Secondary extremity lymphedema (SEL) is a chronic and progressive disorder resulting from impaired lymphatic drainage, most commonly following oncologic interventions such as breast or gynecological cancer surgery. Characterized by the accumulation of lymphatic fluid, progressive inflammation, adipose hypertrophy, and tissue fibrosis, SEL poses significant therapeutic challenges, particularly in its advanced stages. While conservative management remains the first-line treatment for mild cases, surgical intervention becomes essential in moderate to severe disease. Surgical approaches are generally categorized into physiological procedures, which aim to restore lymphatic continuity (e.g., lymphaticovenous anastomosis [LVA], vascularized lymph node transfer [VLNT]), and excisional techniques, which remove fibrotic and adipose tissue (e.g., liposuction, Charles procedure). Increasingly, integrated strategies combining physiological and excisional methods have demonstrated superior outcomes by targeting both fluid and solid components of the disease. However, multiple challenges remain, including the identification of functional lymphatic vessels, donor site morbidity, variability in long-term outcomes, and a lack of standardized surgical algorithms. Emerging evidence supports a component-based, individualized surgical framework tailored to disease severity, pathological tissue composition, and lymphatic functionality. Combined approaches such as the “3L” strategy (LVA, VLNT, and liposuction) have shown promise in enhancing volume reduction, minimizing infection risk, and improving quality of life. This review synthesizes recent advancements in SEL surgery and proposes a practical decision-making algorithm, the ISTL algorithm, which integrates clinical evaluations, imaging diagnostics, and surgical interventions for personalized treatment planning and improved long-term surgical outcomes.Clinical Trial RegistrationThis study was registered at the China Clinical Trial Registration (www.chictr.org.cn) with the registration number NCT06920732.

Background Keloid development following toe syndactyly division is a rare but troublesome condition, which can impose both esthetic and functional burden. Currently, there is no effective treatment for this condition. The present study proposed a new treatment for keloid after syndactyly division by 1470 nm laser and glucocorticoid injection (1470 LAGI). This study aimed to evaluate the efficacy of this treatment modality. Methods A retrospective study was conducted on 12 patients with 36 keloid cases, who underwent treatment with 1470 LAGI. VSS scores were applied for keloid evaluation (pigmentation, vascularity, pliability, and height). VAS was applied for assessing pain and itching, and the recovery rate was recorded. Results This study showed that the 1470 LAGI can improve the pathological status of keloids from toe syndactyly division (p < 0.001), with a recovery rate of 30.56%. Itching and pain also significantly improved (p < 0.001). Conclusion In terms of vascularity, pigmentation, pliability, and height, 1470 LAGI led to keloid regression after toe syndactyly division, with a recovery rate of 30.56%. Besides, the combined treatment significantly decreased the episodes of itching and pain, thereby improving the quality of life. Therefore, it is an effective minimally invasive treatment for keloid following toe syndactyly division in children.

Background:Noxious lifestyle factors including spicy diets and hot baths may lead to scar formation and recurrence. These phenomena are related to the activation of the transient receptor potential vanilloid-1 (TRPV1) cation channel. Our previous study revealed significant upregulation of TRPV1 expression in the dermis of hypertrophic scar (HS), while the exact underlying mechanism of TRPV1 activation in HS remains ill-defined. This study aims to clarify the contribution of TRPV1 activation to HS pathogenesis, particularly in relation to aberrant angiogenesis. Methods:First, this study employs single-cell RNA sequencing technology to analyze the association between vascular endothelial cells and the development of HS. Complementarily, bioinformatics analysis combined with histological validation is utilized to investigate the relationship between TRPV1 channels and aberrant angiogenesis within HS formation. Furthermore, the correlation between TRPV1 activation and HS phenotypes is rigorously validated at the in vivo level. In parallel, in vitro experiments are conducted to elucidate the impact of TRPV1 channel activation on the biological behaviors and functions of vascular endothelial cells. Subsequently, key downstream signaling pathways of TRPV1 are screened, and their molecular mechanisms in regulating vascular endothelial cell-mediated angiogenesis are systematically verified. Finally, a comprehensive analysis is performed to establish the clinical relevance of the TRPV1/nuclear factor kappa-B (NF-κB)/interleukin-6 (IL-6) axis with vascularization severity and adverse prognostic outcomes in hypertrophic scarring. Results:Single-cell RNA sequencing revealed significant cellular heterogeneity in vascular endothelial cells between normal skin and HS, indicating activated angiogenesis and substantial vascular endothelial cell alterations during HS development. Bulk RNA-seq and clinical analyses further confirmed this angiogenesis activation, demonstrating a close association with TRPV1 channel activation. In vivo studies established that capsaicin (CAP)-induced TRPV1 activation exacerbated HS progression through enhanced angiogenesis, whereas TRPV1 ablation or local inhibition markedly attenuated this effect. In vitro experiments demonstrated that TRPV1 activation regulated angiogenesis by promoting pro-angiogenic phenotypes. Transcriptomic analysis and functional validation identified the IL-6/signal transducer and activator of transcription 3 pathway as a downstream NF-κB-dependent pro-angiogenic axis mediated by TRPV1 in HS vascular endothelial cells. Critically, dermal overexpression of the TRPV1/NF-κB/IL-6 axis in HS patients correlated strongly with both disease severity and recurrence. Conclusions:Here, we show that the development of HS is strongly correlated with endothelial angiogenic activity. TRPV1 activation by CAP enhances proangiogenic processes including endothelial proliferation, migration, and tubule formation, while reducing apoptosis through the TRPV1/NF-κB/IL-6 axis. In a rabbit ear HS model, stimulation of TRPV1 contributes to the formation of HS via the TRPV1/NF-κB/IL-6 axis, whereas pharmacological ablation of TRPV1 significantly reversed these phenotypes. These findings shed light on the underlying molecular mechanisms and provide a potential therapeutic target for HS.

Pulse dye laser (PDL) and intense pulse light (IPL) have been applied in the early scar treatment to alleviate erythema, but no comparative analysis has been conducted to evaluate the performance of the two. This is a retrospective comparative study to assess whether PDL and IPL had the same efficacy in the early intervention of surgical linear scars. We conducted a retrospective study on linear surgical scars which received two consecutive monthly sessions of PDL (n = 50) or IPL (n = 68) from January 2017 to December 2023. All interventions were initiated two weeks after the suture removal. Vancouver Scar Scale (VSS), the incidence of hypertrophic scars and Global Aesthetic Improvement Scale (GAIS) were measured at baseline and one month after the last treatment. Subgroup analysis was further performed on scars located in the face, neck and trunk. There was no significant difference in the downregulation rate of VSS between PDL (36.6 www.springer.com/00266 .

Fluorescence imaging-based combined photodynamic (PDT) and photothermal (PTT) therapy strategies have presented as an attractive technique for cancer diagnosis and treatment, offering advantages such as noninvasiveness, real-time monitoring and high antitumor efficiency. However, conventional synergistic PDT/PTT platforms often rely on complex multicomponent nanosystems, which face challenges such as batch-to-batch variability, inefficient energy transfer, and the need for multiple excitation sources. To overcome these limitations and achieve a streamlined yet multifunctional system, we rationally designed and synthesized a donor-acceptor conjugated polymer CPBTT, and further developed conjugated polymer nanoparticles CPBTT-NPs. Upon irradiation with a single 808 nm laser, the CPBTT-NPs exhibited a remarkable multifunctional response: (1) strong NIR-II fluorescence for high-resolution imaging of deep tissues; (2) generating cytotoxic reactive oxygen species (via type-I PDT pathway); (3) generating substantial localized heat for PTT. In vitro and in vivo experiments demonstrate that CPBTT-NPs effectively achieve deep-tissue tumor visualization, precise tumor accumulation and potent tumor ablation with minimal systemic toxicity. This all-in-one phototherapeutic platform thus provides a simple, reproducible, and efficient strategy for advanced imaging-guided cancer theranostics.

While mesenchymal stem cells (MSCs) and extracellular vesicles (EVs) hold therapeutic potential, their clinical translation is hindered by suboptimal delivery systems. This study presents a directly translatable strategy for treating intrauterine adhesions (IUA) using a clinical-grade, injectable fibrin hydrogel (Porcine Fibrin Sealant, PFS) to deliver MSCs/EVs. This platform not only ensures biocompatibility and surgical handling but also provides a protective niche. In rat models of mechanically- and ethanol-induced IUA, optimal-dose PFS-MSCs injected into the uterine cavity promote endometrial regeneration, as shown by increased endometrial thickness, gland number, and reduced fibrosis. This treatment further restores reproductive function, as evidenced by the enhanced secretion of fertility-related factors, improved embryo implantation, and the live birth of healthy offspring. Mechanistically, transcriptomic and histological analyses of the PFS-MSCs treated group revealed dual repair mechanisms: (1) immune remodeling, characterized by decreased M1 macrophages, enhanced M2 macrophage polarization, expanded Treg populations, and upregulated IL-4 level, and (2) tissue regeneration, marked by upregulated bFGF level, increased angiogenesis, and enhanced cell proliferation. Crucially, the cell-free PFS-EVs strategy achieved therapeutic equivalence to the PFS-MSCs strategy, fully reversing ethanol-induced IUA damage and enabling fertility recovery. This safe and effective platform presents a directly translatable strategy for IUA treatment.

Hypertrophic scars are prevalent fibrotic disorders that arise following skin wound healing, often resulting in both functional impairments and significant cosmetic concerns for affected individuals. Current therapeutic options, with pressure therapy being standard, frequently encounter challenges related to patient compliance and inconsistent efficacy. Given these limitations, there is a compelling need for innovative approaches to improve scar management in clinical settings. This study aimed to systematically evaluate the safety and therapeutic efficacy of a novel pressure-enhanced scar patch designed to address the aforementioned clinical challenges. A rabbit ear hypertrophic scar model was utilized, established through the perichondrium-preservation method, which demonstrated a 100

Articular cartilage repair remains a major clinical challenge. Although microfracture (MF) is widely applied, it frequently results in fibrocartilaginous repair with limited mechanical durability and unsatisfactory long-term outcomes. The persistent inflammatory microenvironment following cartilage injury disrupts tissue homeostasis and impairs chondrogenic differentiation of bone marrow stem cells (BMSCs), representing a major impediment to regeneration. Here, an injectable, thermosensitive composite hydrogel, constructed from a dopamine-modified hyaluronic acid and Pluronic F127 network, which incorporates chlorogenic acid (CA) and ZIF-8 nanoparticles encapsulated with kartogenin (KGN), is developed to establish a cascade repair strategy. Preferential release of CA can efficiently reprogram macrophages toward a pro-regenerative M2 phenotype and improve anti-inflammatory cytokine secretion, thereby creating a pro-regeneration microenvironment. Subsequently, the sustained release of KGN further stimulates BMSCs chondrogenic differentiation within this optimized niche. Biological assays demonstrate that this synergistic mechanism enhances cartilage-specific matrix synthesis and alleviates matrix degradation under inflammatory conditions. Furthermore, this composite hydrogel, combined with MF, improves cartilage tissue regeneration in a rat model, as evidenced by smooth defect filling, well-organized extracellular matrix deposition, and reduced Matrix metalloproteinase 13-mediated degradation. This work presents a synergistic immuno-chondroregenerative platform that overcomes fundamental limitations of MF and offers a promising paradigm for functional cartilage regeneration.

The lymphatic system serves many more functions than simply maintaining tissue fluid homeostasis, and its structural and functional changes indicate the occurrence of disease. Current clinical methods for the assessment of the lymphatic system, however, are severely limited because of their nontargeting ability, invasiveness, high cost, and radiation risk. Herein, we propose a simple and painless method for visualizing and quantifying the lymphatic system. This method is based on the noninvasive administration of a novel lymphatic tracer via dissolvable microneedles, followed by the application of a portable detection device for near-infrared (NIR) imaging. The tracer is prepared by incorporating the clinically approved NIR fluorescent dye methylene blue (ME) into the nanomaterial monomethoxyl poly(ethylene glycol)-b-poly(ε-caprolactone) (MPEG-PCL@ME). This novel tracer displays superior fluorescence properties, stability, biocompatibility, and targeting features in comparison with ME solution alone. Lymphography with MPEG-PCL@ME in vivo clearly revealed the lymphatic vessel morphology. Notably, compared with ME and indocyanine green, MPEG-PCL@ME can easily identify the dominant lymphatic vessels and nodes in rats with higher imaging quality. Furthermore, a series of segmental contracting sections are detected with MPEG-PCL@ME, allowing straightforward identification of the lymphatic pump, which provides direct evidence for exquisitely evaluating lymphatic functions.

Epidermal growth factor receptor (EGFR) inhibitors frequently cause cutaneous toxicities that impair patients' quality of life and may compromise treatment adherence. Although topical vitamin K1 (VK1) has shown therapeutic potential, its clinical efficacy remains inconsistent, largely due to poor distribution within pharmacologically relevant skin compartments, particularly the viable epidermis and pilosebaceous units. To address this, we developed a VK1-loaded liposome‑in‑hydrogel (VK1-Lipo-Gel) capable of sustaining intradermal drug residence while minimizing systemic exposure. Compared with the commercial VK1 cream, VK1-Lipo-Gel markedly prolonged VK1 retention in the skin. VK1 remained detectable in the viable epidermis-dermis (VED) for up to 36 h, yielding a Cmax of 1.64 ± 0.10 μg/cm2 at 8 h and an AUC0-36h of 33.16 ± 1.70 μg·h/cm2. Notably, the formulation promoted preferential localization within the VED and pilosebaceous units, with plasma VK1 levels below the LLOQ. More importantly, VK1‑Lipo‑Gel did not compromise the antitumor efficacy of erlotinib. In an erlotinib-induced skin toxicity model, by restoring EGFR-ERK signaling, VK1-Lipo-Gel more effectively reinforced epidermal barrier function, attenuated inflammatory responses, and ameliorated follicle‑associated alterations. These results demonstrate that optimizing intradermal retention and compartment‑specific distribution, rather than simply increasing transdermal flux, is a superior strategy for managing EGFR inhibitor-induced cutaneous toxicity, and support the translational potential of liposome‑hydrogel hybrids for topical drug delivery.

Hypertrophic scars, characterized by excessive fibroblast activation, present significant clinical challenges. Current treatments (e.g., laser, surgery, steroids) face limitations: Surgery is costly and associated with high recurrence rates, while pharmacological interventions often induce pain and exhibit low bioavailability or efficacy. To address this, we engineered a novel chiral supramolecular biomaterial derived from L-/D-phenylalanine and D-phenylalanine (L/DP) with well-defined nanostructure and optical activity. L/DP achieved biomimetic integration and stereoselective regulating of integrin β1 (ITGβ1) in scar tissue. In vitro, LP suppressed fibroblast proliferation by downregulating ITGβ1 (72

Hypertrophic scarring (HTS) represents a common clinical challenge characterized by excessive fibroblast activation and tissue fibrosis. However, the upstream signals driving pathological fibroblast proliferation remain poorly understood. Here, we identify the G protein-coupled receptor MrgprX2 (human)/MrgprB2 (mouse), traditionally restricted to mast cells, as an inducible pro-fibrotic receptor in dermal fibroblasts during HTS progression. MrgprX2 is markedly upregulated in dermal fibroblasts from HTS, and pharmacological inhibition of MrgprX2 significantly reduces fibrosis in humanized skin organoid models. In mouse studies, the endogenous peptide LL37 emerged as an MrgprX2/B2 activator in fibroblasts, triggering calcium influx, transforming growth factor β1 (TGF-β1) secretion, and proliferation. Genetic ablation of MrgprB2 in fibroblasts significantly reduced fibrosis in vivo, establishing the LL37-MrgprX2/B2-TGF-β1 axis as a key mediator of fibroblast activation and fibrotic remodeling. Together, our findings position MrgprX2/B2 as a critical molecular link between tissue injury-associated signals and fibrotic pathology, offering a promising therapeutic target for fibroblast-driven fibrosis in HTS.

Noxious lifestyle factors including spicy diets and hot baths may lead to scar formation and recurrence. These phenomena are related to the activation of the transient receptor potential vanilloid (TRPV1) cation channel. Our previous study revealed significant upregulation of TRPV1 expression in the dermis of hypertrophic scar (HS), while the exact underlying mechanism of TRPV1 activation in HS remains ill-defined. Firstly, this study employs single-cell RNA sequencing technology to analyze the association between vascular endothelial cells and the development of HS. Complementarily, bioinformatics analysis combined with histological validation is utilized to investigate the relationship between TRPV1 channels and aberrant angiogenesis within HS formation. Furthermore, the correlation between TRPV1 activation and HS phenotypes is rigorously validated at the in vivo level. In parallel, in vitro experiments are conducted to elucidate the impact of TRPV1 channel activation on the biological behaviors and functions of vascular endothelial cells. Subsequently, key downstream signaling pathways of TRPV1 are screened, and their molecular mechanisms in regulating vascular endothelial cell-mediated angiogenesis are systematically verified. Finally, a comprehensive analysis is performed to establish the clinical relevance of the TRPV1/nuclear factor kappa-B (NF-κB)/interleukin-6 (IL-6) axis with vascularization severity and adverse prognostic outcomes in hypertrophic scarring. Single-cell RNA sequencing revealed significant cellular heterogeneity in vascular endothelial cells between normal skin (NS) and HS, indicating activated angiogenesis and substantial vascular endothelial cell alterations during HS development. Bulk RNA-seq and clinical analyses further confirmed this angiogenesis activation, demonstrating a close association with TRPV1 channel activation. In vivo studies established that capsaicin (CAP)-induced TRPV1 activation exacerbated HS progression through enhanced angiogenesis, whereas TRPV1 ablation or local inhibition markedly attenuated this effect. In vitro experiments demonstrated TRPV1 activation regulated angiogenesis by promoting pro-angiogenic phenotypes. Transcriptomic analysis and functional validation identified the IL-6/Signal Transducer and Activator of Transcription 3 (STAT3) pathway as a downstream NF-κB-dependent pro-angiogenic axis mediated by TRPV1 in HS vascular endothelial cells. Critically, dermal overexpression of the TRPV1/NF-κB/IL-6 axis in HS patients correlated strongly with both disease severity and recurrence. Here, we show that the development of HS is strongly correlated with endothelial angiogenic activity. TRPV1 activation by CAP enhances proangiogenic processes including endothelial proliferation, migration and tubule formation, while reducing apoptosis through the TRPV1/ NF-κB/ IL-6 axis. In a rabbit ear HS model, stimulation of TRPV1 contributes to the formation of HS via the TRPV1/NF-κB/IL-6 axis, whereas pharmacological ablation of TRPV1 significantly reversed these phenotypes. These findings shed light on the underlying molecular mechanisms and provide a potential therapeutic target for HS.

Pathological scars (PSs), which encompass hypertrophic scars (HSs and keloids, pose significant challenges in the realm of plastic surgery due to their characteristics of excessive fibrosis and persistent pruritus. This fibrosis can lead to both functional limitations and aesthetic issues, while pruritus often indicates ongoing scar development and greatly impacts quality of life. Although the underlying cause of both conditions is linked to dysregulated inflammation, the specific connections between fibrosis and pruritus are not well understood. Transient receptor potential channels (TRP), known for their roles in systemic fibrotic diseases and as mediators of chronic pruritus in skin disorders, may play a crucial role in the environment of pathological scars. This review compiles existing research to investigate the idea that certain TRP subfamilies (TRPA1, TRPV1, TRPV3, TRPV4) could link fibrosis and pruritus in pathological scars by interacting with common inflammatory mediators. We suggest that these channels might act as central molecular hubs that connect the signaling pathways of fibrosis and pruritus in these scars. Therefore, targeting TRP channels pharmacologically could be a promising approach to simultaneously alleviate both fibrosis and pruritus, potentially leading to a new dual-pathway treatment strategy for managing pathological scars. Our review also critically examines the current landscape of TRP-targeted therapies, pointing out challenges such as limited selectivity for specific subtypes and the lack of clinical trials focused on pathological scars, while emphasizing the necessity for interdisciplinary advancements in this area. In conclusion, while TRP channels are attractive targets for therapeutic intervention in pathological scars, their effective clinical application necessitates a more profound understanding of the mechanisms specific to scars and the creation of targeted delivery methods.

Background:Extensive postburn facial scarring cannot achieve aesthetic resurfacing with skin graft or mismatched flaps. Although adjacent flap donor sites, such as the neck or deltopectoral area, provide ideal skin characteristics, flap transfer may be highly limited due to the absence of proper axial vessels. Here, we demonstrate an innovative reconstructive alternative in terms of prefabrication and tissue expansion for extensive facial resurfacing. Methods:A serratus anterior fascia flap within the serratus branch of the thoracodorsal artery was harvested and microsurgically transferred as the pedicle of a prefabricated cervicothoracic flap. The flap, with the fascia located in a subcutaneous pocket over a tissue expander, was raised, islanded, and rotated to reconstruct the facial defect after reliable expansion and maturation. Flap size, donor/recipient site, surgical outcomes, and donor-site morbidity were all evaluated. Results:The flap sizes ranged from 13 × 10 to 27 × 21 cm. All 15 patients with extensive postburn facial scars, aged 15-40 years (mean 30.73 y), achieved successful reconstruction without major complications after 6-12 months of follow-up. Conclusions:The prefabricated, expanded cervicothoracic flap with the serratus branch of the thoracodorsal artery demonstrated a favorable color and texture match with the recipient site. The donor site can be primarily closed with minimized aesthetic and functional compromise.

Conventional periodontitis therapies are limited by their inability to concurrently address the interconnected challenges of persistent bacterial infection, excessive oxidative stress, and immune dysregulation. To overcome this, we developed an injectable, pH-responsive nanocomposite polypeptide hydrogel, PepGel@ZnO-PLP, through rational molecular interface engineering. The system is constructed by integrating poly-L-proline (PLP)-functionalized zinc oxide nanoparticles (ZnO-PLP) into a poly-L-glutamate containing polypeptide network (PepGel) via dynamic Zn2+-carboxylate coordination. This critical PLP interface ensures colloidal stability of ZnO nanoparticles and enables the formation of a homogeneous, pH-responsive release network. In the acidic periodontal microenvironment, the hydrogel exhibits potent antibacterial and reactive oxygen species (ROS)-scavenging activities. Furthermore, via PLP-enabled interfacial engineering, PepGel@ZnO-PLP reprograms inflammatory macrophage immunometabolism by driving a glycolytic-suppressed metabolic state that establishes metabolic homeostasis toward a reparative M2 phenotype, a process in which the PI3K-Akt pathway may be involved. In a murine periodontitis model, PepGel@ZnO-PLP adheres to periodontal defects, effectively disrupting the infection-inflammation cycle and leading to significant alveolar bone preservation. This work underscores the power of precise molecular-level design for holistically reprogramming the pathological microenvironment and offers a novel nanocomposite hydrogel for ameliorating inflammatory periodontal bone loss.

BackgroundPulsed dye lasers (PDLs) and intense pulsed light (IPL) are commonly used for treating cutaneous vascular diseases but lack standardized and reproducible treatment protocols. Reliable vascular models are needed to visually assess posttreatment responses.MethodsSixteen male rabbits were divided into two groups, with each ear subdivided into three treatment regions. PDL treatment was applied with pulse durations of 0.45 ms (fluences: 4, 5.5, and 8 J/cm2) and 1.5 ms (fluences: 5.5, 8, and 13 J/cm2). IPL was applied in single-pulse (10, 13, and 15 J/cm2) and double-pulse (10, 13, 17, and 20 J/cm2) modes. Vascular morphology and blood flow were evaluated using photographs and laser speckle contrast imaging (LSCI) before treatment, immediately after treatment, on days 1, 3, 5, 7, and 14. Histopathological analysis was performed 24 hours posttreatment. Statistical analysis was conducted with two-way ANOVA and Tukey's test, with P < 0.05 considered to indicate statistical significance.ResultsThe dorsal ear vessels of rabbits consisted of longitudinally arranged main blood vessels (MBVs) and fan-shaped branch blood vessels (BBVs), with diameters ranging from 150–300 μm and 90–120 μm, respectively. In the PDL treatment, effective vessel closure with limited peripheral tissue damage was achieved using 0.45 ms at 5.5 J/cm2 for BBVs, whereas 1.5 ms at 8.0 J/cm2 was associated with qualitative evidence of more sustained MBV closure. In the IPL treatment, a single pulse at 13.0 J/cm2 effectively closed the branch vessels, whereas the double-pulse mode primarily induced vessel dilation.ConclusionThe rabbit ear vascular model, combined with dermoscopy, LSCI, and histopathology, provides a reproducible multimodal platform for longitudinal evaluation and systematic parameter screening, offering a reliable preclinical foundation for comparative assessment and protocol refinement prior to clinical translation.

Chronic skin wounds remain a clinical challenge due to impaired extracellular matrix (ECM) reconstruction and dysregulated immune responses. Biomaterials that simultaneously support matrix formation and modulate the wound immune microenvironment are, therefore, highly desirable. Here, we developed a mesoporous bioactive glass-recombinant collagen III nanocomposite capsule (Cap-ReCol III), in which recombinant collagen III is adsorbed onto mesoporous bioactive glass nanoparticles to form an integrated organic-inorganic unit. Cap-ReCol III exhibited a well-defined mesoporous structure and favorable physicochemical properties. In vitro, it showed excellent cytocompatibility and significantly enhanced fibroblast proliferation, migration and contractility, accompanied by increased expression of α-smooth muscle actin and collagen-related markers. In a full-thickness mouse wound model, Cap-ReCol III accelerated wound closure and promoted granulation tissue formation and collagen deposition. Importantly, Cap-ReCol III modulated the immune microenvironment by reducing neutrophil accumulation and granzyme B+ CD8+ T cells, while increasing regulatory T cells and IL-13+ CD8+ T-cell subsets associated with tissue repair. Adoptive transfer experiments in Rag2-/- mice further confirmed the essential role of adaptive immunity in this process. Overall, Cap-ReCol III promotes wound healing by coordinating ECM remodeling and adaptive immune modulation, providing a promising strategy for skin regeneration.

Deep dermal burns are common injuries characterized by prolonged healing time. The wound healing process involves inflammatory, proliferative, and remodeling phases regulated by growth factors, including FGF2 and EGF, which play roles in angiogenesis, fibroblast proliferation, re-epithelialization, and tissue repair. UC-MSC secretome contains cytokines and growth factors that may enhance wound healing. This pilot study aims to evaluate the effect of topical UC-MSC secretome on serum FGF2 and EGF levels and wound healing in deep dermal burns in Wistar rats. This study used a post-test control group design in Wistar rats with deep dermal burns. Animals were divided into secretome-treated, vaseline-treated, and untreated groups, with evaluations on days 3 and 14. Serum FGF2 and EGF levels were measured using ELISA, while wound healing was assessed through wound width analysis and histopathology. Trends in serum FGF2 and EGF levels increased in all groups, with the secretome-treated group showing higer mean levels. Histopathology demonstrated better epidermal and dermal regeneration and higher healing scores in the secretome group. Clinical assessment also showed greater reduction in wound width. Topical UC-MSC secretome was possibly associated with increased serum FGF2 and EGF levels and improved wound healing in deep dermal burns in Wistar rats. Level of Evidence: not ratable.