 and α-SMA immunostaining confirmed a significant increase in vessel density. Hematoxylin and eosin (H&E) staining further revealed the absence of significant inflammatory cell infiltration. This multifunctional system integrates antibacterial activity, angiogenesis promotion, intelligent adhesion, and physiological monitoring, offering a mechanistically innovative and clinically translatable strategy for diabetic wound precision treatment.

Lippia nodiflora leaves have been traditionally used by healers in Silent Valley, Palakkad district of Kerala, for treating wounds. This study aimed to scientifically validate the wound-healing potential of the methanol extract of L. nodiflora leaves (MELN) to support its ethnopharmacological claims. Phytochemical profiling using UPLC-QTOF-MS identified key constituents, and network pharmacology analysis revealed potential pathways and targets involved in wound healing. These findings were further supported by molecular docking, in vitro, in vivo, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) analyses. No toxicity was observed in either in vitro or in vivo models. Network pharmacology indicated that MELN may act through the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance pathway. Core compounds such as quercetin, 3-methylherbacetin, eupafolin, 6-hydroxyluteolin 3'-methyl ether 7-sulfate, and syringic acid beta-glucopyranosyl ester likely contribute to the wound-healing activity, as supported by docking studies. RT-qPCR analysis demonstrated upregulation of genes related to cell migration and proliferation. In vitro assays showed enhanced cell proliferation and migration, indicating pro-healing properties. In vivo excision wound models confirmed significant wound closure, complete epithelialization, and improved histopathological features in MELN-treated groups. Overall, this study provides scientific evidence supporting the ethnopharmacological claim of L. nodiflora in wound management and establishes MELN as a potential herbal formulation for wound healing.

Background: Brain microvascular endothelial cells (BMECs) are essential for maintaining blood-brain barrier (BBB) integrity and cerebrovascular homeostasis. Mitochondrial dysfunction is increasingly recognized as a contributor to vascular pathology in neurodegenerative diseases. While rotenone, a mitochondrial complex I inhibitor, is known to induce oxidative stress in neurons, its effects on BMEC function remain poorly defined. Objective: To investigate how mitochondrial oxidative stress affects BMEC migration and angiogenic capacity, and whether targeting mitochondrial ROS with mitoTEMPO can reverse these effects. Methods: Human brain endothelial cells (HBECs; passage 8) were treated with 0.5 µM rotenone in the presence or absence of 10 µM mitoTEMPO for twelve hours. Cell migration was assessed using a wound healing assay, and angiogenic function was evaluated via Matrigel tube formation. Mitochondrial membrane potential (ΔΨm) was measured using TMRE uptake. Wound closure and tube length were quantified using ImageJ. Statistical analysis was performed using one-way ANOVA with Tukey’s post-hoc test. Results: Rotenone significantly impaired HBEC migration, reducing wound closure by 4.39-fold compared to control (Rotenone: 20.9 ± 4.4%; Control: 4.75 ± 2.45%; p = 0.023, n = 3–4 wells). MitoTEMPO co-treatment significantly improved migration ( p &lt; 0.05 vs. rotenone). In the tube formation assay, rotenone reduced total tube length by 45% ( p = 0.000). Co-treatment with mitoTEMPO partially rescued tube formation, showing a 31% improvement (trend-level, p = 0.058). Notably, mitoTEMPO did not restore the rotenone-induced loss of mitochondrial membrane potential, suggesting that its protective effects are independent of ΔΨm. Conclusions: Mitochondrial ROS impairs endothelial migration and angiogenesis in brain endothelial cells. MitoTEMPO partially rescues these functions, despite persistent mitochondrial membrane depolarization. These findings suggest that mitochondrial oxidative stress, rather than loss of ΔΨm, plays a primary role in BMEC dysfunction and may represent a therapeutic target in cerebrovascular disease.

Rationale: Right ventricular (RV) function is the major determinant of survival in pulmonary hypertension (PH); however, no RV-directed therapies exist. Apelin is a secreted peptide that plays a vital role in cardiac cellular homeostasis, but its role in RV remodeling remains unexplored. Hypothesis: Apelin signaling is protective against RV failure through the inhibition of Renin Angiotensin Aldosterone System (RAAS) signaling and activation of ACE2 signaling. Methods: RV failure was induced in Sprague Dawley rats by pulmonary artery banding (PAB) for 10 days or 10 weeks or by Sugen/hypoxia (SuHx). A subset of PAB or SuHx rats were treated with Pyr-Apelin-13 (200ug/kg/day) or an APLNR antagonist, ML221 (2mg/kg/day). Pressure-volume loops, RV function and molecular changes were assessed. In vitro characterization of apelin signaling was performed in RV endothelial cells (RVECs). RAAS and ACE2 pathway activity were assessed by ACE1, ACE2, MAS1, and AT1R expression via qRT-PCR and Western blot. Angiogenic potential was measured using a Matrigel tube formation, scratch assay, and survival assay. To test the role of apelin and ACE2 signaling, cells were treated with +/1 Pyr-Apelin-13 (100nM, 24hrs), +/- Apelin receptor antagonist ML221 (100uM, 24hrs) or +/- ACE2 inhibitor MLN4670 (100 nM, 24hrs). p&lt;0.05 was considered statistically significant. Results: Pyr-Apelin-13 prevented PAB-induced decreases in cardiac output (CO) and cardiac index (CI) at both 10 days and 10 weeks and preserved RV-PA coupling (Ees/Ea). Pyr-Apelin-13 reduced PAB-induced collagen deposition, cardiomyocyte surface area, and preserved capillarization. In RVECs, Pyr-Apelin-13 enhanced angiogenesis by ring formation, wound closure and cell survival but this effect was blocked by co-treatment with ML221 or MLN4670. Pyr-Apelin-13 upregulated mas receptor (MAS1) and downregulated angiotensin II type 1 receptor (AT1R) vs control. Apelin decreased angiotensin converting enzyme 1 (ACE1 ) and increased ACE2 expression. Pyr-Apelin treatment was able to partially restore ring formation in SuHx RVECs and this was blocked by co-treatment with the apelin receptor antagonist, ML221 or with ACE2 inhibitor MNL4670. Conclusion: Loss of apelin signaling results in more severe RV failure. Identification of pathways and targets engaged by Apelin during RV failure will allow for the development of novel, long-acting and targeted treatment strategies for RV failure.

When a percutaneous metallic implant breaches the skin barrier, the lack of peri-implant soft tissue sealing arising from a foreign body reaction and epithelial downgrowth results in delayed wound healing and closure. This facilitates microbial pathogen entry, leading to infection, inflammation, and ultimately, peri-implantitis. Toward this end, bioglue formulations of -human hair keratin (HHK) and chicken feather keratin coupled with polyphenols, dopamine (DOPA), quercetin (Q), and tannic acid (TA) were developed for peri-implant soft tissue sealing. A freeze-thaw gelation mediated by thiol recombination of reduced keratins was employed for attachment of soft tissue (porcine intestine) to titanium. Lap shear tests revealed that the adhesion strength of reduced keratins improved with polyphenol addition, with a maximal glue strength exhibited by HHK + TA (10:1 w/w) when applied between the porcine intestine and titanium. Rheological characterization ascertained shear-thinning behavior and injectability of the glues into wet aqueous media and dry surfaces. Despite inferior glue strength to commercial ethyl 2-cyanoacrylate bioglue, the keratin ± polyphenol glues were more skin compatible, evidenced by greater viability and proliferation of immortalized human skin epidermal keratinocytes (HaCaT) and equine dermal fibroblasts (E. Derm NBL6). Furthermore, the antioxidant activity of keratin ± polyphenol glue formulations conferred greater anti-inflammatory activity in bacterial lipopolysaccharide stimulated RAW 264.7 murine macrophages. Taken together, the application of keratin ± polyphenol glues for soft tissue sealing may be a promising approach to mitigate peri-implantitis around transcutaneous metallic prostheses.

Aim Treatment of bone infections includes debridement, specific antibiotic therapy, and effective wound coverage, often requiring flap surgery. The superiority of fasciocutaneous or muscle free flaps, remains unanswered. Hence these flaps are interchangeably applied to cover complex tissue defects and osteomyelitis. We aimed to establish a porcine flap model and evaluate its potential to assess the tissue-healing efficacy of fasciocutaneous and muscle flaps. Method Using both hindlegs of 10 pigs, symmetric tibial bone and soft tissue defects were created and covered with either fasciocutaneous flaps (n=8), muscle flaps (n=8), or primary wound closure (n=4) as controls. Ischaemic metabolites (glucose, lactate, and pyruvate) were sampled with microdialysis in the flaps and subcutaneous control tissue for 11h before, during, and after 60 min of global flap ischemia (simulating free flaps). Flap histopathology with grading of the acute inflammatory response was performed. Results All pigs and flaps completed the study. During ischemia, we found rapid decreases in glucose and glucose-lactate ratio levels and increases in lactate and lactate-pyruvate ratio levels in both flaps. This was followed by secondary reversed reperfusion changes, with the most labile kinetics in the muscle flaps during ischemia and in the fasciocutaneous flaps during late reperfusion. The histopathological mean inflammatory parameters were increased in the fasciocutaneous flaps compared to the muscle flaps. Conclusions We successfully established a robust and reproducible flap model for evaluating ortho-plastic reconstructions. Following 60 minutes of flap ischemia, then reperfusion, we demonstrated increased tissue structural changes with a slower metabolic rate and a possible shift towards an ischemic state in the fasciocutaneous flaps compared to muscle flaps. Flap-dependent differences in metabolic patterns and acute inflammatory responses may have important implications for the bone healing and anti-infective microenvironment underneath. Next, we will apply the model to assess fasciocutaneous versus muscle flaps in a long-term- and an osteomyelitis setup.

Marine algae are a sustainable and eco-friendly resource, growing rapidly without freshwater or arable land while aiding carbon sequestration. Their extract is rich in biodegradable polysaccharides like alginate, fucoidan, carrageenan, agar, and Ulvan which can be used further in wound healing thanks to their unique characteristics such as ensuring moisture balance and tissue regeneration by forming biocompatible hydrogels with antimicrobial, anti-inflammatory, and antioxidant properties, key requirements in wound healing. The present study explored the utilization of local grown marine algae (i.e., Aegean seashores from Türkiye) and transforming the waste into useful end-products for dermatocosmetics and healing systems. The extracted polyssacharide, e.g., Ulvan which was characterized by means of FT-IR spectroscopy, DSC, and antioxidant activity, was included inside a semi-solid formulation and combined with other polysaccharides from other natural sources such a chitosan, alginate, and hyaluronic acid to form bioactive hydrogels with wound closure activity. The formulated hydrogels exhibited significant swelling capacity, antioxidant activity, and the selected optimal formulation exhibited enhanced wound closure rates in vitro, demonstrating potential for wound-healing applications.

Comparative evaluation of wound closure and healing following periodontal flap surgery using silk sutures and N-Butyl cyanoacrylate tissue adhesive in stage II/III periodontitis: A short-term clinical study

Introduction Wound healing and skin regeneration have become global health challenges, causing substantial harm to the physical and mental health. Many studies have shown that human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) can promote tissue repair and regeneration. However, the efficacy and underlying mechanisms of hUCMSC-Exos in treatment remain to be elucidated. Methods hUCMSC-Exos were isolated by ultracentrifugation and characterized by analyses of nanoparticle tracking analysis (NTA), western blotting (WB), and transmission electron microscopy (TEM). The efficacy of hUCMSC-Exos on the proliferation, migration, and angiogenesis potential of fibroblasts and endothelial cells were examined in vitro . The effects of the hUCMSC-Exos on wound healing were assessed by wound closure rate, histological and immunohistochemical analyses. miRNAs and their target genes that may play a role in skin repair and regeneration were identified and predicted through bioinformatics analysis. Results In vitro analysis indicated that hUCMSC-Exos are easily internalized by human umbilical vein endothelial cells (HUVECs) and human skin fibroblasts (HSFs), significantly promoting the proliferation and migration of HSFs, as well as the proliferation and tube formation of HUVECs. Analysis of skin wound models indicated that hUCMSC-Exos significantly accelerate wound healing by reducing inflammation, stimulating angiogenesis, and promoting the formation of extracellular matrix. Mechanistically, bioinformatics analysis suggests that Unc-51-like autophagy activating kinase 2 (ULK2), Collagen Type XIX Alpha 1 Chain (COL19A1), and Interleukin-6 Signal Transducer (IL6ST) are potential key molecules involved in the regulation of wound repair by hUCMSC-Exos. Discussion In summary, hUCMSC-Exos regulate the functions of HUVEC and HSFs through miRNA, significantly promoting wound healing and tissue repair, suggesting that hUCMSC Exos therapy is a promising therapeutic approach.

BackgroundRapid and efficient epithelial regeneration is fundamental for tissue homeostasis and proper function. As the outermost ocular structure, the cornea is transparent, multilayered, and vital for clear vision. Due to its exposed position, the cornea frequently undergoes various forms of injury affecting either the epithelium itself or its surrounding microenvironment, including corneal innervation and the tear film. Corneal abrasion, occurring commonly through trauma or as part of refractive surgical procedures, is typically viewed as a minor event since it usually resolves rapidly. Consequently, the cornea serves as an excellent model for studying epithelial wound healing. However, complications such as persistent epithelial defects or corneal opacity can develop, underscoring critical gaps in understanding the underlying molecular mechanisms.MethodsUtilizing a unilateral corneal abrasion mouse model, we conducted a comprehensive multi-omics analysis, integrating transcriptomics, proteomics, and epitranscriptomics, to dissect the dynamic molecular responses post-injury in both wounded and contralateral tissues. To elucidate the role of the tear film, we performed additional studies involving lacrimal gland ablation combined with corneal injury. We applied RNA sequencing to profile transcriptomic changes in corneal and lacrimal gland tissues, and mass spectrometry to study tear proteomics and epitranscriptomic modifications.ResultsWe revealed a major modulation of the cornea transcriptome after abrasion, suggesting a regulation of pathways including JAK-STAT, Wnt and TGF-β, and a reduction of nucleoside modifications. The lacrimal gland transcriptome and tears proteome were also significantly affected. Plus, we highlighted a bilateralization, both in the cornea transcriptome and tears proteome. In the tear-deficient conditions, the wound closure rate and molecular responses were altered, and the bilateralization was impacted, with an increased matrix remodeling and a modulation of keratins expression.ConclusionsOur multi-omics analyses revealed extensive epithelial cellular plasticity as a key mechanism driving rapid wound closure, characterized by profound remodeling of transcriptional networks and RNA modifications. Importantly, we uncovered a previously underappreciated role of the lacrimal gland and tear film in mediating bilateral molecular responses following unilateral injury, emphasizing their pivotal roles in tissue regeneration. Additionally, we identified novel regulatory roles for RNA methylation events and critical signaling pathways implicated in epithelial healing.Graphical abstractSupplementary InformationThe online version contains supplementary material available at 10.1186/s11658-025-00804-9.

The aim of this clinical trial was to evaluate the performance and local tolerance of an innovative mesh-free contact layer (healing matrix) made of lipidocolloid technology (TLC) in the management of various wounds. This dressing is made highly flexible by the absence of textile mesh in its core. A four-week, prospective, multicentre clinical trial was conducted on the evaluated dressing (UrgoFit, Laboratoires Urgo, France) in 23 centres in France. Eligible patients were adults with a cutaneous wound of acute or chronic origin or due to epidermolysis bullosa (EB) in the granulation stage. The primary endpoint was the relative wound area reduction (RWAR) at week 4. Secondary endpoints included wound closure rate and time-to-heal, as well as dressing change frequency, pain at dressing removal, local tolerance and acceptability of the dressing. A total of 78 adult patients (23-95 years old) were treated with the dressing over a period of 24±8 days. Wound aetiologies included: postoperative or traumatic finger wounds; skin graft donor sites; dermabrasions/skin tears; burns; leg ulcers (LUs) of predominantly venous origin; a stage 3 pressure injury; and EB lesions. The median RWAR at week 4 was 98.2% (ranging between 61.5-100.0%, depending on wound types). Complete closure was achieved in 49% of patients (59% in acute wounds, 60% in EB lesions and 16% in chronic wounds) with a median time-to-heal of 16.5 days (ranging between 14.5-27.0 days, depending on wound types). Half of LUs reached a RWAR ≥40% at week 4, a predictive indicator of complete wound healing at week 24. Dressings were changed every 2±1 days on average (and left in place for a maximum of 10 days). Since the first application, the dressing was judged by healthcare professionals (HCPs) to be 'very easy' or 'easy' to apply on 96% of wounds, with a 'very good' or 'good' conformability to 94% of wound beds. Similar results were reported in cases of finger/hand wounds. Since the first week of treatment, the dressing removal was also judged 'very easy' or 'easy' in 95-98% of the cases, protecting and preserving newly formed tissue in 100% of cases. At the first follow-up visit, patients reported the dressing changes to be painless in 95% of cases. This represented a significant improvement over the previous dressings they received (p<0.0001). In all, seven non-serious adverse events related to the dressing were reported during the study period. In this clinical trial, the innovative mesh-free TLC dressing was shown to promote wound healing, to be well tolerated and well accepted by patients and HCPs, in line with the evidence available on other TLC dressings; however, its enhanced conformability may provide an additional benefit for the management of wounds.

Lower limb assessment, patient adherence to treatment and timely initiation of compression therapy are major issues for most healthcare services managing patients with leg ulcers (LUs). Various guidelines recommend that if a patient has a LU and no 'red flag' symptoms, then 'mild' or 'reduced' compression therapy (20mmHg) is better than no compression while they await an ankle-brachial pressure index (ABPI), or if patients with a venous leg ulcer (VLU) cannot tolerate prescribed high compression therapy (40mmHg). The aim of this clinical study was to document the performance of a multicomponent bandage compression system applying reduced pressure in real-life practice, as recommended in national guidance. A retrospective, multicentre, non-comparative clinical study was carried out within community settings in the UK. Eligible patients were consecutive adult outpatients with a VLU (or suspected VLU) treated with the evaluated compression system (UrgoKTwo Reduced; Laboratoires Urgo, France), after 'no red flags' for reduced compression therapy were identified. The primary endpoint was the rate of complete ulcer closure by week 12. Main secondary endpoints included time-to-heal in days, oedema resolution, patient adherence and local adverse events (AEs). Data from 102 patients (35-99 years old, 60% female, 58% overweight or obese) who had been treated with the evaluated compression system for an average period of 50±32 days were included in this clinical study. The prescription of the compression system was justified for 84% of patients by poor tolerance of high compression, and for 16% by the absence of a complementary vascular examination (ABPI). UrgoStart Plus dressings (Laboratoires Urgo, France) were combined with the compression system in 43% of wounds, while antimicrobial dressings were frequently applied in cases of local wound infection. During the treatment period, patient adherence to compression therapy was rated 'very good' or 'good' in 99% of cases (wearing the compression bandages 24 hours a day until the next nurse visit). By the end of the treatment period, 75% of wounds healed, with a median time-to-heal of 45 days (interquartile range: 33 days, 63 days), 23% improved and 2% worsened. The highest wound closure rates were achieved in cases of recent wounds or wounds treated with the UrgoStart Plus treatment range (91% and 89%, respectively). The shortest healing times were observed with smaller wounds or those treated with UrgoStart Plus dressings (13 and 10 days sooner, respectively). By the final visit, oedema was resolved in 63% of patients who had oedema at baseline. Once their ulcer healed, 75% of patients received subsequent compression hosiery to prevent ulcer recurrence. Throughout the study period, only one AE was documented by the healthcare professionals: a local wound infection, unrelated to the compression system evaluated, but for which compression therapy was discontinued because of the associated pain. These findings are consistent with previous evidence available on this reduced compression system and support its use as a first-line treatment in patients with a suspected VLU until a full vascular assessment indicates that stronger compression is appropriate, as well as in patients who are unable to tolerate high compression therapy.