Search Results (428)

In osteopetrotic mice with homozygous inactivating mutations in the colony stimulating factor 1 (Csf1^op/op) or its receptor (Csf1r^−/−) gene, teeth fail to erupt due to severe reduction in osteoclastogenesis. Dental abnormalities have been described in the unerupted teeth of these models, but it remains unclear whether these defects arise from direct roles of CSF1R in odontogenesis or indirectly from impaired bone remodeling associated with failed eruption. Here, we examined the spatiotemporal expression of CSF1R during tooth development and inhibited CSF1R pharmacologically in utero using PLX5622 during early stages of tooth morphogenesis. Teeth and surrounding bone were analyzed at embryonic and postnatal stages using histology and high-resolution micro-computed tomography. Embryonic CSF1R inhibition resulted in reproducible abnormalities in incisor and molar morphology that were evident before and after birth and were associated with loss of normal bone remodeling at the tooth–bone interface. In contrast, postnatal CSF1R inhibition did not affect the structure or continuous growth of adult incisors. Together, these findings demonstrate a temporally restricted, indirect role for CSF1R in odontogenesis that is independent of tooth eruption and associated with remodeling of the bony crypts surrounding developing teeth by CSF1R-dependent cells. Full article

Background and Aims: Anemia is seen in nearly >70% of patients with cirrhosis and is often non-responsive to nutritional supplements; therefore, we assessed the erythropoiesis and associated alteration in bone marrow (BM). Methods: It is a cross-sectional study. Flow cytometry was performed to assess the hematopoietic stem cells (HSCs) and erythroid population of 60 patients with cirrhosis compared with patients with 7 non-cirrhotic portal fibrosis (NCPF) and 3 controls. Proteomics were performed of the pure CD71 erythroid population taken from patients with cirrhosis to decipher the internal abnormalities supported by validation experiments. Real Time PCR, colony assay and heme quantification, cytokine array, and ELISA were performed to assess erythropoietic stimulating agents (ESA), inflammatory cytokines, and growth factors as an external factor affecting erythropoiesis. Results: We found a decrease in intermediate erythroid progenitors [IEPs; CD71+ CD235a+], conversely early erythroid precursors [EEP; CD71+ CD235a−] and late erythroid progenitors [LEP; CD71− CD235a+] were increased (p < 0.05) in cirrhotic and NCPF as compared to control. However, unlike NCPF, cirrhosis exhibited decreased CD71+ transferrin receptor (TfR1) expression over erythroid cells and increased immature erythrocytes (p < 0.05) in peripheral circulation. In vitro culture of erythroid precursors showed impaired differentiation and maturation that was confirmed by the reduced (p < 0.05) number of erythroid colonies (BFU-E). Proteomics analysis showed downregulated proteins associated with hemoglobin synthesis, ROS detoxification, translation, and mitochondrial activity. Furthermore, we found an altered expression of genes related to erythropoiesis and hemoglobin synthesis and increase (p < 0.05) in inflammatory cytokines such as IL-5, TRAIL-R2, TGF-α, and TGF-β in BM. Conclusions: This study suggests that the dysregulated erythropoiesis observed in patients with cirrhosis having anemia is maintained despite adequate nutrition. Full article

Background/Objectives: A blunted growth hormone (GH) response in stimulation tests (GHSTs) in obese patients is well documented, with less evidence for insulin-like growth factor-1 (IGF-1) concentrations. The aim of this study was to assess the relationships between nutritional status, GH peak in GHST, and IGF-1 concentrations, and to develop machine learning prediction models of GH deficiency (GHD) in children with short stature. Methods: A case–control study included 1592 children with short stature, whose height, weight, body mass index (BMI), GH peak in two GHSTs, IGF-1 concentration and bone age (BA) were assessed. The cut-off of GH peak in two GHSTs between GHD and idiopathic short stature (ISS) was 10.0 µg/L; additionally, a lower cut-off of 7.0 µg/L was used in repeated analysis. Univariate statistical analyses and classification models were used to identify variables related to the normal and subnormal results of GHST. Results: Depending on the cut-off of GH peak (10.0 vs. 7.0 µg/L), GHD was diagnosed in 604 vs. 279 patients (37.9% vs. 17.5%). Children with GHD had significantly lower (p < 0.001) BMI SDS and IGF-1 SDS than ones with ISS for both cut-offs of GH peak. Overnutrition was associated with the lowest GH peak but the highest IGF-1 SDS; the opposite results were observed in undernutrition. A decision tree predicted GHD in 156 patients, in 149 based on BMI SDS > 0.91. A Naïve Bayes classifier predicted GHD in 118 cases, with BMI SDS and IGF-1 SDS being the only significant variables. The best multilayer perceptron (MLP) neural network predicted GHD in 310 patients, while a logistic regression model did so in 269 patients. Conclusions: Interpretation of GHST should include the patient’s nutritional status in order to avoid overdiagnosis of GHD in overweight and obese children. Full article

Bone tissue plays a vital role in the human body and possesses intrinsic self-repair mechanisms; however, large defects or pathological fractures may exceed its natural healing capacity. Bone tissue engineering provides promising strategies to restore bone integrity through the use of scaffolds, growth factors, and stem cells. While calcium phosphate (CaP)-based ceramics, such as hydroxyapatite (HAp) and tricalcium phosphate (TCP), represent the current benchmark, their limitations, including slow degradation (HAp) and limited osteoinductivity (TCP), have driven the development of alternative biomaterials. In this context, magnesium phosphate (MgP)-based materials have gained increasing attention due to their tunable resorption rate, improved biodegradability, and ability to stimulate osteogenesis and angiogenesis through the release of magnesium (Mg²⁺) ions. This study reports on composite scaffolds based on electrospun poly(ε-caprolactone) (PCL) fibres coated with MgP layers doped with lithium (Li) and zinc (Zn), designed to mimic the nanofibrous architecture of the extracellular matrix. Lithium and zinc were selected due to their known ability to modulate cellular response, with lithium promoting osteogenic activity and zinc contributing to improved cell proliferation and antibacterial potential. The phosphate phases obtained by coprecipitation were deposited onto the PCL fibres using Matrix-Assisted Pulsed Laser Evaporation (MAPLE), enabling controlled surface functionalization. Following thermal treatment, the formation of the crystalline magnesium pyrophosphate (Mg₂P₂O₇) phase was confirmed by chemical and structural characterization. The combination of a slowly degrading PCL matrix, providing sustained structural support, and a bioactive MgP coating, enabling rapid and controlled ion release, results in improved scaffold performance in terms of biocompatibility, biodegradability, and bioactivity. While the slow degradation rate of PCL ensures mechanical stability over an extended period, the surface-deposited MgP phase allows immediate interaction with the biological environment, facilitating faster ion release and enhancing cell–material interactions. These findings highlight the potential of the developed composites as promising candidates for trabecular bone regeneration and as viable alternatives to conventional CaP-based scaffolds in regenerative medicine. Full article

Heterotopic ossification (HO), the pathological formation of mature bone in non-skeletal soft tissues (e.g., muscles, tendons), severely impairs patient mobility and quality of life. Despite decades of research, systematic analysis of signaling networks across HO subtypes (acquired traumatic HO, hereditary Fibrodysplasia Ossificans Progressiva (FOP), Progressive Osseous Heteroplasia (POH)) remains insufficient, and clinical therapies suffer from high recurrence and severe side effects. This review synthesizes recent advances in HO pathogenesis: FOP involves gain-of-function activin A receptor type I (ACVR1) mutations (mostly R206H), disrupting bone morphogenetic protein (BMP)/Activin A signaling; POH arises from paternal guanine nucleotide-binding protein, alpha-stimulating activity polypeptide (GNAS) loss-of-function mutations, derepressing Hedgehog signaling via reduced cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) activity; tHO features trauma-induced inflammation/hypoxia activating BMP/transforming growth factor–beta (TGF-β) pathways. Key signaling crosstalk (e.g., BMP-Yes-associated protein (YAP)-Indian hedgehog (IHH)) is integrated, and novel therapies (ACVR1 inhibitors, Activin A antibodies, retinoic acid receptor gamma (RARγ) agonists, adeno-associated virus (AAV)-mediated ACVR1 silencing) are highlighted, with emphasis on subtype-specific efficacy. A stratified, mechanism-based HO management framework is proposed, aiming to accelerate precision therapy development and advance understanding of aberrant tissue regeneration. Full article

Androgens regulate skeletal muscle, bone, erythropoiesis, and male reproductive function via the androgen receptor (AR), a ligand-dependent transcription factor. Pharmacologic modulation of AR has been pursued for clinical and non-medical purposes. Anabolic androgenic steroids (AAS), synthetic testosterone derivatives, act as full AR agonists, broadly activating multiple tissues. While effective in promoting muscle growth and strength, AAS cause well-known adverse effects, including hypothalamic–pituitary–gonadal (HPG) axis suppression, dyslipidemia, hepatotoxicity, cardiovascular disease, tendon injury, and neuropsychiatric disturbances. Selective androgen receptor modulators (SARMs) aim to stimulate AR in muscle and bone while minimizing androgenic effects in prostate and skin. They induce ligand-specific AR conformations, altering coactivator and corepressor recruitment, and avoiding metabolism by 5α-reductase or aromatase. Preclinical studies show favorable anabolic-to-androgenic ratios, but clinical translation is limited. Early human trials report modest lean mass gains, variable functional outcomes, and dose-dependent testosterone suppression. Emerging evidence also suggests cardiotoxicity, tendon injury, and liver toxicity, though long-term effects are unclear. Pharmacokinetically, SARMs have predictable oral absorption and moderate half-lives, enabling once-daily dosing, unlike AAS. This review compares AAS and SARMs in molecular mechanisms, pharmacokinetics, and safety. While SARMs offer partial tissue selectivity and reduced adverse effects, risks remain, and long-term safety is uncertain. Regulatory oversight is limited, and non-medical use is rising. Preclinical and clinical studies are needed to clarify whether SARMs can separate anabolic benefits from androgenic toxicity and inform safe clinical application. Full article

This study aims to evaluate the therapeutic efficacy of emodin (EMO) in rheumatoid arthritis (RA) and to verify whether its underlying mechanism involves the blockade of pathological angiogenesis via the inhibition of the nuclear factor-kappa B (NF-κB)/hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling axis. Bovine type II collagen-induced arthritis (CIA) mouse models and lipopolysaccharide (LPS)-stimulated EA.hy926 endothelial cells were utilized in this study. The effects of EMO on joint pathological alterations, the expression of NF-κB/HIF-1α/VEGF axis proteins, inflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β)), and angiogenic capacity were assessed using histopathological analysis, Western blotting, immunohistochemistry (IHC), immunofluorescence, and tube formation assays. Furthermore, small interfering RNA (siRNA) interference targeting key molecules was employed to validate the molecular mechanisms underlying the therapeutic effects of EMO. In the CIA model group, the ankle joints of mice exhibited pronounced inflammatory infiltration, synovial hyperplasia, and bone destruction. Compared with the model group, both the EMO and methotrexate (MTX) treatment groups demonstrated attenuated synovial hyperplasia and cartilage destruction, along with significantly downregulated expression levels of key NF-κB pathway proteins, HIF-1α, and VEGF in joint tissues (p < 0.001). In vitro experiments revealed that EMO treatment significantly reduced the LPS-induced secretion of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) (p < 0.001), and decreased both the number and total length of tubular structures formed by endothelial cells compared to the control (p < 0.001). Notably, siRNA-mediated knockdown of p65 resulted in decreased intracellular protein levels of HIF-1α and VEGF, accompanied by a significant reduction in tube formation (p < 0.001). This study demonstrates that EMO alleviates pathological damage in RA by inhibiting the activation of the NF-κB signaling pathway, which subsequently downregulates pathological angiogenesis and inflammatory responses mediated by the HIF-1α/VEGF axis. These findings provide a robust experimental basis for the potential application of EMO as a therapeutic agent for RA. Full article

Sorghum is known for its anti-cancer, anti-inflammatory, and antioxidant properties, but its effect on cell growth is not well understood. First, the cytotoxicity of various sorghum extract (SE) concentrations was evaluated in C2C12 (murine myoblasts) and C3H10T1/2 (murine embryonic fibroblasts). The extent of DNA damage was then assessed, and the activation of the JAK2/STAT5b and IGF-1 pathways was observed. Studies on the transcriptional regulatory function of STAT5b revealed that SE increased STAT5b/DNA binding and transcriptional promoter activity. Consequently, STAT5b upregulation led to the increased expression of IGF-1. Moreover, other factors, such as growth hormone receptor and bone morphogenetic protein 7, were also upregulated. The results of these experiments suggest that sorghum may enhance muscle recovery or promote growth factors by stimulating the JAK2/STAT5b and IGF-1 pathways. Therefore, sorghum is expected to be an effective functional food for bone growth and muscle recovery, without inducing adverse side effects. Full article

Bone tissue regeneration represents a complex biological process regulated by mechanical, biochemical, and cellular interactions. It remains a major challenge in regenerative medicine due to the limited self-healing capacity of large or complex bone defects. Recent advances have highlighted the pivotal role of biophysical stimuli, such as mechanical loading, electromagnetic fields, ultrasound, and photobiomodulation, in promoting osteogenic differentiation and tissue remodeling. At the same time, bioactive substances, including growth factors, peptides delivered primarily via extracellular vesicles, and biomaterial-based delivery systems, have shown a potential role in enhancing cellular responses and modulating the microenvironment to promote regeneration. This review aims to provide a comprehensive overview of the latest progress in understanding how biophysical and bioactive stimuli converge to regulate bone regeneration and to consider their synergistic approaches that integrate physical stimulation with the controlled release of bioactive molecules. These combined strategies are promising to improve tissue integration and reduce healing times and complications, representing a future research direction. Full article

Osteoporosis is characterized by reductions in bone mineral density (BMD) and bone quality. While gut-derived signaling has been increasingly studied in relation to BMD, its contribution to molecular factors associated with bone quality remains less defined. Here, we investigated whether a heat-inactivated, freeze-dried, non-viable preparation of Levilactobacillus brevis AS-1 modulates intestinal epithelial-like cells and thereby promotes lysyl oxidase (LOX), a key enzyme involved in collagen cross-linking. Caco-2 cells were treated using 1 mM sodium butyrate and subsequently stimulated with 100 μg/mL L. brevis AS-1. Supernatants were collected and applied to MG63 cells. Cytokine mRNA expression in Caco-2 cells and LOX responses in MG63 cells were analyzed by qRT-PCR, and bone morphogenetic protein (BMP-1) and transforming growth factor-β (TGF-β)1 protein levels in the supernatant were measured by ELISA. L. brevis AS-1 stimulation up-regulated BMP-1 and TGF-β1 mRNA expression in SB-treated Caco-2 cells and increased BMP-1 protein secretion into the supernatant. LOX mRNA expression and total LOX activity were increased in MG63 cells treated with the conditioned supernatant, and inhibition of BMP-1/procollagen C-proteinase activity (UK383367) attenuated LOX mRNA induction. Collectively, these results suggest that L. brevis AS-1 stimulates intestinal epithelial-like cells to secrete BMP-1, which in turn promotes LOX mRNA expression in osteoblast precursor cells. This in vitro mechanism supports the concept of gut–bone crosstalk regulating molecular factors associated with bone quality. Full article

Background: Glucocorticoids (GCs) are a key pathogenic factor in steroid-induced avascular necrosis of the femoral head (SANFH). GCs can directly damage bone microvascular endothelial cells (BMECs), leading to impaired intraosseous blood supply. Recent studies suggest the Hippo signaling pathway may be involved in the pathogenesis of SANFH; however, its role in vascular endothelial repair and angiogenesis remains unclear. This study aims to investigate the therapeutic effects of human umbilical cord mesenchymal stem cells (hUC-MSCs) on SANFH, with a particular focus on their protective or reparative mechanisms on BMECs. Methods: In vivo, a SANFH mouse model is established and divided into NC, MPS, and hUC-MSCs groups, followed by Micro-CT imagin, hematoxylin and eosin (HE) staining and immunohistochemistry (IHC) (n = 8 per group). In vitro, BMECs are divided into NC, dexamethasone (Dex), hUC-MSCs, and Fer-1 groups to analyze cellular biological behaviors. Target protein expression is assessed using Western blotting and immunofluorescence microscopy. Ferroptosis-related markers are detected via biochemical assays. Mitochondrial ultrastructural changes are observed using transmission electron microscopy. Results: In vivo, the MPS group exhibited significant bone cavitation, sparse trabeculae, and disrupted trabecular architecture in the femoral head. The hUC-MSCs group showed marked improvement in bone microstructure, HE staining showed a significant decrease in the empty lacunae rate in the femoral head, and IHC results revealed markedly increased expression of cluster of differentiation 31 (CD31) and vascular endothelial growth factor (VEGF). In vitro, Dex stimulation suppressed BMECs proliferation. In Dex-treated cells, levels of intracellular reactive oxygen species (ROS), lipid peroxides, ferrous ion (Fe²⁺), malondialdehyde (MDA), acyl-CoA synthetase long chain family member 4 (ACSL4) and nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) were all increased, while expression of glutathione (GSH) and glutathione Peroxidase 4 (GPX4) was reduced. Transmission electron microscopy revealed plasma membrane rupture and reduction or loss of mitochondrial cristae. Furthermore, Dex promoted Hippo-mediated phosphorylation of Yes-associated protein (YAP)/Transcriptional coactivator with PDZ-binding motif (TAZ), upregulated NOX4 expression, and suppressed CD31 and VEGF expression. Following hUC-MSCs treatment, BMECs demonstrated enhanced proliferation, migration, and tube-forming capacity. Cellular GSH and GPX4 levels increased, antioxidant capacity was restored, peroxide accumulation decreased, and cells were protected from ferroptosis-effects comparable to those in the Fer-1 group. Additionally, hUC-MSCs inhibited YAP/TAZ phosphorylation and promoted elevated expression of CD31 and VEGF. Conclusions: These findings suggest that hUC-MSCs may attenuate Dex-induced ferroptosis in BMECs, enhance BMEC migration and angiogenesis, and improve femoral head microstructure in SANFH through modulation of the Hippo-YAP/TAZ signaling pathway. This study provides novel insights into the therapeutic potential of hUC-MSCs for SANFH. Full article

Leukopenia remains a major clinical challenge associated with infectious diseases, oncological therapies, autoimmune disorders, and metabolic and iatrogenic conditions. Insufficient leukopoiesis not only increases susceptibility to infections but also limits the intensity and continuity of anticancer and immunosuppressive treatments. Targeted stimulation of leukopoiesis therefore represents a critical therapeutic strategy in modern biomedicine. This narrative review summarizes pharmacological and biotechnological approaches to leukopoiesis stimulation based on an analysis of peer-reviewed literature from major biomedical databases. Emphasis was placed on molecular mechanisms of action, clinical positioning, and translational potential of leukopoiesis-modulating agents. Current leukopoiesis-stimulating strategies encompass cytokine-based therapies, bone marrow-derived peptides, thymic and microbial immunomodulators, nucleic acid-based agents, plant-derived compounds, and chemically synthesized small molecules. Classical colony-stimulating factors remain the cornerstone of clinical practice; however, their limitations, including adverse effects and restricted spectrum of action, have driven the development of alternative approaches. Emerging strategies increasingly target specific regulatory nodes of hematopoiesis, including bone marrow stromal interactions, transcription factor signaling, chemokine receptor pathways, and immune cell differentiation programs. Advances in the understanding of leukopoiesis regulation have expanded therapeutic opportunities beyond conventional growth factor administration. Pharmacological and biotechnological targeting of leukopoiesis holds promise for improving clinical outcomes in patients with leukopenia of diverse etiologies. Future progress in this field will depend on the integration of mechanistic insights with clinical evidence to enable more selective, effective, and safer leukopoiesis-stimulating therapies. Full article

Advances in regenerative medicine have positioned platelets and their derivatives—including platelet-rich plasma, platelet-rich fibrin, platelet lysate, extracellular vesicles, and purified growth factors—as promising interventions specifically for skin and bone aging, two clinically accessible tissues with robust preclinical and clinical evidence for platelet-derived component-based rejuvenation and regeneration. Because much of the available evidence comes from injury models or age-associated inflammatory/degenerative diseases, we explicitly distinguish pathology-targeted inflammation resolution/repair from rejuvenation under physiological aging. This review summarizes the composition and core bioactivities of platelet-derived products and delineates their putative anti-aging mechanisms, encompassing proangiogenic signaling, immunomodulation, attenuation of oxidative stress, regulation of extracellular matrix turnover, and stimulation of osteogenesis. We further evaluate emerging applications that expand therapeutic performance, such as platelet-mimetic delivery vehicles, engineered and sustained-release formulations, and targeted use of subcellular structures. Evidence from recent preclinical and clinical studies indicates favorable safety profiles and signals of efficacy across cutaneous rejuvenation and skeletal regeneration, while underscoring persistent challenges related to product standardization, dosing, and outcome measures. Collectively, platelet-based therapeutics represent a versatile platform with broad applicability to anti-aging interventions in skin and bone and strong potential for translation through continued bioengineering and clinical validation. However, because most available evidence comes from injury models or age-associated diseases (e.g., photoaging, chronic wounds, osteoarthritis, osteoporosis), direct extrapolation to physiological aging is limited; throughout, we explicitly contrast these contexts, specify their indication-specific endpoints, and summarize the main translational limitations. Full article

Research in implant dentistry has predominantly focused on bone regeneration, osseous volume maintenance, and successful osseointegration. However, soft tissue healing, which influences implant functional sealing, long-term stability, and esthetic integration, remains underexplored. This study investigated the effects of three xenogenic bone substitutes on gingival healing in vitro. Three experimental groups were established using extracts from bone substitutes diffusing through the OsteoBiol^® Evolution collagen membrane: two collagenated substitutes, OsteoBiol^® Gen-Os^® (Gen-Os) and OsteoBiol^® GTO^® (GTO), and one inorganic substitute, Bio-Oss^® (Bio-Oss). The substitutes were prepared in test tubes, and the extracts diffusing through the collagen membrane were used to evaluate human gingival cell (hGC) proliferation (MTT assay), migration (scratch assay), and growth factor release (ELISA). Angiogenic potential was assessed by endothelial cell proliferation, recruitment (Boyden chambers), and organization (Matrigel^® assays). The indirect interaction between stimulated gingival cells and human bone marrow mesenchymal stem cells (hMSC) was investigated by analyzing hMSC recruitment and osteogenic BMP-2 secretion. Collagenated GTO and Gen-Os significantly enhanced hGC proliferation and migration in the scratch assay, with 1.8-fold and 1.6-fold increases, respectively, compared to control. All three substitutes enhanced neoangiogenesis in vitro. VEGF and FGF-2 secretion was significantly higher with GTO, showing 5-fold and 5.7-fold increases, respectively, resulting in a 3.7-fold increase in tube formation compared to control. Collagenated materials promoted hMSC recruitment, whereas BMP-2 secretion was not affected by any material. The observed effects were higher with the collagenated Gen-Os and GTO, with 2.5-fold and 2.8-fold increases, respectively, than with the non-collagenated Bio-Oss, which showed a 1.5-fold increase. These findings demonstrate that collagenated bone substitutes enhance gingival healing and angiogenic potential through barrier membranes and confirm that stimulated gingival cells indirectly promote hMSC recruitment, indicating that bone substitute effects extend beyond bone regeneration to include soft tissue healing and inter-tissue communication. Full article

Exosomes are small extracellular vesicles that package DNA fragments, several classes of RNA, lipids, and proteins, and are now regarded as active messengers between cells rather than as cellular debris. This narrative review synthesizes dermatologic and related regenerative applications reported between 2020 and 2025, drawing on PubMed and Scopus searches. In skin, exosomes regulate inflammation, angiogenesis, matrix remodeling, pigmentation, and hair cycling. Preclinical models show faster wound closure, improved scar architecture, attenuation of photoaging changes, and stimulation of hair growth, with additional signals in inflammatory dermatoses and fungal skin disease. Early human studies in wound care, rejuvenation, scars, and alopecia suggest acceptable safety and a recurring pattern of benefit when exosomes are used as adjuncts to microneedling, lasers, or standard dressings, although products, dosing, and outcome measures remain heterogeneous. Beyond dermatology, early work in osteoarticular and soft tissue repair points toward meaningful regenerative potential, but clinical programs are still at an early stage. In practice, exosomes are being positioned as acellular alternatives or add-ons to platelet-rich plasma, bone marrow aspirate concentrate, and conventional topicals and as emerging carriers for small molecules and biologics. Key limitations include low yields, product and cargo heterogeneity, lack of agreed quality and potency metrics, and uncertain regulatory status. Whether exosomes remain boutique adjuncts or become part of standard dermatologic and musculoskeletal practice will depend on what happens next: consistent manufacturing, agreed-upon characterization panels, meaningful potency assays, robust pharmacokinetic and biodistribution data, and comparative trials that track outcomes and safety over years rather than weeks. Full article