Wounds can result from a variety of causes, including burns, traumas, surgeries, and long-term conditions like diabetes. The development of biofilms has detrimental consequences as well. Wound healing is also impacted by ageing, hypertrophic scarring, and recurrent injuries. With rising death rates and related costs, wound healing is a serious global concern. The severity of wound healing is caused by microbial infection, inflammation, and a lack of cell migration, proliferation, and angiogenesis. The many phases of wound healing include hemostasis, inflammation, proliferation, and remodeling to restore the integrity of the skin and subcutaneous tissue with its anti-microbial, anti-angiogenic, and anti-inflammatory effects. The development of biomaterials for wound dressings has reached a new benchmark and improved understanding. The extraordinary outcomes are caused by more recent discoveries and patents that concentrate on the wound microenvironments, such as pH, temperature, and reactive oxygen species. Because they can adjust to the current microenvironment at the injured surface, wound dressing materials that can function as theranostics also have significant advantages. The wound healing products should concentrate on cell-cell interactions, cell proliferation, cell signaling, and vascularization in order to make the therapy effective. The main advantages are also explained by the wound-healing material's penetrating effect. This review endeavored to throw light on different aspects of wounds and the latest advances in bioproducts effective for wound healing. Further, the clinical trials for wound healing products have been addressed.
Introduction: Chronic wounds and pathologic scars remain a persistent challenge in plastic surgery. Conventional treatments can be costly and inconsistent, prompting interest in regenerative approaches that utilize autologous tissue. Emulsified fat produces nanofat through mechanical processing and contains adipose-derived stem cells, stromal vascular fractions, extracellular matrix proteins, cytokines and growth factors. The purpose of this systematic review is to evaluate the use of autologous nanofat for wound healing and scar management, with emphasis on preparation techniques, treatment indications, and outcomes. Methods: A comprehensive PubMed search with no date restrictions was conducted in January 2026 using MeSH terms and keywords related to nanofat and wound-healing applications. Studies were screened independently by two reviewers using the Rayyan platform. Eligible studies evaluated nanofat for wound healing in human or animal subjects; non-English articles, studies not involving nanofat, editorials, and conference abstracts were excluded. The extracted data included study characteristics, participant numbers, treatment details, indications, adjunct therapies, follow-up duration, outcomes, and complications. Studies were grouped by clinical application, with individual reports included in multiple categories when relevant. Results: The search identified 53 records, of which 22 studies met the inclusion criteria after screening. These included 20 human and two animal studies spanning randomized controlled trials (n = 3), prospective trials (n = 6), retrospective analyses (n = 6), case series (n = 4), and case reports (n = 3). Mechanical emulsification was the predominant autologous nanofat preparation method (91%), often combined with filtration or centrifugation. Clinical indications in human studies were diverse, most commonly including scar treatment (n = 14) (acne, burns, depressed, and post-surgical), followed by chronic wounds (n = 3) and reconstructive applications (n = 3). Nanofat was administered via injection in 86% of studies (n = 19), typically using fine-gauge needles or microcannulas with intradermal or subdermal placement, while three studies used non-injection approaches such as topical, membrane, or dressing-based delivery. Scar or aesthetic parameters, measured using VSS, POSAS, physician grading, photography, pigmentation analysis, or clinical appearance, were evaluated in 73% of studies (n = 16), and all reported improvement in variables such as pigmentation, pliability, thickness, texture, or overall appearance. Wound-healing endpoints were assessed in 36% (n = 8), with 100% (n = 8) demonstrating accelerated healing, improved epithelialization, or defect closure. Patient-reported outcomes, including satisfaction or quality of life, were measured in 32% (n = 7), and all showed improvement. Objective imaging modalities (e.g., 3D imaging, ultrasound, angiography, digital analysis) were used in 23% (n = 5), each confirming structural or physiologic improvement. Histologic or biomolecular analyses were performed in 27% (n = 6) and uniformly demonstrated regenerative changes, such as increased angiogenesis, collagen remodeling, or growth factor expression. Treatment was well tolerated, with 77% of studies (n = 17) reporting minimal or no complications and only transient mild adverse effects, including mild pain, bruising, erythema, and edema. Conclusions: Current evidence suggests that autologous nanofat is a promising regenerative therapy for wound healing and scar modulation. Across diverse clinical applications, nanofat has been associated with improved tissue quality, enhanced healing, and favorable patient-reported outcomes, with minimal complications. The mechanical processing of autologous tissue may also involve fewer regulatory concerns compared with more extensively manipulated cellular products.
Although Negative Pressure Wound Therapy (NPWT) has been increasingly used in wound care to improve impaired healing, there is little scientific evidence supporting its role and underlying biomolecular mechanisms. Aims of the present study are to provide a quantitative analysis of recent literature investigating NPWT in diabetic wound healing focusing on healing duration, wound closure, hospitalisation period and complications, and qualitative insight into studies analysing biomolecular mechanisms. The systematic review and meta-analysis were conducted following PRISMA guidelines (PROSPERO: CRD42024524813). 21 studies published in PubMed, Cochrane Library, EMBASE between 2019 and 2024 were included. Clinical studies indicated NPWT was superior to standard care dressings (SCD), promoting faster wound healing with significantly reduced hospitalisation times by 7.8 days (95% CI: -14.2 to -1.4, p = 0.017), and significantly reduced complications rates, particularly major and minor amputations (95% CI: -10.2 to -1.3, p = 0.01). Mechanistic in vitro and animal studies highlighted NPWT can reduce local inflammation, oxidative stress, support angiogenesis and improve scarring, essential components of normal healing. Although studies suggest NPWT is more effective than SCD for diabetic wound healing, the paucity of studies, small cohorts and scarce outcomes consistency make defining clear conclusions challenging. There is still more evidence required to fully understand NPWT's role in the complex diabetic wound healing.
Deep burns in pediatric population often require split-thickness skin grafts (STSGs) and the identification of an optimal donor site is crucial to minimize morbidity, accelerate healing and reduce short- and long-term complications. The scalp appears to be increasingly used in clinical practice, but evidence remains limited, despite the promise of novel bioengineering and regenerative approaches. A systematic review about the use of scalp for STSG in pediatrics was conducted across PubMed, Scopus, and Cochrane (2005-2025). Clinical outcomes considered were donor-site healing time, early and late complications, perioperative practices, and quality of scars. Four studies met the inclusion criteria (n = 417, mean age 2.9-7.3 years) with follow-up periods up to 27 years. Epithelialization occurred between 7 and 25 days. Early complications included folliculitis (up to 44% in certain hair types) and delayed healing (n = 13; 52%). A rigorous harvesting technique is needed to avoid preventable complications. Late sequelae included alopecia (1.6% to 33%-the latter largely unperceived by patients) and hypertrophic scarring (1.6-4%). Scar quality was rated good in >80% of cases. Evidence supports the scalp as a safe, efficient, and cosmetically favorable donor site for pediatric STSG. Based on evidence and clinical experience, we propose the first structured scalp-donor management algorithm to optimize safety, reduce complications, and standardize perioperative care in the management of pediatric burns.
Burn injuries impose a significant global health burden, particularly in low- and middle-income countries where access to surgical interventions is limited. In such settings, supportive measures, especially nutrition, play a central role in recovery. We report the case of a 30-year-old man with ∼70% total body surface area scald burns, including superficial and deep partial-thickness injuries. On admission, he was hemodynamically stable but at high risk for malnutrition. Multidisciplinary care included fluid resuscitation, antimicrobial dressings, antibiotics, and early nutrition. Energy and protein goals were set at 3400 to 3800 kcal/day and 153 to 212 g/day, respectively. By day 4, oral intake achieved ∼3500 to 3700 kcal/day and 178 to 205 g protein/day. The patient showed rapid healing of superficial burns (50%-55% total body surface area by postburn day 19) and complete wound closure at 5 months, without grafting. One-year follow-up revealed no major complications, although expected scarring and contractures occurred. In conclusion, aggressive nutritional support potentially achieved favorable outcomes in this burn patient. Early nutritional support (3500–3700 kcal/day, 178–205 g protein) accelerated 50% to 55% total body surface area wound closure by postburn day 19 in a 30-year-old man.Personalized nutrition prevented severe malnutrition, supporting spontaneous healing of deep partial-thickness burns by 5 months.A protein intake of 1.8 to 2.5 g/kg is safe for burn patients and does not have hepatic or renal consequences.
Wound healing is a complex process involving hemostasis, inflammation, proliferation, and remodeling. Chronic wounds (persisting beyond 6 weeks) and pathological scarring pose significant clinical challenges. These conditions not only impair patient quality of life but also impose heavy economic burdens on healthcare systems. BoNT/A has been widely studied and shows promise in promoting wound healing, reducing pathological scarring, and improving chronic wounds. However, the existing evidence base largely consists of low-level studies, including animal models, case reports, and small clinical trials. While these studies show positive outcomes, their efficacy and long-term safety need to be validated through high-quality large-scale clinical trials. Therefore, it is important to acknowledge the limitations of current evidence and emphasize the need for further research to provide more robust support. To comprehensively review the potential roles and underlying mechanisms of BoNT/A in promoting wound healing, preventing pathological scarring, and treating chronic wounds, aiming to provide theoretical insights for clinical applications. This review synthesizes existing literature on BoNT/A, focusing on its biological mechanisms in wound healing, including effects on inflammation, angiogenesis, fibroblast activity, and extracellular matrix (ECM) regulation. It also summarizes clinical evidence and combination therapies involving BoNT/A for adverse wound outcomes. A literature search was conducted in PubMed, Embase, and Web of Science using the terms "botulinum toxin A", "wound healing", "scar", and "chronic wounds". Publications from the past ten years were prioritized, with earlier landmark studies included when relevant. Both preclinical and clinical evidence was considered to provide a comprehensive overview. BoNT/A exerts multifaceted effects: it inhibits inflammatory responses by reducing mediators like IL-6 and substance P; promotes angiogenesis via HIF-1α/VEGF and nitric oxide pathways; modulates fibroblast activity by suppressing TGF-β1/Smad and ERK signaling to reduce abnormal collagen deposition; and improves wound microenvironment by reducing tension and regulating sweat/sebum secretion. Combination therapies (e.g., with steroids, lasers, or hyaluronic acid) enhance efficacy in scarring and chronic wound treatment. BoNT/A has been widely studied and most reports suggest a favorable short-term safety profile; however, current evidence is predominantly low-level (animal studies, case reports, small series) and all wound-care uses remain off-label, underscoring the need for adequately powered randomized trials and long-term safety data. 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 .
The relationship between transepidermal water loss (TEWL), scar parameters (such as elasticity and colour), and time has not been comprehensively explored. This study aimed to elucidate the association between scar activity and TEWL in burn scars resulting from delayed healing and skin grafting, while also investigating temporal trends. Forty skin-grafted scars and forty delayed-healing scars were assessed for TEWL, colour, and elasticity using a combination of objective and subjective measurement tools. Matched uninjured skin areas were included as controls. The results revealed that delayed-healing scars exhibit significantly higher TEWL than skin-grafted scars, both of which demonstrate elevated TEWL compared to normal skin. TEWL levels in skin-grafted scars normalized at approximately 9.1 months post-injury, whereas delayed-healing scars required nearly 15 months to normalize. Increased TEWL was positively correlated with higher POSAS-O scores, vascularity, erythema, and elasticity measurements. Comparison of two TEWL measurement devices showed strong similarities overall, but notable variations at the extremes of the measurement range existed. This study uniquely quantifies and elucidates the relationship between TEWL and scar parameters in the two distinct types of burn scars. The results highlight the positive correlation between TEWL and both subjective and objective measures of scar activity, suggesting TEWL as an indicator of scar progression. These findings position TEWL as an essential metric in scar management, offering valuable guidance for the effective use of silicone gel sheets and moisturizers to regulate and optimize scar progression.
Background/Objectives: Burn wounds are complex injuries associated with extensive inflammation, extracellular matrix (ECM) damage, and a high risk of impaired tissue remodeling and scarring. Modern wound dressings are expected not only to protect the wound bed but also to actively support the healing process. Biodegradable polymer-based nonwoven dressings incorporating natural bioactive compounds, such as propolis, may favorably influence wound repair. The aim of this study was to evaluate the effect of propolis-containing biodegradable, nonwoven poly(lactide-co-glycolide) (PLGA) dressings on the dynamics of dermatan sulfate and chondroitin sulfate content during burn-wound healing. Methods: The present study investigated temporal alterations in sulfated glycosaminoglycans (GAGs), including dermatan and chondroitin sulfates, during the healing of experimentally induced burn wounds in white domestic pigs treated with biodegradable, nonwoven poly(lactide-co-glycolide) (PLGA) dressings containing 5 wt% or 10 wt% of propolis. Control tissue samples were obtained from wounds treated with physiological saline or nonwoven PLGA dressings without propolis. Quantitative analysis of GAG content was performed on days 0, 3, 5, 10, 15, and 21 of the healing process using enzyme-linked immunosorbent assay (ELISA). Statistical differences between groups were assessed by one-way multivariate analysis of variance (MANOVA) followed by Tukey's post hoc test. Results: Propolis-containing biodegradable nonwoven PLGA dressings significantly increased dermatan sulfate and chondroitin sulfate content in the burn wound bed compared to control treatments. The effect was observed at multiple time points and was more pronounced for dressings containing 10 wt% of propolis than for those containing 5 wt%. Conclusions: Biodegradable nonwoven PLGA dressings incorporating propolis modulate glycosaminoglycan dynamics during burn-wound healing, indicating enhanced extracellular matrix remodeling and supporting their potential use as bioactive burn wound dressings.
Hypertrophic scarring is characterized by excessive dermal fibrosis and irregular collagen metabolism, mediated by fibroblasts derived from keloids. This condition typically arises from improper wound healing after deep burns, trauma, or surgical procedures. Although intralesional injections of botulinum toxin type A and 5-fluorouracil are common clinical treatments, their effectiveness is often limited by temporary drug retention, insufficient penetration depth, and complications from repeated injections. To overcome these challenges, we developed an injectable composite hydrogel system, F@P-B-SilMA, to promote scarless wound healing. Systematic characterization revealed that this system undergoes rapid UV-initiated in situ polymerization and exhibits a three-dimensional porous microstructure. It also demonstrates excellent tissue adhesion and mechanical compliance, along with favorable rheological properties, and tunable degradation kinetics that align with the various phases of wound healing. These attributes collectively meet the essential criteria for advanced wound dressings. Comprehensive in vitro and in vivo evaluations confirmed the system's biocompatibility and its dual ability to accelerate wound closure while suppressing fibrotic proliferation. The injectable F@P-B-SilMA composite hydrogel system represents a promising therapeutic approach for clinical scar management, showcasing significant potential as a next-generation wound dressing for scarless tissue regeneration.
Corneal alkali burns frequently lead to severe pathological manifestations (including oxidative stress and inflammatory response) and dysregulated matrix remodeling-associated stromal fibrosis. Current treatments mainly target inflammation but remain insufficient for preventing fibrotic scarring and enhancing corneal clarity. To address this limitation, a natural anti-fibrotic proteoglycan i.e., decorin (DCN) was conjugated to quaternary ammonium (QA)-modified nanoceria (Ce) as multifunctional metallic therapeutics (Ce-QA/DCN). The biofunctionalized nanomaterials exhibited favorable physicochemical stability and good ocular biocompatibility. Our results demonstrated that the conjugated DCN can preserve its ability to inhibit collagen fibrillogenesis and downregulate fibrosis-associated signaling pathways. In a rat model of alkali burns, topical administration of Ce-QA/DCN markedly improved corneal tissue transparency and promoted stromal architectural restoration as compared with conventional pharmacological treatment (dexamethasone). The combination of ceria-mediated redox regulation and DCN-mediated fibrotic inhibition enables simultaneous alleviation of pathological manifestations and enhancement of matrix remodeling during corneal wound healing. In summary, the biomaterial-based nanomedicine may provide a promising therapeutic strategy for managing severe corneal injuries and fibrosis-related ocular surface disorders. STATEMENT OF SIGNIFICANCE: Owing to their tunable surface properties and intrinsic biological activities, metallic nanomaterials have been considered promising platforms for ocular delivery and therapy; however, achieving effective corneal epithelial penetration while simultaneously regulating complex ocular pathological process remains a major challenge. This work presents the first report on rational design of ceria-based (quaternary ammonium/decorin-functionalized) nanotherapeutics for tailoring the structure-function relationships toward effective treatment of corneal alkali burn. Integrating cationic interface engineering with antagonist conjugation is demonstrated to critically govern permeability and biocompatibility of nanoparticles, indicating that the optimized formulations can enhance epithelial barrier penetration and inhibit stromal oxidation/inflammation/fibrosis. In vivo, such a biomaterial design achieves ∼92% reduction in corneal haze, highlighting its potential for treating eye injuries and promoting tissue remodeling.
Microstomia is defined as a small mouth size that interferes with daily activities. No protocol has been established for microstomia caused by facial burns. This study aimed to confirm the clinical usefulness of a patient-customized mouthpiece using 3D scanner modeling and printing technology. Each participant's mouth was scanned using a 3D scanner and the scanned model was imported into modeling software. After modeling the mouthpiece to fit the maximum horizontal and vertical lengths of the mouth and the thickness of the lips, it was manufactured using a 3D printer. The participants were monitored while wearing the mouthpiece for more than 12 h a day, including 8 h of sleep. As the primary outcome, the vertical and horizontal distances of the mouth were measured before and after wearing the customized mouthpiece for 2 months. As secondary outcomes, biological scar properties, Vancouver Scar Scale (VSS) scores, and Patient and Observer Scar Assessment Scale (POSAS) scores were evaluated. Five patients with burns on the upper, lower, left, and right sides of the mouth who underwent skin grafting were included in this study. The patients had contractures in all directions. Comparing measurements before and after 8 weeks of wearing the mouthpiece, the distances (horizontal and vertical) improved from 3.86 ± 0.56 mm and 2.16 ± 0.48 initially to 4.28 ± 0.38 and 2.82 ± 0.77 after wearing the mouthpiece (P = 0.20 and 0.04). Statistically significant improvements were observed in the pliability of the VSS (P = 0.04) and the thickness and overall opinion (P = 0.04) of the POSAS-observer component. In the comparison of biomechanical properties, improvements were observed in scar characteristics, although the differences were not statistically significant (P > 0.05). The application of a patient-tailored mouthpiece using 3D scanner modeling technology for microstomia caused by hypertrophic scars after burns has shown positive effects for improving size and oral function without causing side effects on the scars.
The treatment of burn wounds is a complex and lengthy process, including infection control, inflammation modulation, tissue regeneration, and scar management. Although significant progress has been achieved, numerous clinical challenges persist, especially the increased bacterial resistance, the risk of wound sepsis, and the issue of serious hypertrophic scar. In recent years, nanozymes have emerged as a hotspot in materials research and increasingly been applied to promote burn wound healing. Possessing multiple enzyme-like activities, nanozymes can integrate antibacterial, anti-inflammatory, and pro-angiogenic effects, among others. Meanwhile, nanozymes offer advantages such as less prone to inducing drug resistance, high stability, and simple preparation, which indicate broad application prospects compared with antibiotics, natural enzymes, and traditional nanomaterials. This review provides a comprehensive overview of the pathophysiology involved in burn wounds and introduces nanozymes exhibiting a variety of enzyme-like activities including oxidase (OXD), peroxidase (POD), superoxide dismutase (SOD), catalase (CAT), haloperoxidase (HPO), nitrite reductase (NiRs), and hydrolase. The potential mechanisms by which nanozymes promote burn wound healing are summarized and elucidated from the aspects of anti-bacteria, anti-oxidative stress, anti-inflammation, pro-angiogenesis, and anti-scarring. Finally, we discuss the limitations of the current study and offer an outlook for future research, hoping to pave the way for the next generation nanozymes in the treatment of burn wounds.
Exosomes derived from mesenchymal stem cells (MSCs) have garnered significant research interest for their roles in promoting wound healing and preventing scar formation. Studies have shown that MSC-derived exosomes (MSC-Exos) accelerate the repair of cutaneous and corneal wounds through multiple mechanisms, including modulation of cell migration, anti-inflammatory responses, inhibition of apoptosis, collagen remodeling, and promotion of angiogenesis. Notably, exosomal miRNAs play a pivotal role in inhibiting fibroblast-to-myofibroblast transformation and modulating the TGF-β signaling pathway, thereby effectively reducing scar formation. Promising outcomes of exosomes derived from adipose tissue- and umbilical cord blood-derived MSCs in various wound models underscore their clinical potential. This review systematically elaborates on the specific mechanisms by which MSC-Exos promote wound healing and inhibit scar formation, and summarizes their application outcomes in different wound models. Additionally, it explores current advanced biomaterial delivery systems designed to optimize exosome delivery, aiming to provide insights and future directions for the clinical translation of MSC-Exos. MSC-Exos effectively promote tissue repair and reduce scarring through multi-target and multi-pathway mechanisms, demonstrating significant clinical application prospects. Delivery systems incorporating biomaterials hold promise for further enhancing their therapeutic efficacy and stability. Future research should focus on elucidating the molecular mechanisms of exosome action, developing scalable preparation protocols, and conducting preclinical and clinical evaluations to advance their translation into clinical therapeutic applications.
Atrophic acne scars (AAS) is one of the most common skin sequelae following acne vulgaris. Fractional laser has shown great therapeutic potential in recent years, but there is no recognized wound care standard after laser resurfacing. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has shown its value in many other acute wounds healing. Here, we investigated the efficacy and safety of topical recombinant human GM-CSF after 1927-nm fractional thulium fiber laser (TFL) in AAS treatment. 30 patients were enrolled and treated with TFL, then randomly assigned to rhGM-CSF-containing gel for 7 days or no intervention on each side. Photos, melanin index (MI), erythema index (EI), hydration, transepidermal water loss and improvement of lesions were assessed at 0, 3, 7, 14, 30 and 60 days. 27 patients finally completed the study. Compared to TFL monotherapy, topical rhGM-CSF-containing gel significantly reduced duration of scabbing and skin erythema, and showed milder EI one week after TFL. MI on the rhGM-CSF side exhibited more pronounced decrease at the first and second months after TFL. Patients reported significant differences in sensations of burning, dryness and scabbing between two sides. Both sides yielded improvements in acne scars relative to baseline assessments, but no difference between them. The combination of TFL and topical rhGM-CSF-containing gel showed significantly superior outcomes, manifesting as accelerated wound healing, improved postoperative patient comfort, and a reduced incidence of post-laser pigmentation. 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 .
Background/Objectives: Thermal injuries represent a significant global health burden, often complicated by hypertrophic scarring, chronic inflammation, and delayed re-epithelialization. While Mesenchymal Stem Cell (MSC) transplantation has shown promise, its clinical translation is hindered by risks of tumorigenicity and immunological concerns. This study evaluates the efficacy of cell-free Extracellular Vesicle (EV) therapy-derived from both mammalian MSCs and plant sources (PDNVs)-as standardized, off-the-shelf alternatives. This study synthesizes evidence focusing on re-epithelialization velocity, angiogenic activity, and anti-fibrotic outcomes, while assessing the impact of second-generation delivery scaffolds on therapeutic durability. Methods: Conducted in accordance with PRISMA 2020 guidelines and registered in PROSPERO (CRD420261305379), this review interrogated PubMed, Scopus, Embase, and Web of Science for studies published between 2015 and 2026. Eligible studies included in vivo animal models of thermal injury using purified vesicles from mammalian MSC sources or plant-derived nanovesicles compared with placebo, standard care, or untreated controls. Data were synthesized narratively; methodological quality was appraised using the SYRCLE risk of bias tool and compliance with MISEV guidelines. Results: Synthesis of 50 studies revealed that vesicle-based interventions consistently accelerate wound closure and improve histological healing. Mammalian ADSC-derived vesicles demonstrated superior anti-fibrotic effects via the miR-192-5p and miR-125b-5p axes, while hUC-MSC vesicles attenuated systemic inflammatory signaling via miR-181c. Plant-derived nanovesicles (PDNVs) showed potent antioxidant and re-epithelialization effects, with emerging potential as engineered genetic carriers. Crucially, advanced delivery systems, including bioactive hydrogels and microneedle patches, were repeatedly associated with improved local retention and more durable effects than bolus injections. Conclusions: Vesicle-based therapies show consistent pro-healing signals in preclinical models, suggesting source-dependent profiles: MSC-derived vesicles excel in immunomodulation and anti-fibrotic remodeling, while PDNVs provide a scalable, low-immunogenicity platform. As a cell-free strategy, these therapies circumvent the safety risks of live cell transplantation. This review identifies a critical shift toward second-generation delivery scaffolds to overcome the clearance crisis of topical applications, emphasizing the need for harmonized MISEV-aligned characterization in future clinical translation.
The present work aimed to obtain antibacterial wound dressings using bacterial cellulose (BC) as a support, to improve wound treatment and reduce the incidence of infections. To enhance the antibacterial activity of the synthesized dressings, the introduction of ZnO nanoparticles into the BC network by precipitation was pursued. The method chosen to develop ZnO NPs was green synthesis, an ecological and sustainable method for obtaining nanomaterials using plant extracts as reducing agents or stabilizers. Thus, the chosen plants were Ginger rhizomes, Bay leaves, and Rose hips, in both fresh and dry form, due to the natural benefits they possess, and the Soxhlet method was used to obtain the plant extracts desired to be used in the synthesis. The composite dressings were developed in two distinct sample series, differentiated by the immersion time of BC in the precursor Zn2+ solution. The samples in the first series were obtained by precipitation in a mixture of Zn2+ solution and natural extract, whereas the samples in the second series were obtained by successive immersion in Zn2+ solution and then in natural extract, which demonstrated a considerable difference. The best antimicrobial activity tested against Gram-negative bacterium Escherichia coli was recorded for the composite material obtained in the presence of fresh rose hip extract, an aspect most likely related to the morphological and crystalline features of the ZnO phase, but also to the phytochemical profile of the extract used. Such eco-friendly materials represent valuable candidates for wound dressing applications due to their ability to support wound healing, relief burns, and skin irritation, provide antimicrobial protection, promote skin regeneration and reduce scarring, protect sensitive skin, and act as a barrier against external contaminants.
This cohort study compared split-thickness skin graft transplantation and dispersed implantation of autologous strip skin (ASS) grafts combined with small autologous columnar skin (SCS) grafts for the treatment of small-area deep burn wounds. The experimental group was treated with dispersed implantation of ASS grafts combined with SCS grafts, whereas the control group underwent split-thickness skin graft (STSG) transplantation. The graft survival rate was significantly greater in the experimental group (p < 0.0001). The time to complete epithelialization was similar for both groups (p = 0.6626). The ratio of the donor site area to the wound area was lower (p = 0.0002), and the healing time for the donor site was shorter in the experimental group (p < 0.0001). Additionally, the Vancouver Scar Scale (VSS) scores for both the donor and recipient sites were significantly lower in the experimental group (p < 0.0001, p = 0.0075). The combined implantation of ASS and SCS grafts effectively promoted the healing of small-area third-degree burn wounds, with good preservation of hair follicles and sebaceous glands. This method reduces wound contraction and damage to the donor site, with no significant lamellate scar hyperplasia observed during long-term follow-up, making it a viable alternative to split-thickness skin graft transplantation.
Burn wounds represent complex therapeutic challenges that conventional treatments often fail to address effectively, particularly regarding prolonged healing times, excessive scarring, and recurrent infections. Mesenchymal stromal cells (MSCs) have emerged as a promising therapeutic agent with unique regenerative capabilities specifically suited to burn wound repair through their multifaceted mechanisms, including regenerative, migratory, immunomodulatory, angiogenic, anti-fibrotic, and immunosuppressive potential. The therapeutic efficacy of MSCs is primarily mediated by their secretome, a complex mixture of bioactive factors, growth factors, and extracellular vesicles that orchestrate tissue repair processes. MSC-derived EVs have gained particular attention as cell-free therapeutic alternatives that deliver functional biomolecules while circumventing the limitations associated with direct cell transplantation. This review critically analyzes the specific and irreplaceable roles of MSCs and their derivatives in burn wound healing, focusing on their unique mechanisms of action, therapeutic advantages over conventional approaches, and the molecular pathways that distinguish them as essential therapeutic tools. We examine current evidence demonstrating their superior efficacy in promoting wound closure, reducing scar formation, and accelerating functional tissue regeneration, while identifying key research gaps and challenges that must be addressed for successful clinical translation.
Fibrotic scarring resulting from trauma, burns, or surgery affects over 100 million people annually and is associated with functional, aesthetic, and psychological burdens. Current treatments remain inadequate, highlighting the need for novel, effective, and cell-free therapeutic strategies. Extracellular vesicle-enriched preparations derived from human endometrial mesenchymal stem cells (eMSC-EV-enriched preparations) may possess regenerative and anti-fibrotic potential, yet their roles in scar modulation and underlying mechanisms remain unclear. eMSCs were isolated from human endometrial biopsies and characterized via flow cytometry and differentiation assays. The eMSC-EV-enriched preparations were obtained from conditioned medium and verified by TEM, NTA, and Western blotting. Functional assays were conducted in NIH3T3 fibroblasts to assess proliferation, migration, and transwell invasion capacity. A full-thickness cutaneous wound model and a bleomycin-induced dermal fibrosis model were used in C57BL/6 mice to evaluate tissue repair and fibrosis attenuation. Histological and molecular analyses were performed to assess collagen deposition, fibrosis-associated markers, and related signaling pathways. The potential involvement of miR-125b-5p in Smad2-related signaling was explored. The eMSC-EV-enriched preparations displayed characteristic vesicular morphology and marker expression. Compared with BMMSC-EV-enriched preparations, eMSC-EV-enriched preparations more effectively reduced fibroblast proliferation and migration, with decreased transwell invasion capacity in vitro. In vivo, the eMSC-EV-enriched preparations enhanced wound closure, reduced collagen deposition, and were associated with improved collagen organization and an increased number of appendage-like structures. Expression of α-SMA and collagen I and III was reduced in tissues treated with the eMSC-EV-enriched preparations. Furthermore, the preparations were associated with increased miR-125b-5p levels and decreased Smad2/p-Smad2 expression, suggesting involvement of the miR-125b-5p/Smad2 axis. In the bleomycin model, the eMSC-EV-enriched preparations attenuated dermal thickening and collagen accumulation during fibrosis induction. Our findings indicate that eMSC-EV-enriched preparations improve repair quality and attenuate fibrosis development, potentially through modulation of fibroblast activity and involvement of the miR-125b-5p/Smad2 signaling pathway. These findings support further investigation of eMSC-EV-enriched preparations as a cell-free strategy for improving tissue remodeling in fibrotic skin conditions.
Vitamin D plays an important role in immune regulation, collagen remodeling, and wound healing. In the general population, deficiency has been associated with poor wound repair and fibrosis, yet evidence in burn patients remains limited. Burn injuries often result in hypertrophic scarring and significant healthcare utilization for reconstructive and adjunctive procedures. This study examines the impact of preexisting vitamin D deficiency on hypertrophic scarring and scar-related healthcare utilization in a large, multi-institutional cohort of burn patients. The TriNetX Research Network was queried for patients ≥18 years old with burn injuries between 2010 and 2023. Patients with vitamin D deficiency, defined as 25-hydroxyvitamin D <20 ng/mL within 1 month before injury, were matched 1:1 to nondeficient controls using propensity score matching. Matching variables included demographics, BMI, comorbidities, substance use, vitamin deficiencies (A, C, E, and K), calcidiol levels, and total burn surface area. The primary outcome was hypertrophic scarring. Secondary outcomes included scar-related interventions: Z-plasty and intralesional corticosteroid injections. Cumulative incidence was assessed at 3, 12, and 24 months. Hazard ratios (HRs) with 95% CIs were calculated using Cox proportional hazards models. After matching, 6832 patients were included in each cohort. Vitamin D deficiency was associated with significantly higher rates of hypertrophic scarring at 3 months (5.82% vs 2.55%, HR 2.33, 95% CI, 1.93-2.81, P < .0001), 12 months (9.38% vs 4.56%, HR 2.12, 95% CI, 1.84-2.46, P < .0001), and 24 months (10.61% vs 5.26%, HR 2.09, 95% CI, 1.83-2.40, P < .0001). Vitamin D-deficient patients also demonstrated greater use of reconstructive procedures, including Z-plasty (HR 1.86-2.38) and corticosteroid injection (HR 3.14-3.56). Vitamin D deficiency is strongly associated with increased hypertrophic scarring and greater reliance on reconstructive and adjunctive procedures following burn injury. These results underscore the potential role of micronutrient status in long-term burn recovery. Prospective studies are needed to determine whether early detection and correction of deficiency can mitigate scarring and reduce healthcare utilization. For image description, please refer to the figure legend and surrounding text.