Search Results (707)

Bone-associated pathologies are major contributors to chronic pathology statistics. Current gold standard treatments present limitations such as the ability to act as scaffolds whilst effectively delivering medications to promote cellular proliferation. Recent advancements in biomaterials have suggested whey protein isolate (WPI) hydrogel as a potential candidate to act as a scaffold with the capacity for drug delivery for bone regeneration. In this study, we investigate whey protein isolate hydrogels enhanced with the phytocannabinoid cannabidiol (CBD). The use of CBD in WPI hydrogels for bone regeneration is original. The results suggest that CBD was successfully incorporated into the hydrogels bound potentially through hydrophobic interactions formed between hydrophobic patches of the protein and the hydrophobic cannabinoid. The incorporation of CBD into the WPI hydrogels improved the mechanical strength of the hydrogels. The Young’s modulus was improved from 2700 kPa ± 117 kPa to 7100 kPa ± 97 kPa when compared to the WPI control, without plant-derived cannabinoids, to the WPI with the maximum CBD concentration. Furthermore, statistically significant differences for both Young’s modulus and compressive strength were observable between the WPI control and CBD hydrogel variables. The release of CBD from the WPI hydrogels was confirmed with the results suggesting a maximum release of 20 μM over the 5-day period. Furthermore, the hydrogels supported the proliferation and synthesis of collagen and calcium, as well as the alkaline phosphatase activity of MC3T3-E1 pre-osteoblasts, which demonstrates the potential of WPI/CBD hydrogels as a biomaterial for osseous tissue regeneration. Full article

Background: The extracellular matrix (ECM), primarily composed of collagen and elastin synthesized by dermal fibroblasts, is critical for mesenchymal tissue integrity. Fibroblast phenotypes vary significantly with the anatomical location and developmental stage. Fetal skin, particularly prior to 14 weeks of gestation, exhibits a simplified structure compared to adult skin, characterized by a thin, loose dermal matrix and a single-layered epithelium. Objectives: This study aimed to characterize and functionally compare homogenous progenitor fetal fibroblast (PFF) populations derived from 14-week-old fetal skin with fibroblasts isolated from adult burn patients. Methods: We evaluated the proliferative capacity, collagen synthesis, and differentiation potential (adipogenesis and osteogenesis) of PFF and adult burn patient fibroblasts. Furthermore, we assessed their ability to support skin regeneration using a de-epidermized dermis (DED) model seeded with both PFF and patient-derived keratinocytes. The stability of PFF characteristics was monitored across multiple passages (P5–P12). Results: PFF demonstrated a 2–4-fold increase in proliferation rate and a 30–50% enhancement in collagen production in vitro compared to adult fibroblasts. Notably, PFF exhibited a consistent lack of adipogenic and osteogenic differentiation, an attribute distinct from adult fibroblasts. In the DED model, PFF, even at a low fibroblast-to-keratinocyte ratio (1:5), effectively facilitated the formation of well-organized skin structures, including rete ridges, surpassing the performance of adult fibroblasts and adipose-derived cells. These properties remained stable over multiple passages. Conclusions: The unique attributes of PFF, likely attributable to the simplified microenvironment (i.e., collagen organization) of developing fetal tissue, positions them as a promising source for cell-based therapies. Their inherent high collagen synthesis capacity is particularly advantageous for wound healing applications. Consequently, PFF represent a consistent and readily available resource for developing “off-the-freezer” cutaneous cell therapies, potentially enabling accelerated and improved treatment of severe burn injuries. Full article

Innovation in oral implantology is constantly on the move, with a constant search for new biomaterials to overcome many of the limitations of the biomaterials used in current implantable medical devices. This study explores the biocompatibility of an innovative 5% calcium-to-zirconia (Ca-SZ) coating deposited by PVD on TA6V substrates for use in oral implantology. In order to determine the contribution of the Ca-SZ coating, an in vitro biocompatibility study was carried out to assess the potential influence of the Ca-SZ coating (1) on the viability and proliferation of saos-2 and HaCaT cells over a short-term exposure period of 96 h, (2) on the synthesis of pro-inflammatory cytokines, and (3) on the synthesis of osteogenic differentiation markers over a long-term exposure period of 21 days, in comparison with reference biomaterials. The sampling consisted of n = 3 biological replicates, and a p-value of <0.05 was used as the threshold for statistical significance. Viability and proliferation kinetics to WST-1 and CyQUANT NF, respectively, showed improved viability/proliferation of Ca-SZ exposed to both cell lines independently. The TNF-alpha and IL-6 assays revealed reduced levels of cytokines compared with the reference biomaterials, including the control groups. In parallel, in Saos-2 cells exposed to Ca-SZ for 21 days under osteogenic conditions increased expression of osteogenic markers, such as the synthesis of soluble collagens, alkaline phosphatase (ALP), osteopontin, and osteocalcin, reflecting dynamic and facilitated osteoblastic differentiation, which was supported by the formation of hydroxyapatite (HA) crystals observed by SEM micrograph and confirmed by EDS mapping. In conclusion, Ca-SZ demonstrates an overall better biocompatibility compared with reference biomaterials, linked to a bioactive interaction of calcium, promoting cell proliferation and differentiation for optimal osteointegration, underlining its potential as a relevant innovation for next-generation implants. Full article

Genetic predisposition, environmental factors, lifestyle choices, and physical activity influence skin quality. Regular exercise has well-documented benefits for skin physiology, including enhanced microcirculation, improved collagen synthesis, oxidative stress reduction, and modulation of inflammatory pathways. However, individual responses to physical activity vary significantly, depending on skin type, age, fitness level, and environmental exposures. Recent advances in artificial intelligence (AI) offer new opportunities for tailoring exercise programs to meet individual skin health needs. Wearable sensors and smart fitness devices provide real-time data on physiological responses (e.g., heart rate, sweat rate, and oxidative stress) and environmental parameters (e.g., UV exposure and pollution levels). AI algorithms process this data to create dynamic, adaptive exercise routines designed to maximize skin benefits while minimizing potential harm (e.g., exercise-induced oxidative stress in sensitive skin types). This review synthesizes the current evidence on the skin benefits of exercise while exploring the emerging role of AI-driven personalized physical activity as a novel tool in cosmetic dermatology. Integrating AI into fitness planning, personalized, non-invasive skincare strategies may complement traditional topical and procedural approaches, representing a step forward in precision dermatology. Full article

Background/Objectives: Patellofemoral pain (PFP) is considered a risk factor for knee osteoarthritis (OA) onset. The purpose of this study was to compare degenerative biomarkers in females with and without PFP and to determine changes in these levels, along with pain and function, over 6 months. Methods: All subjects received a knee x-ray to ensure that none had degenerative changes. Urine and serum were collected and analyzed for C-telopeptide fragments of type II collagen (CTX-II) and C-propeptide II (CP-II); these were then expressed as a cartilage degradation: cartilage synthesis ratio (CTX-II:CP-II). Subjects with PFP rated pain using a 10 cm visual analog scale, and function using the Knee injury and Osteoarthritis Outcome Scores-Patellofemoral (KOOS-PF) questionnaire. Subjects with PFP were tested at baseline and at 6 months. Results: Females with PFP had higher levels of CTX-II:CP-II than controls (p < 0.001) and these remained elevated at 6 months (p = 0.82). Females with PFP reported similar levels of pain (p = 0.30) but higher function at 6 months (p = 0.002). However, the 9.0-point increase in KOOS-PF values did not exceed the minimum important change. Conclusions: Females with PFP but no evident structural changes had more elevated biomarkers than controls. This finding suggests that this cohort may have excessive cartilage turnover which may contribute to knee OA. Full article

Sleep deprivation is a prevalent issue that disrupts the circadian rhythm of estrogen, particularly estradiol, thereby significantly affecting women’s skin health and appearance. These disruptions can impair skin barrier functionality and decrease dermal collagen synthesis. In this study, our results demonstrate that topical taurine supplementation promotes the expression of tight junction (TJ)-related proteins and enhances collagen production, effectively restoring skin homeostasis in sleep-deprived female mice. Mechanistically, taurine upregulates the expression of TMEM38B, a gene encoding the TRIC-B trimeric cation channel, resulting in increased intracellular calcium ion levels. This, in turn, promotes the upregulation of TJ-related proteins, such as ZO-1, occludin, and claudin-11 in epidermal cells, while also enhancing the expression of type III collagen in fibroblasts, thus restoring skin homeostasis. These findings suggest that taurine may serve as an alternative to estradiol, effectively improving skin homeostasis disrupted by sleep deprivation while mitigating the potential risks associated with exogenous estrogen supplementation. Collectively, these results provide preliminary insights into the protective mechanisms of taurine against sleep deprivation-induced skin impairments and establish a foundation for its potential application in treating skin conditions related to estrogen imbalances, such as skin aging in menopausal women. Full article

Nanotopography refers to the intricate surface characteristics of materials at the sub-micron (<1000 nm) and nanometer (<100 nm) scales. These topographical surface features significantly influence the physical, chemical, and biological properties of biomaterials, affecting their interactions with cells and surrounding tissues. The development of nanostructured surfaces of polymeric nanocomposites has garnered increasing attention in the fields of tissue engineering and regenerative medicine due to their ability to modulate cellular responses and enhance tissue regeneration. Various top-down and bottom-up techniques, including nanolithography, etching, deposition, laser ablation, template-assisted synthesis, and nanografting techniques, are employed to create structured surfaces on biomaterials. Additionally, nanotopographies can be fabricated using polymeric nanocomposites, with or without the integration of organic and inorganic nanomaterials, through advanced methods such as using electrospinning, layer-by-layer (LbL) assembly, sol–gel processing, in situ polymerization, 3D printing, template-assisted methods, and spin coating. The surface topography of polymeric nanocomposite scaffolds can be tailored through the incorporation of organic nanomaterials (e.g., chitosan, dextran, alginate, collagen, polydopamine, cellulose, polypyrrole) and inorganic nanomaterials (e.g., silver, gold, titania, silica, zirconia, iron oxide). The choice of fabrication technique depends on the desired surface features, material properties, and specific biomedical applications. Nanotopographical modifications on biomaterials’ surface play a crucial role in regulating cell behavior, including adhesion, proliferation, differentiation, and migration, which are critical for tissue engineering and repair. For effective tissue regeneration, it is imperative that scaffolds closely mimic the native extracellular matrix (ECM), providing a mechanical framework and topographical cues that replicate matrix elasticity and nanoscale surface features. This ECM biomimicry is vital for responding to biochemical signaling cues, orchestrating cellular functions, metabolic processes, and subsequent tissue organization. The integration of nanotopography within scaffold matrices has emerged as a pivotal regulator in the development of next-generation biomaterials designed to regulate cellular responses for enhanced tissue repair and organization. Additionally, these scaffolds with specific surface topographies, such as grooves (linear channels that guide cell alignment), pillars (protrusions), holes/pits/dots (depressions), fibrous structures (mimicking ECM fibers), and tubular arrays (array of tubular structures), are crucial for regulating cell behavior and promoting tissue repair. This review presents recent advances in the fabrication methodologies used to engineer nanotopographical microenvironments in polymeric nanocomposite tissue scaffolds through the incorporation of nanomaterials and biomolecular functionalization. Furthermore, it discusses how these modifications influence cellular interactions and tissue regeneration. Finally, the review highlights the challenges and future perspectives in nanomaterial-mediated fabrication of nanotopographical polymeric scaffolds for tissue engineering and regenerative medicine. Full article

Benzo[a]pyrene (B[a]P) is a widespread and persistent organic pollutant that poses serious threats to human health. Although its carcinogenic properties have been extensively studied, its developmental toxicity and underlying mechanisms remain poorly understood. In this study, we employed Caenorhabditis elegans (C. elegans) as a model organism to investigate the effects of B[a]P exposure during early developmental stages. To comprehensively assess B[a]P-induced developmental toxicity, we employed high-throughput sequencing along with transgenic and mutant C. elegans strains. Exposure to B[a]P at concentrations exceeding 1 mg/L significantly reduced larval body size, decreased the number of adult worms, and delayed larval-to-adult development. Furthermore, we analyzed the expression of genes involved in cuticle collagen synthesis and key components of the insulin/insulin-like growth factor signaling (IIS) pathway, including daf-2 and daf-16. These findings suggest that B[a]P-induced developmental toxicity may be associated with dysregulation of the IIS pathway. Specifically, B[a]P appears to influence the activity of the downstream transcription factor daf-16, thereby altering the expression of collagen-related genes. This disruption in collagen synthesis may contribute to delayed larval development and impaired maturation. Our study provides new insights into the environmental hazards associated with B[a]P exposure and reveals a potential mechanism underlying its developmental toxicity. Moreover, our findings highlight the critical role of collagen gene regulation during early developmental stages. These genes may serve as potential biomarkers for environmental toxicant exposure, particularly in vulnerable populations such as children undergoing critical periods of development. Full article

Skin ageing is a complex biological process influenced by cellular senescence, oxidative stress, and extracellular matrix degradation. Emerging evidence suggests that plant-derived bioactive compounds and extracellular vesicles (EVs) play a crucial role in modulating cellular homeostasis, promoting tissue regeneration, and counteracting age-related morphological and functional changes. This study investigates the impact of Haberlea rhodopensis in vitro culture extracts, native and enriched with EVs, on key cellular processes, including morphology, mitochondrial dynamics, lysosomal activity, gene expression, and genotoxicity in human dermal fibroblasts. The extracellular vesicles were identified in terms of shape, size, and morphology using dynamic light scattering, negative staining and observation under a transmission electron microscope. A comprehensive in vitro analysis was conducted utilizing light microscopy to assess cellular morphology and lysosomal mass, fluorescence microscopy for actin cytoskeletal organization, mitochondrial integrity, and nuclear morphology, and gene expression profiling for markers associated with collagen synthesis (COL1A1, COL3A1), senescence (CDKN1A), and oxidative stress response (NFE2L2). Additionally, cell cycle progression was evaluated, and genotoxicity was assessed using the neutral comet assay. Haberlea rhodopensis in vitro culture extracts and EVs were found to preserve fibroblast morphology, enhance mitochondrial mass, and upregulate collagen-related gene expression. These effects were concentration-dependent. The extracts exhibited biocompatibility with minimal genotoxic effects, indicating their potential as safe bioactive agents for skin rejuvenation. The findings suggest that Haberlea rhodopensis in vitro culture extracts and their enrichment with extracellular vesicles hold promise for cosmetic and dermatological applications, particularly in enhancing collagen production, preserving cellular integrity, and mitigating age-related alterations in skin fibroblasts. Further studies are warranted to elucidate the underlying molecular mechanisms and optimize formulation strategies for clinical translation. Full article

Background: Myocardial fibrosis in aortic stenosis (AS) is associated with a significant risk of poor clinical outcomes. Myocardial fibrosis can be evaluated using cardiovascular magnetic resonance (CMR) imaging and may be useful for risk-stratifying patients at high risk for poorer outcomes. A circulating biomarker of fibrosis may be a cheaper, more accessible alternative to CMR in lower-to-middle-income countries. This study evaluated the correlation between serum biomarkers of myocardial fibrosis (TGF-β1, PICP, and PIIINP) with CMR markers of myocardial fibrosis (T1 mapping, extracellular volume fraction (ECV), and late gadolinium enhancement (LGE)). Methods: Twenty-one high-gradient (mean gradient ≥ 40 mmHg) severe AS (aortic valve area < 1.0 cm²) participants underwent T1 mapping and LGE imaging using CMR. Blood serum was collected for enzyme-linked immunosorbent assays of the listed biomarkers. Results: Serum TGF-β1 was associated significantly with the global T1 relaxation time on CMR (r = 0.46 with 95% CI 0.03 to 0.74, p = 0.04). In the high T1 time group (1056 vs. 1023 ms), trends toward elevated serum TGF-β1 concentration (13,044 vs. 10,341 pg/mL, p = 0.08) and ECV (26% vs. 24%, p = 0.07) were observed. The high T1 and trend towards elevated TGF-β1 concentration in this group tracked adverse LV remodeling and systolic dysfunction. There were no significant associations between PICP/PIIINP and T1 mapping or between the biomarkers and LGE quantity. Conclusions: Serum TGF-β1 is a potential surrogate for diffuse interstitial fibrosis measured by T1 mapping and ECV on CMR. Serum PICP and PIIINP may be less appropriate as surrogate markers of fibrosis in view of their temporal trends over the course of AS. Larger studies are needed to validate the utility of TGF-β1 as a marker of diffuse fibrosis and to evaluate the utility of serial PICP/PIIINP measurements to predict decompensation. Full article

Tissue engineering techniques aim to improve or replace biological tissues or organs by utilizing the extracellular matrix to facilitate the repair of damaged tissues or organs. Collagen-based scaffolds offer numerous advantages, including excellent biocompatibility, low immunogenicity, biodegradability, hemostatic properties, and mechanical strength. Collagen scaffolds can reconstruct the extracellular microenvironment, promote cell adhesion, migration, proliferation, and differentiation, and play a critical role in cell-to-cell and cell-to-matrix interactions. Collagen has been extensively utilized in tissue engineering to facilitate tissue repair and organ reconstruction. This review examines the properties of collagen, including its composition, structure, biological characteristics, and role in regulating various cellular behaviors. Additionally, the preparation of cell-loaded collagen scaffolds is discussed, along with a comprehensive overview of their applications in various tissues, including skin, nerve, bone/cartilage, heart, liver, and others. Emerging strategies and future perspectives for clinical tissue repair are also presented. This review provides a comprehensive synthesis of the mechanisms underlying the use of cell-loaded collagen scaffolds as advanced biomaterials, emphasizing their potential to expand the clinical applications of collagen. Full article

Vitamin C, also known as ascorbic acid, is an essential nutrient that humans cannot synthesize, making its intake crucial for health. Discovered nearly a century ago, vitamin C is widely recognized for its ability to prevent scurvy and has become one of the most commonly used supplements. Beyond its antioxidant activity, vitamin C is pivotal in regulating lipid metabolism, promoting angiogenesis, enhancing collagen synthesis, modulating remodeling, and stabilizing the extracellular matrix. While preclinical studies have shown promising results, clinical trials have yielded inconsistent findings, due to suboptimal study design, results misinterpretation, and misleading conclusions. This review provides a holistic overview of existing evidence on the pleiotropic role of vitamin C in cardiovascular diseases, identifying both the strengths and limitations of current research and highlighting gaps in understandings in vitamin C’s underlying mechanisms. By integrating molecular insights with clinical data and evaluating the pleiotropic role of vitamin C in cardiovascular disease management and prevention, this review aims to guide future research toward personalized, evidence-based therapeutic strategies in clinical practice. Full article

Given the growing interest in natural compounds for promoting healthy aging, this study aimed to investigate the potential of cod collagen peptides (CCPs), a readily available marine resource, to extend lifespan and improve health. Lifespan assays were performed on C. elegans treated with different concentrations of CCPs. Furthermore, various stress resistance assays, including those evaluating oxidative and thermal stress, were conducted. To elucidate the underlying mechanisms, gene expression analysis of key aging-related genes was performed. The results demonstrated that treatment with 25 mg/mL of CCPs extended the lifespan of C. elegans by 13.2%, increased body length and width by 14.8% and 20.6%, respectively, and enhanced head-swing and body-bending frequencies by 66.9% and 80.4%. Lipofuscin content and apoptosis were reduced by 45.9% and 34.1%, respectively. C. elegans treated with 25 mg/mL of CCPs also showed improved stress resistance, a 90.7% increase in glutathione peroxidase (GPX) activity, and a 147.4% increase in glutathione (GSH) content. Transcriptomic analysis showed that CCPs enhanced anti-aging activity by activating the MAPK pathway and inhibiting the IIS pathway, which was associated with protein aggregation. It also reduced lipid synthesis and regulated lipid metabolism through the fat-6 pathway. The results indicated that CCPs could be employed as a valuable ingredient in the food and pharmaceutical fields. Full article

This study explores the potential of ginseng-derived peptides (GPs) as multifunctional bioactive agents for skincare. Unlike previous research into ginseng saponins and polysaccharides, we identified that ginseng extracts containing water-soluble small molecules and polypeptides exhibit potent antioxidant, anti-inflammatory, and anti-aging properties. In vitro assays revealed that ginseng peptide extract (GPE) reduced reactive oxygen species (ROS) and inflammatory cytokines (IL-6, TNF-α, IL-1β) in RAW264.7 macrophages while enhancing collagen synthesis in human skin fibroblasts (HSFs). Validation using 3D epidermal and dermal models further confirmed GPE’s ability to mitigate UV-induced damage, restore skin barrier proteins (filaggrin, loricrin), and increase collagen content. In addition, we screened 19 candidate peptides from ginseng extract using machine learning and prioritized their interaction with skin aging and inflammation-related targets. Three peptides (QEGIYPNNDLYRPK, VDCPTDDATDDYRLK, and ADEVVHHPLDKSSEVE) demonstrated significant collagen-promoting, antioxidant, and anti-inflammatory effects in cellular models. These findings highlight the efficacy of computational approaches in identifying natural bioactive ingredients, positioning ginseng peptides as promising candidates for innovative cosmeceutical formulations targeting inflammaging and skin rejuvenation. Full article

(1) Background: Tendon and ligament injuries are a leading cause of lameness in horses, with significant economic implications. Platelet-rich plasma (PRP) has gained attention for its regenerative potential, but its efficacy remains uncertain due to inconsistent study designs and reporting. (2) Methods: This systematic review, following the PRISMA guidelines, evaluated 22 studies (clinical and experimental) to assess the safety and efficacy of PRP in treating equine tendon and ligament injuries. The risk of bias was analyzed using the ROBINS-I and RoB 2.0 tools. (3) Results: PRP demonstrated a favorable safety profile, with no severe adverse effects reported. Clinical outcomes included improved lameness scores, ultrasonographic tissue organization, and return-to-work rates. However, variability in PRP formulations (e.g., leukocyte-rich vs. leukocyte-reduced) and activation methods (e.g., calcium chloride, thrombin) contributed to inconsistent results. Experimental studies supported PRP’s role in collagen synthesis and neovascularization, but comparative trials with stem cells or other therapies (e.g., extracorporeal shockwave) showed mixed results. The methodological quality of studies varied, with only 27% achieving “good” scores for PRP reporting. (4) Conclusions: PRP is a safe and potentially effective treatment, but its clinical application is hindered by a lack of standardization. Future research should focus on large, randomized controlled trials with uniform PRP protocols, long-term (≥2 years) efficacy assessments, comparative studies with MSC combinations, and cost-effectiveness analyses. Full article