Search Results (10,611)

Platelet-rich fibrin (PRF) has been widely used in regenerative dentistry because of its potential to support tissue regeneration. Recently, modifications in PRF preparation protocols and tube surface characteristics have attracted attention because of their possible influence on fibrin organization and biologic activity. The present in vitro study aimed to evaluate the effects of nano-hydroxyapatite platelet-rich fibrin (HA-PRF) on gingiva-derived mesenchymal stem cells (GMSCs) by comparing it with leukocyte platelet-rich fibrin (L-PRF) and titanium platelet-rich fibrin (T-PRF). Gingival tissue and venous blood samples were obtained from a systemically healthy male volunteer. PRF membranes were prepared using conventional glass tubes, nano-hydroxyapatite-coated tubes, and titanium tubes. GMSCs were isolated, characterized, and cultured with PRF membranes. Cell viability and metabolic activity were evaluated using MTT analysis. Apoptosis and necrosis rates were assessed by Annexin V/PI flow cytometry. VEGF and TGF-β1 release levels were determined by ELISA, whereas IL-1β, IL-6, and TNF-α gene expression levels were analyzed using qRT-PCR. The HA-PRF and L-PRF groups demonstrated higher cell viability values compared with the T-PRF group on day 7. Annexin V/PI analysis revealed no statistically significant differences between the groups in terms of apoptosis and necrosis. Growth factor release and cytokine gene expression profiles demonstrated time-dependent biologic responses in all PRF membranes. Within the limitations of this study, HA-PRF showed no evidence of cytotoxicity and demonstrated biologic responses comparable to those observed with conventional L-PRF. Both HA-PRF and L-PRF generally exhibited more favorable cellular responses than T-PRF under the present experimental conditions. Full article

Adequate placental development and function, prerequisites for the development of a healthy fetus, rely on controlled trophoblast invasion into the decidua and remodeling of the spiral arteries. These tightly regulated processes involve epithelial–mesenchymal transition (EMT) and endovascular differentiation of trophoblast cells. Taxifolin (dihydroquercetin), a natural flavonoid with various pharmacological effects, previously showed cytoprotective, antioxidant, and anti-inflammatory activity on trophoblast cells. Given that the literature indicates that this flavonoid suppresses EMT and can affect angiogenesis across different cell types, we investigated the potential of taxifolin (10 and 100 µM) to modulate invasion and endothelial-like differentiation in human extravillous trophoblast HTR-8/SVneo cells by functional tests. Expression of different molecular markers relevant to these processes was evaluated at the mRNA and protein levels. Our results showed that taxifolin inhibited invasion of HTR-8/SVneo cells, involving downregulation of integrin α5 subunit and modulation of MMP-2 and MMP-9 mRNA expression and secretion. No changes in the concentrations of secreted TIMP-1 and TIMP-2 were observed following taxifolin treatment. Furthermore, downregulation of N-cadherin and vimentin in treated trophoblast cells indicated suppression of EMT. Taxifolin inhibited endothelial-like differentiation of HTR-8/SVneo cells, as evidenced by reduced tube formation and downregulation of VE-cadherin in treated cells. Moreover, expression of TGFB1 was upregulated in treated cells, as were levels of phosphorylated SMAD2/3, indicating involvement of TGF-β signaling in TF-induced effects on trophoblast cells. The in vitro effects of taxifolin on suppression of trophoblast invasion, EMT, and endothelial-like differentiation highlight its potential impact on placental development processes. Full article

Background/Objectives: Non-small cell lung cancer (NSCLC) remains associated with high mortality, frequent late-stage diagnosis, biological heterogeneity, and recurrence after treatment. Although molecular and immunohistochemical biomarkers have transformed treatment selection, there remains a need for accessible, repeatable, and clinically practical circulating biomarkers that may support prognosis and post-treatment monitoring. This review discusses prolactin (PRL) as a candidate supplementary biomarker in NSCLC, with particular emphasis on its biological rationale, potential prognostic relevance, and possible role in personalized risk stratification after systemic therapy. Methods: This narrative review summarizes current evidence on established biomarkers in NSCLC, the physiology and regulation of PRL, PRL/PRLR signaling in cancer biology, mechanisms of PRL dysregulation in lung cancer, and available clinical observations concerning PRL alterations in NSCLC. Particular attention is given to the distinction between prognostic and predictive biomarkers, longitudinal monitoring, pituitary involvement, immune checkpoint inhibitor-related endocrine effects, and biological, pharmacological, and analytical confounders affecting PRL interpretation. Results: Current evidence suggests that PRL may be biologically relevant in NSCLC through its involvement in pathways related to cell proliferation, survival, angiogenesis, invasion, epithelial–mesenchymal transition, immune modulation, and possible therapy resistance. Clinical observations indicate that altered PRL levels may occur in advanced disease, pituitary involvement, systemic inflammation, stress, or during anticancer and supportive treatment. However, PRL lacks cancer specificity and is influenced by multiple confounders, including circadian rhythm, stress, endocrine disorders, macroprolactin, cachexia, medications, and assay variability. Available clinical data remain limited and are largely derived from small studies or case-based evidence. Conclusions: PRL should not currently be considered a standalone diagnostic, predictive, or treatment-selective biomarker in NSCLC. Its most realistic potential role is as a supplementary circulating marker within multimarker prognostic and monitoring models. Prospective validation with standardized sampling, assay procedures, and confounder adjustment is required before clinical implementation. Full article

Acute or chronic rotator cuff tears are major causes of shoulder dysfunction, motivating the development of scaffolds with tailored thickness and mechanics for supraspinatus tendon regeneration. This study aimed to investigate the effect of bilayer poly(butylene adipate-co-terephthalate) (PBAT) scaffold thickness on the tenogenic differentiation of rat adipose mesenchymal stem cells (r-AdMSCs) and supraspinatus tendon regeneration. Aligned fibers with a diameter of approximately 476 nm were deposited onto randomly oriented layers at different times (4 h; 4S, 6 h; 6S, 8 h; 8S), and scaffolds with increasing thicknesses from 441 µm (4S) to 1132 µm (8S) were produced. Mechanical testing showed comparable tensile strength for 4S and 6S (≈1.9–2.0 MPa) and modulus (5.5–7.3 MPa), while 8S exhibited markedly reduced stiffness (0.5 MPa) and hyper elastic deformation. Mechanical performance across degradation conditions remained strongly thickness-dependent: thinner scaffolds retained integrity and strengthened, with modulus increases during hydrolytic and enzymatic degradation, whereas thicker matrices showed limited remodeling and instability. Rat-AdMSCs’ were cultured on the scaffolds for 21 days. Cell-free and cell-laden mechanical responses further reflected thickness effects: cell-free samples stiffened due to media-induced passive matrix tightening, whereas cell-laden scaffolds showed extracellular matrix (ECM)-driven reinforcement, most prominently in 4S, which reached 2.1 MPa tensile strength with improved elasticity and balanced deformation. The 4S scaffold exhibited the highest tensile strength and significantly increased collagen-1 (col1), tenomodulin (tnmd) and scleraxis (scx) expression compared with the other groups. In conclusion, among all groups, 4S scaffolds demonstrated the most favorable mechanical and biological performance, suggesting that scaffold thickness plays a critical role in regulating tendon regeneration and will become even more suitable when matured in bioreactors. Full article

Critical-sized bone defects lack spontaneous healing capacity. While mesenchymal stem cell-derived exosomes (sEVs) are promising osteoinductive agents, their rapid in vivo clearance limits their free-form efficacy. Here, we fabricated a nano-hydroxyapatite/chitosan (nHA/CTS) composite scaffold as a protective, sustained-delivery platform for human umbilical cord blood-derived mesenchymal stem cell exosomes (HUCB-MSCs-exos) to accelerate bone repair. The 3D porous CTS/10% nHA scaffold exhibited excellent cytocompatibility and a degradation rate commensurate with new bone ingrowth. Critically, it enabled a biphasic exosome release profile—an initial burst followed by a 14-day sustained release (89.73% cumulative release). In vitro, HUCB-MSCs-exos significantly promoted the proliferation, migration, and osteogenic differentiation of bone marrow-derived MSCs, as demonstrated by enhanced alkaline phosphatase activity and matrix mineralization. In a rabbit condylar defect model (5 mm diameter), the CTS/10% nHA-exo scaffold achieved a 57.44 ± 8.42% healing rate at two months, nearly two-fold greater than the scaffold-only group (29.33 ± 6.94%). Histological and immunohistochemical analyses at two months confirmed the formation of mature, well-vascularized trabecular bone, accompanied by robust expression of late-stage osteogenic markers (OCN and OPN). These findings demonstrate that the CTS/10% nHA scaffold synergistically integrates osteoconductive structural guidance with exosome-mediated osteoinductive paracrine signaling, providing a compelling and translatable strategy for critical-sized bone-defect management. Full article

Myostatin (MSTN) is a well-established negative regulator of skeletal muscle growth; however, its role in bone metabolism and osteogenic differentiation remains incompletely understood. In this study, untargeted and targeted metabolomic analyses were performed to investigate the metabolic effects of the MSTN^Del73C mutation during osteogenic differentiation of sheep bone marrow mesenchymal stem cells (BMSCs). Metabolomic profiles were analyzed in wild-type and MSTN^Del73C mutant BMSCs at 0, 7, and 14 days of osteogenic induction. During normal osteogenic differentiation, metabolites related to glycerophospholipid metabolism were repeatedly detected among significantly altered features, accompanied by marked increases in multiple lysophospholipid subclasses, including lysophosphatidylcholine (LPC), lysophosphatidylserine (LPS), and lysophosphatidylinositol (LPI). In contrast, MSTN^Del73C mutation was associated with significant reductions in several LPC and LPI species (p < 0.01 or p < 0.001), suggesting altered lipid metabolic profiles during differentiation. Targeted metabolomic validation further confirmed the altered abundance pattern of LPC 18:2. Collectively, these findings suggest that MSTN mutation is closely associated with metabolic remodeling during osteogenic differentiation and suggest potential involvement of glycerophospholipid-related metabolites involved in MSTN-related regulation of sheep BMSC osteogenesis. Full article

Background: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms, accounting for approximately 1–3% of all gastrointestinal tumors, with an annual incidence of 1–2 cases per 100,000 population worldwide. They arise from the interstitial cells of Cajal and are most commonly located in the stomach and small intestine. Methods: We report a case of a 39-year-old man admitted with a preliminary diagnosis of an appendiceal inflammatory mass with suspected abscess formation. Results: The patient presented with right iliac fossa pain, fever, signs of pronounced systemic intoxication and laboratory findings consistent with inflammatory syndrome. Abdominal computed tomography revealed a mass in the right iliac region with infiltration of the surrounding adipose tissue, suggestive of an appendiceal infiltrate. Emergency surgical exploration identified a tumor originating from the cecum. Radical resection of the ileocecal region with side-to-side ileo-ascending anastomosis was performed. Histopathological examination confirmed a spindle-cell variant of GIST. The postoperative course was uneventful. Conclusions: This case highlights the diagnostic challenges of atypically localized GISTs, which may clinically and radiologically mimic inflammatory conditions such as appendiceal infiltrate. Conventional imaging modalities may be insufficient for definitive differential diagnosis. Surgical resection remains the cornerstone of treatment, with histopathological and immunohistochemical evaluation establishing the final diagnosis. Early identification and complete tumor excision are essential for optimizing clinical outcomes and long-term prognosis. Adjuvant therapy with tyrosine kinase inhibitors should be considered based on individual recurrence risk. Full article

Heparanase 1 (HPSE1) is the only mammalian endoglycosidase that cleaves heparan sulfate (HS), a glycosaminoglycan (GAG), and is frequently upregulated in cancers, thereby promoting tumor progression. Despite extensive efforts to develop inhibitors of its HS-degrading activity, its non-enzymatic functions limit therapeutic efficacy and pose a major challenge for therapeutic development. Thus, inhibiting HPSE1 expression is critical for controlling its enzymatic and non-enzymatic functions; however, no FDA-approved inhibitors are currently available. Here, we identify auranofin (AUF), an oral gold-containing drug used to treat rheumatoid arthritis, as a potent inhibitor of HPSE1 promoter activity. High-throughput screening revealed that an atypical protein kinase C (aPKC)–NF-κB signaling axis is a key regulator of HPSE1 expression. Notably, AUF treatment reduced HPSE1 expression and significantly suppressed the invasive capacity of MDA-MB-231 cells in a Transwell migration assay. We then investigated the role of HPSE1 in the invasive activity of MDA-MB-231 cells, which produce higher levels of hyaluronan (HA) and HS than non-invasive cells. Neither HS degradation, HA supplementation in Matrigel during Transwell migration, nor HPSE1 overexpression alone was sufficient to drive invasion, suggesting that invasive capacity depends on mesenchymal features and coordinated induction of HPSE1 and GAGs rather than HS degradation. Collectively, our findings demonstrate that AUF-mediated inhibition of aPKC suppresses HPSE1 expression, thereby inhibiting both its enzymatic and non-enzymatic functions and limiting cancer progression, metastasis, and angiogenesis. These results highlight the therapeutic potential of AUF for targeting HPSE1-driven tumor progression and support its repurposing for cancer treatment. Full article

Intercellular communication is crucial for the coordination of skeletal muscle development. However, the intricate signaling networks that regulate chicken myogenesis are not yet fully elucidated. In this study, we utilized CellChat analysis on single-cell and single-nucleus RNA sequencing data to systematically delineate cell–cell communication patterns across five critical developmental stages of chicken skeletal muscle: embryonic day 4 (E4), day 6 (E6), day 12 (E12), day 18 (E18), and post-hatch day 30 (P30). Our findings indicate that communication architectures are highly stage-specific, with mesenchymal cells acting as the predominant signaling hub during the early embryonic stages (E4–E6), whereas fibro-adipogenic progenitors become the principal communicators during mid-to-late embryogenesis (E12–E18). At E4, the communication network was relatively simple, comprising 51 ligand–receptor pairs primarily involving the neural cell adhesion molecule, slit guidance ligand, and midkine (MK) signaling pathways between myogenic progenitors and mesenchymal cells. By E6, the network had expanded significantly, encompassing 6237 ligand–receptor pairs across 51 signaling pathways, which coincided with the emergence of multiple myogenic lineages. Peak communication complexity was observed at E12, characterized by 11,675 ligand–receptor pairs and 61 signaling pathways, reflecting the secondary wave of myogenesis. Comparative analysis across developmental stages revealed key signaling transitions: the pleiotrophin and MK pathways were predominantly active during the early phase of myogenic commitment (E4–E6), whereas the collagen, laminin, and adhesion G protein-coupled receptor L pathways were more prominent during the secondary myogenesis phase (E6–E12). Notably, a significant shift in communication patterns was observed from E12 to E18, marked by a reduction in developmental pathway signaling and an increase in immune-related communications. By P30, the communication network had stabilized into a homeostatic state, centered on interactions among myofibers, stromal cells, and the vascular system. This comprehensive atlas of intercellular communication offers novel insights into the signaling dynamics underpinning chicken skeletal muscle development. Full article

Head and neck cancer (HNC), particularly oral squamous cell carcinoma (OSCC), remains a major clinical challenge due to its aggressive behavior, high recurrence rates, and frequent resistance to conventional therapies. Natural compounds, especially curcumin and its derivatives, have gained increasing attention as potential anticancer agents due to their ability to target multiple molecular pathways involved in tumor progression. This review critically evaluates the current preclinical and translational evidence supporting curcumin and its derivatives as monotherapeutic agents in HNC, with particular emphasis on oral cancer. We integrate the available evidence to assess the biological rationale, therapeutic potential, and current limitations of curcumin-based approaches. The molecular mechanisms underlying their antitumor activity are discussed, including modulation of EGFR/ERK and PI3K/Akt signaling pathways, inhibition of NF-κB and STAT3 activation, induction of apoptosis, regulation of oxidative stress, and suppression of epithelial–mesenchymal transition and tumor invasiveness. In addition, we address the impact of curcumin on the tumor microenvironment and its role in overcoming intrinsic cellular resistance mechanisms. The review also highlights advances in drug delivery strategies, such as nanoformulations, that are designed to improve curcumin’s bioavailability and therapeutic efficacy. By critically integrating current evidence, this review highlights both the promise and the challenges associated with curcumin-based monotherapy in HNC, emphasizing the need for more robust and clinically relevant studies to support future translation. Full article

Background: Osteoarthritis involves the degeneration of cartilage, subchondral bone, and the synovial membrane, often associated with rotator cuff (RC) tears, causing pain and functional limitations. While non-surgical treatments can provide relief, surgery is sometimes necessary. Autologous adipose-derived mesenchymal stem cells (ADMSCs) have shown promise in tissue repair. Objective: This study compared clinical outcomes between patients treated with arthroscopic RCR alone and those treated with RCR combined with intra-articular AdMSC injection. Methods: This retrospective study included 61 patients. Group A (n = 30) underwent standard RCR, while Group B (n = 31) received RCR combined with intra-articular ADMSC injections. Participants had comparable baseline age, BMI, height, CMS, and VAS scores. Shoulder function was assessed using the Constant–Murley Score, and pain intensity was assessed using the visual analog scale at baseline, 3, 6, and 12 months. Statistical significance was set at p < 0.05. Results: At 3 months, Group B showed lower VAS scores than Group A (13.09 ± 8.34 vs. 25.14 ± 13.57, p < 0.001), while CMSs did not differ significantly (70.55 ± 23.46 vs. 63.01 ± 24.33, p = 0.223). At 6 months, Group B showed better VAS and CMSs than Group A (VAS: 5.31 ± 4.38 vs. 23.74 ± 15.72, p < 0.001; CMS: 83.29 ± 18.98 vs. 65.66 ± 11.58, p < 0.001). At 12 months, Group B maintained better VAS and CMSs than Group A (VAS: 4.45 ± 5.67 vs. 18.34 ± 12.65, p < 0.001; CMS: 85.55 ± 13.12 vs. 66.36 ± 9.38, p < 0.001). Conclusions: In this preliminary retrospective non-randomized cohort, AdMSC use as an adjunct to arthroscopic rotator cuff repair was associated with better pain and functional scores over 12 months. Because of the retrospective design and lack of imaging follow-up, these findings should be interpreted as clinical associations and require confirmation in randomized studies. Full article

This study evaluates the intrinsic osteogenic potential of β-tricalcium phosphate (β-TCP)-containing composite scaffolds (PLCL–TCP, PLGA–TCP, and ZnO–TCP) on chorion-derived mesenchymal stem cells (CMSCs) under non-osteogenic in vitro conditions. CMSCs were cultured on the three biomaterials for 35 days without osteogenic supplements to isolate the material-driven cellular response. Cell viability was assessed via MTT assay, while osteogenesis-associated markers (alkaline phosphatase, type I collagen, and osteocalcin) were quantified using ELISA. Scaffold surface morphology and elemental composition were characterized before and after cultivation utilizing SEM and EDX. All investigated scaffolds supported long-term CMSC viability and induced measurable osteogenic responses. PLCL–TCP demonstrated a consistently strong biological response, characterized by sustained metabolic activity, elevated ALP and COL I production, and increased osteocalcin levels at later stages of cultivation. ZnO–TCP also exhibited favorable osteogenesis-associated responses, particularly with respect to late-stage osteocalcin production, while maintaining high structural stability. In conclusion, β-TCP composites can intrinsically modulate CMSC behavior without biochemical supplements. Osteogenic outcomes depend on a complex interplay of surface chemistry, scaffold architecture, and degradation profiles, with PLCL–TCP demonstrating favorable overall performance among the investigated biomaterials. Full article

Immunotherapy has transformed cancer treatment; however, clinical benefit remains limited to a subset of patients, underscoring the need for robust biomarkers that capture tumor-immune interactions across cancer types. In this study, we performed a comprehensive pan-cancer, multi-omics characterization of the immune checkpoint–related molecules CD70, CD80, and TIGIT to evaluate their diagnostic, prognostic, and immunological relevance. Using integrative analyses of transcriptomic, epigenomic, genomic, pharmacogenomic, and single-cell RNA-sequencing data from The Cancer Genome Atlas and complementary resources, we assessed expression patterns, DNA methylation, somatic mutations, copy number alterations, immune infiltration, tumor stemness, and drug sensitivity. CD70, CD80, and TIGIT were broadly dysregulated across multiple malignancies, with coordinated overexpression particularly evident in kidney renal clear-cell carcinoma. Elevated expression of these immune checkpoints was associated with advanced tumor stage, aggressive molecular subtypes, and unfavorable survival outcomes in selected cancers, including uveal melanoma and renal malignancies. Functional analyses revealed significant associations between checkpoint expression and key oncogenic pathways, including epithelial–mesenchymal transition, apoptosis, and hormone receptor signaling, suggesting links with tumor progression and immune activation states. Immune deconvolution analyses indicated that TIGIT expression is associated with a T-cell–inflamed microenvironment and reduced neutrophil infiltration, while CD80 exhibited methylation-dependent associations with immune cell composition. Genomic and epigenetic alterations were found to correlate with checkpoint expression patterns and immune phenotypes across tumor types. Pharmacogenomic profiling identified associations between checkpoint expression and sensitivity to multiple anticancer agents; however, these findings are based on cell line datasets and should be considered predictive. Single-cell transcriptomic analyses further resolved cell-type–specific expression patterns, distinguishing tumor-intrinsic from immune-restricted expression profiles. Collectively, our findings establish CD70, CD80, and TIGIT as integrative biomarkers of tumor progression, immune contexture, and therapeutic response, providing a rationale for their clinical exploitation in precision immuno-oncology. Full article

This study elucidates the multi-targeted antineoplastic mechanisms of Parkia speciosa empty pod extract (PSET) against HCT-116 and HT-29 colorectal cancer (CRC) cells through integrated transcriptomic and proteomic analyses. Phytochemical profiling indicates that PSET is rich in bioactive metabolites, notably quercetin, rutin, and pyrogallol, which orchestrate its profound ability to inhibit tumor proliferation, migration, and invasion. Transcriptomic data revealed that PSET profoundly suppresses the oncogenic Wnt/β-catenin signaling axis while simultaneously activating p53-mediated cell cycle arrest. Complementary proteomic profiling uncovered critical metabolic vulnerabilities, demonstrating that PSET abrogates the Warburg effect by disrupting key glycolytic enzymes (e.g., ENO1, GAPDH, LDHA), thereby inducing metabolic starvation. Furthermore, the extract precipitated a catastrophic collapse of the cytoskeletal architecture and downregulated epithelial–mesenchymal transition (EMT) markers, effectively paralyzing the cells’ metastatic machinery. The integrated transcriptomic and proteomic signatures also highlighted an irrecoverable state of cellular stress, characterized by an overwhelming unfolded protein response and dysregulated RNA splicing, ultimately driving the cells toward apoptosis. In conclusion, this integrated omics approach provides robust molecular validation that PSET systemically dismantles colorectal cancer survival networks, highlighting its strong potential as a natural, multi-targeted therapeutic agent. Full article

Background: Osteochondral lesions of the talus (OLT) remain a challenging condition due to the limited regenerative potential of articular cartilage. Conventional bone marrow stimulation (BMS) techniques often result in fibrocartilage formation with inferior biomechanical properties. This study aimed to evaluate the safety and preliminary clinical efficacy of an arthroscopically assisted, single-stage injection of a heparin-conjugated fibrin hydrogel (HCFH) for OLT treatment. Methods: Twelve patients with symptomatic OLT underwent arthroscopic debridement, microfracturing, and HCFH injection containing autologous mesenchymal stromal cells (MSCs) and growth factors. Safety was assessed through systematic monitoring of adverse events (graded according to Common Terminology Criteria for Adverse Events criteria), wound healing, and serial laboratory inflammatory markers (leukocytes, erythrocyte sedimentation rate, C-reactive protein) during early and late follow-up. Clinical outcomes were evaluated using the Visual Analog Scale (VAS) and American Orthopedic Foot and Ankle Society score (AOFAS) preoperatively and at 6 and 12 months. Morphological assessment was performed using magnetic resonance imaging (MRI) with the modified Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scoring system, evaluated independently by two blinded musculoskeletal radiologists. Results: No serious adverse events (Grade III–IV) were observed during the 12-month follow-up. All adverse events were mild (Grade I) and self-limited. A transient postoperative elevation in inflammatory markers was observed, returning to clinically acceptable levels by day 14. Significant improvements were noted in pain (VAS decreased from 6.0 to 2.0) and ankle function (AOFAS increased from 70.0 to 90.6) (p < 0.001). MRI demonstrated progressive morphological improvement, with the MOCART score increasing from 34.16 ± 17.1 at 6 months to 75 ± 5.43 at 12 months (p < 0.001). This increase corresponded with imaging features consistent with tissue maturation over time. The favorable MOCART outcomes observed in this study may be explained by the regenerative properties of heparin-conjugated fibrin hydrogels; however, larger randomized controlled trials with longer follow-up are needed to confirm the durability of the regenerated tissue. Interobserver agreement was substantial to almost perfect for MOCART scoring (κ = 0.68–0.84), with perfect agreement observed for surface assessment, bony defect/overgrowth, and cysts. Conclusions: Within the limitations of this study, single-stage HCFH injection demonstrated an acceptable safety profile and favorable preliminary clinical and radiological outcomes at 12 months. These findings suggest potential regenerative capability; however, controlled studies with larger cohorts and longer follow-up are required to determine comparative efficacy and long-term durability. Full article