Search Results (2,204)

Tissue engineering and regenerative medicine are shifting from passive tissue replacement toward instructive platforms that regulate cellular behavior, immune responses, vascularization, and extracellular matrix remodeling. This review examines recent advances in natural, synthetic, composite, and stimuli-responsive biomaterials, biofabrication and 3D bioprinting, stem and progenitor cell therapies, extracellular vesicles and other cell-free products, immunomodulatory scaffolds, skin organoids and organ-on-a-chip systems, nanotechnology, and artificial intelligence-assisted design. Particular emphasis is placed on plastic, reconstructive, and aesthetic applications, including skin and wound repair, craniofacial bone and cartilage regeneration, peripheral nerve reconstruction, vascularization, and dental and periodontal repair. The review also considers biomodulators and skinboosters as emerging regenerative-aesthetic interventions that aim to improve dermal hydration, fibroblast activity, collagen remodeling, and skin quality rather than provide volume replacement alone. Importantly, these technologies differ substantially in translational maturity, ranging from in vitro and preclinical platforms to early clinical interventions, established clinical products, and commercially available treatments for which durable regenerative efficacy remains incompletely validated. Throughout this review, biological plausibility and preclinical efficacy are therefore distinguished from human clinical evidence, regulatory or established clinical use, and commercial availability. Progress will require standardized characterization, mechanism-linked potency assays, clinically relevant models, and outcome measures that capture functional integration, durability, safety, and aesthetic performance. Full article

Cannabis use has increased substantially in the United States, driven by broader legalization, decriminalization, and expanding medical and recreational availability. For facial plastic surgeons, the clinical implications remain difficult to define because “cannabis use” encompasses heterogeneous products and routes, including smoked flower, vaping, concentrates, edibles, pharmaceutical cannabinoids, topical cannabidiol (CBD), and frequent co-use with tobacco or nicotine. Current evidence suggests that systemic cannabis use, particularly inhaled or heavy perioperative use, may be associated with increased surgical complications in selected populations; however, existing studies are limited by retrospective design, inconsistent exposure definitions, inadequate dose and route characterization, and confounding by tobacco use and comorbidities. Cannabinoids exert biologic effects through the endocannabinoid system, particularly CB1 and CB2 receptors, which are expressed in the central nervous system, immune cells, vasculature, and skin. These pathways influence inflammation, keratinocyte proliferation, fibroblast activity, angiogenesis, immune surveillance, pain signaling, and tissue remodeling. The net effect of cannabinoid exposure on wound healing is likely context dependent, varying based on receptor expression, wound-healing phase, route of administration, cannabinoid composition, local tissue environment, and patient-specific risk factors. Preclinical and early dermatologic literature suggests potential therapeutic roles for topical cannabinoids, especially CBD, in modulating inflammation and epithelial repair. In contrast, systemic perioperative cannabis use has been associated in several surgical cohorts with infection, delayed healing, hematoma, nonunion, and reoperation. Evidence specific to facial plastic surgery remains sparse. The most directly relevant study evaluated cannabis and tobacco use in patients undergoing operative mandibular fracture repair. Cannabis-only use was not associated with increased complications, although the cohort was small; concurrent cannabis and tobacco use was associated with higher rates of surgical site infection, facial nonunion, abscess, debridement, and malocclusion. To date, no published studies address cannabis-associated outcomes in rhinoplasty, rhytidectomy, blepharoplasty, browlift, or facial rejuvenation. This review summarizes the biologic rationale, available surgical evidence, and clinical considerations for incorporating cannabis use into individualized perioperative risk assessment in facial plastic surgery. Full article

Background: Plants have been traditionally used for centuries to treat wounds and, over time, have been tested for their healing properties. There is a constant search for new natural resources that could be used to develop various topical wound care products. Methods: A comprehensive search of the literature was conducted in PubMed/MEDLINE, Scopus, and Web of Science databases (2022–2026) in accordance with the PRISMA 2020 guidelines. Included studies focused on current in vitro and in vivo research on hydrogels containing plant extracts from the Asteraceae and Lamiaceae families and their potential application in wound healing and skin regeneration. Results: An analysis of 24 included studies confirms that both families include interesting and valuable plants with antioxidant, antimicrobial and anti-inflammatory properties; these plants also influence collagen deposition, fibroblast proliferation, and epithelialization, and reduce the risk of infection, thereby contributing to faster wound healing. The most frequently tested phytoextract in this respect was Calendula officinalis (Asteraceae) incorporated into a hydrogel. A variety of materials, including natural, semi-synthetic, and synthetic polymers, as well as hybrid matrix, but also diverse formulation strategies, from simple solutions to more advanced and modern methods, have been used to produce hydrogels. Conclusions: This systematic review summarizes the current evidence, highlights directions and possibilities for the use of phytoextract-based hydrogels, and discusses limitations and future perspectives in the development of effective externally applied formulations to support wound healing. Full article

The aim of the study was to synthesize nanocomposites based on cerium orthophosphate stabilized with citrate at different ratios for biomedical applications, and to evaluate its safety in different animal species. Nanocomposites were synthesized using four different initial mass ratios of Ce(NO₃)₃ × 6H₂O to citric acid: 1:5 (Ce:5CA), 1:3 (Ce:3CA), 1:1 (Ce:1CA), and 1:0.5 (Ce:0.5CA). The obtained products were characterized by a series of physicochemical methods including X-ray diffraction, transmission electron microscopy, and IR spectroscopy. Biomedical studies of the sols were performed to evaluate redox activity and their effects on the metabolism and proliferation of human fibroblasts. Safety studies were carried out in different animal species, including determination of the acute toxicity of the selected nanocomposite following application to intact skin and intragastric administration, as well as determination of subchronic toxicity using a model of acute experimental full-thickness skin wounds. According to the physicochemical studies, all synthesized nanocomposites contained nanocrystals with bimodal dimensions (width 3–10 nm, length 15–40 nm) and diffraction peaks characteristic of CePO₄. IR spectroscopy demonstrated the formation of new chemical bonds. Antioxidant activity was observed for the Ce:3CA, Ce:1CA, and Ce:0.5CA samples, being most pronounced for Ce:1–0.5CA, whose antioxidant capacity exceeded that of ascorbic acid. In contrast, Ce:5CA exhibited pro-oxidant activity at all tested concentrations. Biocompatibility with human cells was demonstrated. Ce:0.5CA was identified as the most promising candidate for biomedical applications owing to its highest regenerative and antioxidant potential and its demonstrated safety in animals following topical and intragastric administration, as well as in wound models. Histomorphological examination of the internal organs supported the safety and potential of the developed nanocomposites for skin regeneration and wound healing. Full article

Skin photoaging, primarily driven by UVA radiation, is characterized by the accumulation of senescent fibroblasts and the degradation of the extracellular matrix (ECM). While the roles of reactive oxygen species (ROS) and matrix metalloproteinases (MMPs) are well-documented, the regulatory impact of post-translational glycosylation in this process remains poorly understood. We established a UVA-induced photoaging model in human dermal fibroblasts (HDFs) and employed bulk mRNA-seq and high-throughput lectin microarrays to profile glycomic alterations. The functional role of the sialyltransferase ST6GAL1 was investigated through pharmacological inhibition of cellular sialylation (3Fax-Neu5Ac), siRNA-mediated knockdown, and gain-of-function overexpression. Mechanistic insights were gained via RAS-ERK pathway analysis and validated in a 3D reconstructed human full-thickness skin model (T-Skin™). Glycomic profiling revealed that UVA irradiation triggers a broad increase in α2,6-sialylation in HDFs. We identified ST6GAL1 as the primary enzymatic driver of this remodeling, with its expression upregulated in both photoaged HDFs and 3D skin models. Functional assays demonstrated that ST6GAL1 overexpression induces hallmark features of photoaging, including p16, MMP and γ-H2AX upregulation, G0/G1 cell cycle arrest and increased SA-β-gal activity. Conversely, pharmacological or genetic inhibition of ST6GAL1 effectively mitigated the photoaged phenotype. Mechanistically, ST6GAL1 regulates the expression of p16 via the activation of the RAS-ERK signaling cascade. Our study identifies ST6GAL1-mediated α2,6-sialylation as a novel functional hallmark of skin photoaging, highlighting the association of ST6GAL1 with the RAS-ERK-p16 axis as a potential regulator for targeting UVA-induced skin photoaging and dermal senescence. Full article

Background/Objectives: Triple negative breast cancer remains the most difficult breast cancer to treat as there are no specific targeted therapies. The tumor stroma is recognized as essential for the development of solid tumors. Cancer associated myofibroblasts are known to play a major role in the construction of a tumor microenvironment conducive to tumor progression. Therefore, we established a co-culture system to identify potential molecular targets controlling myofibroblast conversion. Methods: Co-cultures of MDA-MB-468 triple negative breast cancer cells and skin fibroblasts were either mixed prior to seeding or seeded individually on opposite sides of a culture dish and incubated in complete medium. Inhibitors were preincubated with cells for 1 h. Inflammatory cytokines were measured by ELISA. Proteins were analyzed using the Wes-Protein Simple System. Immunostaining was visualized using a Hamamatsu Photonics Nanozoomer. Statistical analysis was done by student’s t-test and one-way ANOVA. Results: The data indicate that co-culturing the cells promotes myofibroblast differentiation and cytokine release and this requires direct contact between the two cell types. Both myofibroblast conversion and cytokine release were prevented by inhibitors of TLR5, TGF-β and EDA-fibronectin. Conclusions: Data suggest that the TLR5 receptor on the MDA-MB-468 cells binds to EDA-fibronectin expressed by fibroblasts thus inducing inflammatory cytokine expression. Expression of EDA fibronectin is regulated through TGF-β whose synthesis is induced by TLR5 signaling in the tumor cells. The data are consistent with a model in which TLR5-mediated crosstalk between the cancer cells and the stromal fibroblasts creates a tissue microenvironment conducive to tumor growth and metastasis. Full article

Industrial hemp is a chemically rich plant increasingly explored within sustainable production systems aimed at the full utilization of all plant fractions. While hemp inflorescences have been extensively investigated, the biological potential of seed-depleted infructescences remains largely underexplored. This study compared essential oils (EOs) distilled from inflorescences and seed-depleted infructescences of hemp (Cannabis sativa L. cv. Futura 75). Their chemical composition was determined by gas chromatography–mass spectrometry (GC–MS), and their cytotoxicity, hemocompatibility, effects on blood coagulation, and antibacterial activity against a panel of 11 Gram-positive, Gram-negative, and microaerophilic bacterial strains were evaluated. The major EO constituents included α-Pinene, (E)-Caryophyllene, Myrcene, α-Humulene, Caryophyllene oxide, and Cannabidiol. EOs obtained from seed-depleted infructescences exhibited distinct chemical profiles, low cytotoxicity toward BJ human skin fibroblasts, minimal haemolytic activity, no significant effects on blood coagulation, and, in most cases, stronger antibacterial activity than inflorescence-derived EOs. Particularly high activity was observed against skin- and oral-associated bacteria, including Cutibacterium acnes and Streptococcus species. These findings demonstrate that seed-depleted infructescences represent underutilized post-harvest biomass and a valuable and sustainable source of biologically active EOs, supporting their further investigation for potential pharmaceutical, cosmetic, and oral healthcare applications. Full article

Background: Mitochondrial dysfunction is increasingly recognized as a central contributor to intrinsic skin aging, photoaging, cellular senescence, impaired extracellular-matrix homeostasis, dysregulated pigmentation, and delayed recovery after energy-based or minimally invasive procedures. Pyrroloquinoline quinone (PQQ) is a redox-active ortho-quinone that has attracted interest because it can participate in repeated redox cycling, protect mitochondrial function, and activate signaling associated with mitochondrial biogenesis. Objective: This narrative review evaluates the mechanistic basis, available dermatologic evidence, translational opportunities, and major uncertainties surrounding PQQ as a mitochondrial rejuvenation strategy in aesthetic dermatology. Methods: PubMed/MEDLINE and Europe PMC were searched from database inception through 10 August 2026 using PQQ-, mitochondrial-, skin-, delivery-, and safety-related terms; reference lists were also screened. Mechanistic, preclinical, skin-focused, human, and regulatory evidence was synthesized narratively. Results: Experimental studies support PQQ-mediated activation of mitochondrial biogenesis pathways and protection against oxidative injury in several cell and animal systems. Skin-specific evidence includes attenuation of oxidative stress, DNA damage, senescence markers, and matrix metalloproteinases in accelerated-aging mouse models; protection of UVA-exposed human dermal fibroblasts; suppression of UVB-induced caspase-1 release in keratinocytes; a small oral dry-skin study; and a multi-ingredient topical study containing an allyl PQQ derivative. These studies do not establish PQQ-specific clinical aesthetic efficacy. Conclusion: PQQ is a biologically plausible mitochondrial-support compound, but it should currently be regarded as an investigational ingredient rather than an established aesthetic treatment. Carefully designed formulation, toxicology, dose-finding, biomarker, and randomized clinical studies are required before claims regarding wrinkle reduction, pigment improvement, enhanced collagen production, or accelerated post-procedure recovery can be justified. Full article

Ultraviolet B (UVB) irradiation is a major environmental factor contributing to skin photoaging by inducing oxidative stress, apoptosis, inflammation, and extracellular matrix degradation in dermal fibroblasts. This study investigated the photoprotective effects of Thua Nao, a Thai fermented soybean, against UVB-induced human dermal fibroblast damage, and explored its underlying mechanisms. The dichloromethane fraction of Thua Nao (TN-DC) most effectively mitigated UVB-induced cell death. HPLC analysis identified daidzein and glycitein as the major constituent isoflavones in TN-DC that protect fibroblasts against UVB-induced cellular damage. Mechanistically, they reduced apoptosis by suppressing caspase-9 and poly (ADP-ribose) polymerase activation and preserving mitochondrial membrane potential. Additionally, they suppressed inflammatory mediators including interleukin-6, interleukin-8, inducible nitric oxide synthase, and cyclooxygenase-2 and prevented collagen loss. These protective outcomes correlated with decreased intracellular reactive oxygen species and upregulated endogenous antioxidant enzymes including superoxide dismutase 1 and heme oxygenase. Signaling pathway analysis revealed that TN-DC activated the pro-survival extracellular-signal-regulated kinase and Akt pathways in UVB-exposed cells. Conversely, daidzein and glycitein selectively attenuated c-Jun N-terminal kinase activation, downregulating downstream pro-inflammatory cytokines and mediators. Collectively, these findings demonstrate that TN-DC protects human dermal fibroblasts against UVB-induced photoaging primarily by enhancing endogenous antioxidant defense, thereby preserving cellular homeostasis through coordinated regulation of oxidative stress-responsive signaling pathways. Full article

Multiple acyl-CoA dehydrogenase deficiency (MADD) is considered an autosomal recessive disorder; yet, recent findings suggest up to 10% of cases may result from heterozygous electron transfer flavoprotein dehydrogenase (ETFDH) variants exhibiting dominant or dominant-like effects. Here, a novel heterozygous ETFDH variant (c.1798A>C, p.Asn600His) was identified within a three-generation family. The grandfather presented with muscular weakness at age 35, and the father developed similar symptoms at 19 following a tonsillectomy. Both were diagnosed with MADD based on muscle biopsies revealing neutral lipid accumulation and acylcarnitine profiles and responded fully to riboflavin therapy (150 mg/day). The two siblings, aged 8 and 10, carry the same mutation and show increased acyl-carnitine levels but remain asymptomatic due to early riboflavin treatment. Skin fibroblasts from affected individuals were immortalized and subjected to normal and reduced riboflavin levels. Gene expression analysis demonstrated unchanged ETFDH RNA but reduced protein levels in mutant cells, particularly under low riboflavin. Structural modelling suggested the Asn600His substitution destabilizes the protein, diminishing its mitochondrial function. Proximity ligation assays indicated a decreased interaction with mitochondrial complex III, while oxygen consumption via fatty acid oxidation was impaired, especially at reduced riboflavin. The novel ETFDH variant found in this family gives a possible dominant pattern of inheritance for MADD, where a single mutant allele impairs the mitochondrial metabolism, particularly under riboflavin-deficient conditions, and highlights the importance of early riboflavin supplementation in preventing clinical symptoms. Full article

Background: Loss of epithelial integrity leaves the wound bed open to opportunistic bacterial colonization, and the risk of secondary infection persists for as long as the defect remains unclosed. Wound dressings must therefore provide an immediate external barrier while accelerating restoration of the skin’s own barrier. This study aims to develop and evaluate a bioactive nanotechnological platform comprising dexpanthenol (Dxp)-engineered extracellular vesicles (EVs) embedded within cross-linked hyaluronic acid hydrogels (HA@Dxp-engineered EVs) for targeted wound treatment and protection against external contaminants. Methods: EVs were engineered via exogenous (extrusion; Exo EV) and endogenous (co-incubation; Endo EV) strategies to encapsulate Dxp. The physicochemical properties of the HA@Dxp-engineered EV systems were characterized, and their therapeutic efficacy was validated through in vitro assays, including fibroblast migration and endothelial tube formation, and in vivo using a full-thickness excisional wound model in mice. Results: Both engineering strategies successfully encapsulated Dxp while preserving the structural integrity of the EVs. The HA hydrogel enabled sustained EV release and provided a physical barrier. In vitro, HA@Endo EVs significantly promoted fibroblast proliferation, migration, and the formation of mature capillary-like networks in HUVECs compared to controls. In vivo, the HA@Endo EV group demonstrated accelerated wound closure, achieving 99.88% healing by day 10, and promoted tissue remodeling with upregulated expression of COL1A1, VEGF, and HIF-1α. Conclusions: The HA@Endo EV system provides a dual-action strategy against secondary infection risk. It supplies an immediate physical barrier over the wound bed and simultaneously accelerates re-epithelialization, thereby shortening the interval during which the tissue remains exposed. Full article

The telomere is one of the biological hallmarks of skin aging. Sodium acetylated hyaluronate (SAH) is an acetylated derivative of sodium hyaluronate, produced by a grafting technology that confers higher resistance to hyaluronidase. This study aimed to explore whether SAH is associated with telomere-related endpoints and with clinical signs of skin aging. Two vitro studies were performed, assessing telomerase activity in human adult keratinocytes and telomere length in human normal fibroblasts by quantitative PCR (qPCR) assay kits, with or without SAH. A randomized, split-face, double-centered, double-blind, placebo-controlled clinical trial was then conducted on 44 Caucasian and Asian female volunteers, comparing a facial cream containing 0.1% SAH with a placebo cream over 28 days; crow’s feet wrinkle depth, area, and volume, under-eye roughness (Rz), elasticity (R2), and firmness (F4) were measured by PRIMOS 3D and Cutometer^® MPA 580 at baseline, day 7, and day 28. In vitro, only the highest SAH concentration (0.15%) was associated with a significant increase in telomerase activity and in telomere length versus control, whereas lower concentrations had no significant effect. Clinically, the SAH cream significantly reduced crow’s feet wrinkle volume and area, improved skin elasticity, and reduced under-eye roughness versus placebo, with non-significant trends for wrinkle depth and firmness. These exploratory findings make SAH an interesting active ingredient for anti-aging skincare cosmetics, combining a curative dimension (clinical improvement of skin-aging parameters) with a preventive dimension (telomere preservation observed in vitro for the first time), and warrant further mechanistic investigation. Full article

Skin photoaging is primarily induced by ultraviolet (UV) radiation and is accompanied by extracellular matrix (ECM) degradation, abnormal pigmentation, and loss of skin elasticity. Excessive melanin synthesis represents a key cause of pigmentary skin disorders. Natural polyphenols with dual skin-whitening and anti-photoaging activities have attracted increasing attention as cosmetic ingredients. This study examined the effects of polyphenol-enriched fraction from the brown alga Sargassum fusiforme (SFP). Zebrafish embryos and human melanoma A375 cells were used to evaluate the depigmenting efficacy of SFP, while UVA-induced human dermal fibroblasts (HDFs) were employed to assess its anti-photoaging activity. SFP significantly decreased melanin levels in both models in a dose-dependent and reversible manner by suppressing tyrosinase activity. In terms of anti-photoaging effects, SFP markedly suppressed UVA-induced matrix metalloproteinases (MMPs) expression and elevated key ECM components, including type I collagen, elastin, and hyaluronic acid. In conclusion, SFP exerts dual beneficial effects by attenuating melanogenesis via tyrosinase inhibition and alleviating photoaging damage by suppressing MMPs to protect ECM. These results provide a scientific foundation for the use of SFP as a dual-purpose natural cosmetic ingredient with significant potential in the cosmetics sector. Full article

Bioactive food ingredients that regulate the gut microbiota are promising dietary strategies for supporting systemic health, but their roles in skin photoaging remain insufficiently defined. Qiongyu Gao (QYG), a classical food–medicine homologous formula composed of Rehmanniae Radix, Panax ginseng, and Poria cocos, was evaluated as an oral functional food candidate for UV-induced skin photoaging. QYG was chemically characterized by HPLC and UPLC–QTOF–MS/MS. Young and aged mice were subjected to D-galactose plus UVA/UVB exposure and orally administered QYG, followed by skin transcriptomics, gut microbiota sequencing, serum metabolomics, and validation in UVB-injured primary dermal fibroblasts. QYG alleviated wrinkle formation, epidermal thickening, oxidative stress, inflammation, extracellular matrix degradation, collagen disorganization, and hyaluronic acid loss. Multi-omics analysis showed that QYG selectively remodeled gut microbiota, enriching Lactobacillus-, Bifidobacterium-, and Akkermansia-associated taxa, regulated serum metabolites related to energy and lipid metabolism, and enriched mitochondrial energy metabolism-related pathways in photoaged skin. In fibroblasts, QYG-containing serum restored mitochondrial membrane potential, reduced ROS accumulation and cellular senescence, and regulated AMPK/PGC-1α-associated markers. These findings support QYG as a promising food–medicine homologous functional food candidate for skin health maintenance through gut microbiota-associated systemic metabolic regulation. Full article

Excessive ultraviolet A (UVA) irradiation disrupts extracellular matrix (ECM) homeostasis in skin photoaging by impairing the balance between synthesis and degradation, yet whether silk fibroin peptide (SF), a small bioactive peptide from Bombyx mori, can restore this balance through mechanotransduction pathways remains unknown. Herein, we demonstrate that SF dose-dependently rescues human dermal fibroblasts (HDFs) from UVA-induced oxidative stress, senescence, and ECM disintegration. Notably, SF not only suppresses reactive oxygen species (ROS) and restores activities of antioxidant enzymes, but is also associated with the recovery of the ITGB1-FAK mechanotransduction axis, as evidenced by restored fibronectin levels and increased focal adhesion kinase (FAK) phosphorylation, whereas integrin β1 (ITGB1) expression itself was not significantly altered. This mechanosensory recovery is accompanied by restoration of downstream transforming growth factor-β (TGF-β)/Smad signaling, upregulation of COL1A1, COL3A1 and ELN transcription, and simultaneous suppression of MMP1, MMP3 and MMP9. Unlike conventional antioxidants or exogenous collagen supplements that merely counteract oxidative damage or provide structural substitutes, SF may facilitate recovery of the disrupted cell–matrix interface potentially through modulation of integrin-mediated mechanochemical signal conversion, which may contribute to ECM homeostasis restoration. Collectively, SF promotes mechanotransduction, offering a potential paradigm for anti-aging strategies that target ECM homeostasis through integrin signaling. Full article