Search Results (1,151)

The skin microbiome plays a central role in maintaining cutaneous homeostasis, and its disruption has been implicated in a wide range of inflammatory and degenerative skin disorders. This review critically evaluates the current evidence on topical probiotics in dermatology, integrating microbiological mechanisms, formulation strategies, and translational and regulatory challenges within a single framework—an angle that remains insufficiently addressed in previous reviews. A targeted search of PubMed and ScienceDirect (2009–2025) was conducted to identify relevant original studies. The results suggest that topical probiotics may promote skin health through three broad, interconnected axes: (i) modulation of host responses (e.g., inflammation, immune signaling, and oxidative stress); (ii) microbial ecology and pathogen control (e.g., competition, acidification, and antimicrobial metabolite production); and (iii) support of barrier function and tissue repair (e.g., lipid metabolism, re-epithelialization, and extracellular matrix remodeling). Efficacy appears to depend strongly on strain specificity, formulation design, and microbial viability during storage and application. In addition to conventional dosage forms, advanced platforms—hydrogels, microgels, microparticles, and microneedle-based systems—have been investigated to improve stability and local delivery. Promising preclinical and clinical results have been reported for acne, wound healing, skin barrier repair, and anti-aging applications. Nevertheless, major translational challenges remain, including limited standardization, instability of live microorganisms, insufficiently representative experimental models, and regulatory uncertainty. Overall, topical probiotics represent a promising microbiome-based strategy in dermatology, but robust clinical validation and formulation optimization are still needed to support broader clinical implementation. Full article

(-)-Epigallocatechin gallate (EGCG) possesses potent bioactivities but its applications in functional cosmetics is severely limited by its poor water solubility and chemical instability. To overcome these challenges, this study engineered a recombinant levansucrase from Vibrio natriegens to catalyze the transfructosylation of EGCG. The conversion rate of EGCG to fructoside reached 65.59%. The purified product was unequivocally identified as EGCG-1F, with a fructosyl group linked to the 3′-hydroxyl group. Compared to pristine EGCG, EGCG-1F exhibited remarkably enhanced water solubility (96.6-fold that of EGCG) and aqueous stability under acidic and thermal conditions. Biological evaluation revealed that EGCG-1F significantly enhanced HaCaT cell migration, upregulated the expression of basement membrane-associated collagens in ultraviolet B-damaged HaCaT cells, and modulated ultraviolet A-induced senescence in human dermal fibroblasts by type I collagen, type III collagen and matrix metalloproteinase-1 balance. This study demonstrates that enzymatic fructosylation is an effective approach to generate a stable and safe EGCG derivative with potential applications in skin barrier repair and anti-aging functional cosmetics. Full article

Bone healing is a complex regenerative process regulated by interactions between skeletal and host biologic responses, and failure of bone repair remains a major challenge in orthopedic surgery. Using a murine model, this study investigated whether a preemptive priming stimulus could enhance healing of a subsequent contralateral cortical bone defect and whether the type and timing of the stimulus influenced this response. Skeletally mature male mice were randomized into six groups (n = 6/group) receiving either no stimulus, a skin incision, skin and muscle incisions, or a unicortical femoral drill hole stimulus. A subcritical-sized 1 mm × 2 mm unicortical defect was subsequently created in the contralateral femur after intervals of 2, 6, or 12 weeks, depending on group allocation. Femora were harvested 8 weeks later for micro-computed tomography, histology, and immunofluorescence analyses. Mice undergoing muscle elevation 2 weeks prior to defect creation and mice receiving drill hole stimulus 12 weeks prior demonstrated the greatest degree of cortical regeneration and healing of the contralateral subcritical-sized defect, with normalized cortical thicknesses reaching 104% and 109% of adjacent native cortex, respectively. Histologic analysis confirmed restoration of mature cortical architecture in these groups. Immunofluorescence analysis demonstrated a relative shift toward an Arg1-associated reparative macrophage profile with reduced iNOS-associated inflammatory signaling, suggesting that modulation of the innate immune response contributed to the enhanced regenerative healing observed. These findings demonstrate that priming stimuli can enhance subsequent bone healing in a timing- and stimulus-dependent manner and may represent a novel strategy to optimize bone regeneration. Full article

Stem cells, with their self-renewal and multi-lineage differentiation potential, hold promise for tissue repair and intractable diseases treatment. Yet clinical translation of stem cell therapies has long been hindered by insufficient scalable stem cell manufacturing, stemness loss and functional decline in 2D expansion, and poor post-transplantation cell retention, unregulated fate control. Programmable microcarriers (MCs) paired with 3D dynamic culture offer an emerging strategy to address these bottlenecks and enable stem cell fate regulation. In this review, we systematically review advanced MC fabrication strategies for stem cell fate regulation, comparing features of emerging technologies (microfluidics, electrospraying, in-air microfluidics, integrated in situ functionalization) and their implications for programmable MC control and scalable manufacturing. We analyze how MCs modulate stem cell behaviors (adhesion, proliferation, stemness maintenance, differentiation) via synergistic static physicochemical cues and dynamic stimuli-responsive properties. We map the latest advances in functionalized MC-mediated stem cell therapy across osteochondral defects, autoimmune, skin, ophthalmic and neurodegenerative diseases. Finally, we pinpoint unresolved challenges for clinical translation of MC–stem cell system and outline key future research directions. This review offers a systematic roadmap for advancing programmable MC fabrication, clinical-grade stem cell biomanufacturing, and precise cell therapy development. Full article

Burn wound healing is a complex and dynamic process involving coordinated regulation of inflammation, oxidative stress, angiogenesis, and tissue remodeling. Polygonum cuspidatum, a traditional Chinese medicinal herb widely used for trauma- and inflammation-related disorders, represents an important source of bioactive compounds for tissue repair. Piceatannol (PIC), a naturally occurring stilbene constituent of P. cuspidatum, possesses potent anti-inflammatory and antioxidant activities; however, its therapeutic potential in burn wound healing remains insufficiently understood. In the present study, the therapeutic effects and underlying mechanisms of topical PIC were investigated using a murine deep second-degree burn model combined with multiple skin-related cellular models, including keratinocytes, fibroblasts, endothelial cells, and macrophages. PIC markedly accelerated wound closure and improved histological architecture, as evidenced by reduced inflammatory infiltration, enhanced collagen organization, and increased neovascularization. Mechanistically, PIC suppressed NF-κB activation and modulated KEAP1/NRF2-associated redox signaling, thereby alleviating inflammation–oxidative stress crosstalk during wound healing. In keratinocyte–fibroblast co-culture systems, PIC inhibited fibroblast-to-myofibroblast transition, reduced α-smooth muscle actin (α-SMA) expression, and attenuated excessive collagen deposition, suggesting anti-fibrotic activity. In addition, PIC promoted endothelial tube formation through activation of the STAT3–VEGF signaling axis. Collectively, these findings demonstrate that PIC facilitates burn wound repair through coordinated anti-inflammatory, antioxidative, pro-angiogenic, and anti-fibrotic effects. This study provides pharmacological support for the therapeutic potential of P. cuspidatum-derived compounds in burn management and highlights PIC as a promising candidate for topical treatment of burn injuries. Full article

Introduction: Fish skin is the first line of defense against the aquatic environment, acting as a physical, chemical, and immunological barrier. In addition to preventing pathogen entry, the skin and its mucus contribute to osmoregulation, innate immunity, and redox balance. Skin lesions—caused by mechanical damage, parasites, environmental stress, or handling—disrupt this barrier, increasing susceptibility to infections, inflammation, and production losses. Thus, efficient skin regeneration is essential for fish welfare and performance. Nutrition plays a key role in this process by providing substrates for epithelial repair, immune function, and antioxidant defense. Among dietary factors, zinc (Zn) is particularly important due to its involvement in cell proliferation, enzymatic activity, and maintenance of skin integrity. Objective: Our objective is to assess the effectiveness of image-based analysis in quantifying the skin healing process in Atlantic salmon fed diets supplemented with zinc. Methodology: The trial comprised three dietary treatments: a control diet with 42 mg Zn per kg (D1), and two diets supplemented up to 120 mg/kg of zinc, derived from inorganic (D2) or organic (D3) forms. Pit-tagged fish with an initial body weight (78 ± 0.1 g) were fed the diets for 75 days. After 15 days of experimental feeding, a standardized wound lesion (2.5 mm diameter × 0.5 mm depth) was inflicted in deeply anesthetized fish, with a disposable biopsy punch, in the dorsal area. After wound infliction, the fish resumed their normal feeding regime for the rest of the trial days. The progression of skin wound healing was assessed using standardized digital image analysis. High-resolution photographs of individual wounds were collected 8, 16, 24 and 32 days post-wounding. All images were acquired under standardized conditions with the inclusion of ArUco identifiers to enable a subsequent computer-assisted comparison. Morphometric parameters (wound width, diameter, perimeter and area) were used to assess wound contraction and closure over time. In parallel, a semi-quantitative visual scoring system was applied to each wound image to capture qualitative aspects of healing that are not fully described by morphometric data alone. Results: Full data analysis is currently underway, but the first results show beneficial effects of dietary zinc supplementation on the skin regenerative process. Conclusions: The combined use of objective digital measurements and standardized visual scoring enabled a comprehensive evaluation of wound healing progress, bridging quantitative tissue remodeling with biologically relevant phenotypic outcomes. This image-based framework provides a sensitive and reproducible approach for assessing dietary interventions targeting skin regeneration and barrier restoration in Atlantic salmon. Full article

Background and Clinical Significance: Peristomal pyoderma gangrenosum (PPG) is a rare subtype of pyoderma gangrenosum, most commonly associated with inflammatory bowel disease or haematologic disorders. Its occurrence in patients with solid malignancies is uncommon. PPG in an oncologic setting poses diagnostic and therapeutic challenges because systemic immunosuppressive therapy, wound care, and ongoing chemotherapy must be carefully balanced; Case Presentation: We report the case of a Japanese man in his 50s with stage IVB rectal adenocarcinoma who developed rapidly progressive peristomal ulceration clinically consistent with PPG around a colostomy 12 weeks after initiation of panitumumab-containing systemic chemotherapy. The diagnosis was made on clinical grounds and was strongly supported by the clinical morphology, exclusion of major mimickers, and response to systemic corticosteroid therapy, although histopathological confirmation was not obtained. Because existing diagnostic criteria for pyoderma gangrenosum are not specifically designed for peristomal disease, they were used as supportive rather than definitive diagnostic tools. Skin biopsy was avoided due to the risk of pathergy at the peristomal site. Superficial cultures were not obtained because frequent cleansing and faecal contamination were likely to compromise diagnostic accuracy. To minimise mechanical pathergy, the stoma appliance was changed from a one-piece soft convex system to a two-piece flat system. Multidisciplinary management, including systemic corticosteroids, meticulous stoma care, and selective ultrasonic debridement, resulted in complete epithelialisation by Week 26. Chemotherapy was temporarily withheld during the active inflammatory phase and later resumed. Despite successful control of the peristomal ulceration, the patient died from progressive malignancy at Week 34; Conclusions: This case highlights the clinical challenge of balancing immunosuppressive therapy for clinically suspected PPG with ongoing oncologic treatment. Mechanical pathergy related to stoma appliance use was considered a more likely precipitating factor than chemotherapy alone, although panitumumab may have contributed to impaired cutaneous repair. Close collaboration among dermatologists, oncologists, surgeons, WOC nurses, and family caregivers is essential for multidisciplinary decision-making in complex oncologic settings. Full article

Objectives: Skin wound repair has long remained a crucial clinical challenge, in response to which, in this study, we propose a novel injectable hydrogel delivery system. In particular, we focus on the efficient delivery of bioactive factors and modulation of the local wound microenvironment. Methods: The hydrogel integrates selenium nanoparticles (SeNPs) and basic fibroblast growth factor (bFGF), which serve as key therapeutic components in the proposed system, and are additionally co-integrated with oxidized hyaluronic acid (OHA) and heparin-grafted carboxymethyl chitosan (CMCS-g-Hep) to construct a multifunctional SeNPs/bFGF-loaded CMCS-g-Hep/OHA hydrogel network. Accordingly, this proposed hydrogel was systematically evaluated using chemical synthesis, physicochemical characterization, in vitro cellular assays, and C57BL6J mice studies, which we used to jointly assess the biocompatibility and wound-healing efficacy of the proposed system. Results: The results demonstrated that the hydrogel enabled sustained bFGF release and was capable of significantly enhancing fibroblast proliferation, migration, and collagen deposition. In a mouse skin defect model, treatment with the loaded hydrogel markedly accelerated wound closure. Additionally, we conducted mechanistic investigations to further illustrate that the hydrogel can modulate the wound microenvironment by regulating inflammatory and chemotactic signaling pathways. Conclusions: These findings suggest a promising therapeutic pathway for chronic wound repair. Full article

Sponge spicules have emerged as promising biomaterial scaffolds due to their biocompatibility and unique structural properties; however, achieving stable and bioactive functionalization remains a key challenge. The tripeptide GHK is known to promote collagen synthesis and wound repair, yet its therapeutic efficacy is often limited by rapid diffusion and instability. Here, we report ALTUM, a thiol-functionalized sponge spicule composite in which GHK is covalently conjugated via disulfide linkage to enable controlled and redox-responsive peptide delivery. ALTUM exhibited sustained GHK retention under physiological and storage conditions, while exposure to reduced glutathione (GSH) selectively accelerated peptide release through disulfide bond cleavage. This dual release behavior—long-term stability combined with reduction-triggered activation—distinguishes ALTUM from conventional delivery systems. The composite also demonstrated structural stability under thermal, cyclic, and photostability conditions. In an artificial human skin model, ALTUM enhanced dermal penetration of GHK and significantly increased collagen deposition in the dermal layer, demonstrating its capacity to promote collagen production within deeper skin tissue, compared to simple spicule–peptide mixtures. ALTUM was fabricated at an optimized spicule-to-peptide ratio of 3% (w/w), preserving the needle-shaped spicule morphology after surface modification. In vitro, ALTUM exhibited a sustained release profile, with GHK release markedly accelerated in the presence of 10 mM glutathione (GSH) compared with non-reductive conditions, reaching approximately 60% cumulative release over 35 days. In the bioprinted artificial human skin model, ALTUM delivered 9.72 ng/cm² of GHK, more than five-fold higher than the physical mixture of spicules and free GHK (1.9 ng/cm²), and significantly increased type I collagen expression in human dermal fibroblasts. Mechanistically, ALTUM-mediated delivery was associated with increased TGF-β expression and engagement of the SMAD signaling pathway, as indicated by increased phosphorylation of SMAD2/3, consistent with involvement of the TGF-β–SMAD axis in the observed collagen induction. Collectively, these findings establish ALTUM as a structurally stable, redox-responsive dermal delivery platform that enhances collagen synthesis and skin regeneration. Full article

Background/Objective: Ultraviolet A and B (UVAB) radiation is a major environmental factor that induces DNA damage and upregulates programmed death-ligand 1 (PD-L1) expression in skin cells, thereby contributing to immune evasion and impaired tissue repair. This study evaluated the protective effects of two purified compounds, Cinnamtannin B1 (CTB-1) and Cinnamtannin D1 (CTD-1), as well as cinnamon extract, in UVAB-irradiated human keratinocyte HaCaT cells. Methods: HaCaT cells were exposed to low (20 kJ/m² UVA, 1.3 kJ/m² UVB), medium (30 kJ/m² UVA, 2 kJ/m² UVB), and high (40 kJ/m² UVA, 2.7 kJ/m² UVB) UVAB doses of UVAB radiation. Dose-dependent effects of CTB-1 and CTD-1 (0, 5, 10, 25, and 50 µg/ mL) and cinnamon extract (0, 5, 10, 50, and 100 µg/mL), as well as time-dependent effects (12, 24, and 72 h), were evaluated by measuring PD-L1 expression, cell viability, and DNA damage. Results: CTD-1 was the most effective compound, significantly reducing UVAB-induced PD-L1 expression and DNA double-strand breaks without compromising cell viability. CTB-1 also demonstrated protective effects at specific doses and time points; however, higher concentrations reduced cell viability. Cinnamon extract was protective at low concentrations but cytotoxic at higher doses. Conclusions: CTD-1, CTB-1, and cinnamon extract attenuated UVAB-induced cellular damage in HaCaT cells, with CTD-1 demonstrating the most favorable protective profile. These findings support the potential of cinnamon-derived compounds as therapeutic candidates for preventing UVAB-induced skin damage and immune dysregulation. Full article

Thymosin beta-4 (TB4) and the related compound commonly referred to as TB-500 are widely discussed in tissue healing and musculoskeletal medicine, but the scope and nature of the supporting literature remain unclear. We conducted a scoping review to map the evidence on TB4 and TB-500 in tissue healing, regeneration, and musculoskeletal repair. PubMed, Europe PMC, and ClinicalTrials.gov were searched through March 2026. English-language in vitro, animal, human, and registered clinical trial sources directly evaluating TB4, TB-500, or included derivatives in repair-related contexts were eligible. Of 1772 records identified, 80 studies were included. The evidence base was weighted toward mixed and in vitro designs, and most studies evaluated TB4 rather than TB-500. The most common tissue categories were wound/skin/soft tissue, vascular/endothelial, ocular/cornea, and bone. Direct musculoskeletal tissue categories such as tendon, ligament, muscle, cartilage, and spine/intervertebral disc were comparatively sparse. Human evidence was concentrated in ocular/cornea and wound/skin/soft tissue settings, whereas direct TB-500 evidence was limited to a single included study. Overall, the mapped literature supports the popular interest in several repair-related pathways but remains unevenly distributed and largely preclinical, with limited human evidence directly relevant to musculoskeletal applications. Full article

Extracellular vesicles (EVs), particularly small extracellular vesicles (sEVs), are lipid bilayer-delimited particles involved in intercellular communication through the transfer of proteins, lipids, and nucleic acids; many products and studies in aesthetic medicine refer to these preparations as exosomes, although endosomal origin is not always demonstrated. This review examines current evidence on the mechanisms, clinical effectiveness, safety, therapeutic applications, and regulatory challenges of EV- and sEV-based interventions, complemented by an exploratory qualitative assessment of physicians’ perceptions regarding clinical implementation. A narrative review of studies indexed in Scopus and PubMed was conducted with emphasis on skin rejuvenation, hair restoration, wound healing, pigmentation disorders, and inflammatory dermatoses, and responses from 12 aesthetic physicians in Colombia were analyzed qualitatively. Available evidence suggests that EVs/sEVs may promote extracellular matrix remodeling, angiogenesis, immunomodulation, and tissue repair, with potential benefits across several aesthetic and regenerative indications. However, the literature remains heterogeneous and limited by variability in biologic sources, isolation and administration protocols, insufficient high-quality clinical trials, and unresolved regulatory issues. Reports of adverse reactions linked to unapproved products marketed as exosome-based formulations further highlight the need for stronger oversight. EVs, particularly sEVs, often referred to as exosomes in the aesthetic literature, remain a promising therapeutic platform, but safe clinical integration requires rigorous validation, technical standardization, and robust regulatory frameworks. Full article

Cutaneous leishmaniasis (CL) is the most common clinical form of leishmaniasis, characterized by persistent skin ulcers and nodules. Standard chemotherapeutic agents have substantial toxicity and do nothing to repair the damaged tissue, an unmet need that motivates the search for adjunctive strategies. Mesenchymal stem cells (MSCs) can modulate macrophage activity and support tissue regeneration, yet their role in CL has received limited attention. In this study, we tested whether bone marrow-derived MSCs (BM-MSCs) could attenuate Leishmania mexicana-induced inflammation and facilitate skin repair. Indirect co-culture of BM-MSCs with infected RAW264.7 macrophages shifted the macrophage phenotype from M1 toward M2, with higher IL-10 and Arg-1 expression and lower iNOS and IL-1β. In BALB/c mice with established CL, three weekly intravenous injections of BM-MSCs reduced paw swelling, improved skin histology, decreased type I collagen deposition, lowered Integrin β1 and Cytokeratin 17 expression, and reduced tissue parasite load. Immunofluorescence confirmed a predominantly M2 macrophage distribution in treated lesions. We inferred that BM-MSCs acted on both the immune and reparative aspects of the disease process, supporting their potential as an adjunct to conventional anti-leishmanial therapy. Full article

Mohs Micrographic Surgery (MMS) is considered the most conservative and preserving procedure for removing cutaneous tumors. The major disadvantage of MMS is that tumor involvement in tissue may be underestimated. This may lead to large excisions necessitating complex reconstruction with profound effects on cosmetic results. Some patients refuse complex reconstruction and demand simple closure of post-MMS skin defects. This retrospective cohort study describes our technique of serial Mohs excisions of large non-melanoma skin cancers for patients refusing flaps or skin graft reconstructions. A total of 51 patients who underwent MMS according to the described technique February 2020–May 2021 were included. The mean age was 76.5 (range 63–94) years and 55% were male. More than half of the lesions were on the nose. Mean lesion sizes were 14.25–55 mm depending on location. Most cases required two surgeries and only one needed a third surgery. Postsurgical defects were repaired using primary closure in 90% of cases. Mean follow-up was 31 months (range 6–48) with no evidence of local recurrence. In conclusion, this approach of serial excisions with MMS can be performed safely and achieve better cosmetic outcomes for patients presenting with large skin tumors of the face or other functionally important areas. Full article

Background/Objectives: Bursera bipinnata (DC.) Engl. resin (locally known as “copal blanco”) is traditionally used in Mexican ethnomedicine to treat infected wounds and skin inflammation, but the bioactive constituents underlying these effects remain largely uncharacterized. This study aimed to identify the compounds responsible for the wound-healing properties of the resin through bioactivity-guided fractionation and to evaluate their anti-inflammatory and antibacterial activities as complementary mechanisms supporting tissue repair. Methods: Crude resin (1.2–5.0 mg/mL) was assayed for anti-inflammatory activity in the TPA-induced ear-edema model in BALB/c mice, for antibacterial activity (MIC) against six clinically relevant strains, and for wound-healing activity in a murine excisional model with pirfenidone (PFD) as the reference drug (n = 5 per group). Bioactivity-guided fractionation followed by spectroscopic elucidation (¹H- and ¹³C-NMR, IR, EI-MS) led to the isolation of five constituents. Stigmasterol, the most active compound, was subsequently evaluated in an LPS-induced systemic inflammation model (oral administration, 20 mg/kg/day × 3 days) to characterize its immunomodulatory profile (TNF-α, IL-1β, IL-6, IFN-γ, IL-10) and in the wound-healing model to quantify local IL-6, IL-10 and TGF-β1 in skin homogenates. Results: The crude resin (5.0 mg/mL) achieved 99.63% wound closure at day 12 and a 49.08% reduction in TPA-induced ear edema, comparable to indomethacin (55.76%). The resin displayed selective antibacterial activity against Streptococcus pyogenes (MIC 125 µg/mL) and Salmonella typhimurium (MIC 250 µg/mL). Bioactivity-guided fractionation yielded the phytosterol stigmasterol (1), three lupane-type triterpenoids (lupeol acetate (2), lupenone (3), 3-epilupeol (5)), and the sesquiterpenoid caryophyllene oxide (4). At an equimolar 1 µM concentration, stigmasterol (1) shortened the mean wound-healing time to 10.3 ± 0.4 days, comparable to pirfenidone, and was associated with attenuation of systemic TNF-α, IL-1β and IL-6 peaks and with sustained local IL-10 and TGF-β1 expression. Histological assessment confirmed accelerated re-epithelialization and improved collagen organization. The resin was non-irritant in the OECD 404 acute dermal test (Primary Irritation Index = 0.00). Conclusions: These findings provide pharmacological evidence supporting the traditional use of B. bipinnata resin for wound healing. Stigmasterol (1), together with the lupane-type triterpenoids lupenone (3) and 3-epilupeol (5), were identified as key bioactive constituents. The data are consistent with a coordinated immunomodulation, in which stigmasterol is associated with reduced systemic pro-inflammatory signalling and increased local IL-10/TGF-β1 expression, an interpretation that should be confirmed in chronic and impaired wound-healing models. Full article