Search Results (544)

Background and Objectives: Shoulder disorders—including rotator cuff disease, glenohumeral osteoarthritis (GH OA), and adhesive capsulitis—are among the most prevalent musculoskeletal conditions and are frequently refractory to conservative management. Platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) have attracted increasing clinical interest as regenerative alternatives to corticosteroid injection, but a comparative appraisal of these two principal biologics across the full spectrum of shoulder pathology is lacking. Materials and Methods: This narrative review is based on structured searches of MEDLINE, Embase, Cochrane CENTRAL, and Scopus for clinical studies (randomized controlled trials [RCTs], comparative studies, and prospective series) and evidence syntheses evaluating PRP or BMAC in shoulder disorders. Studies were synthesized narratively by biologic type and disorder; no formal systematic-review or scoping-review reporting protocol was applied. Current society guidelines and consensus statements were additionally examined to position each biologic, and PRP formulation subgroups (leukocyte-rich versus leukocyte-poor) were considered. Results: PRP has the larger shoulder-specific evidence base, supported by several RCTs and meta-analyses in rotator cuff tendinopathy and in adhesive capsulitis; however, results are heterogeneous, effect sizes are generally modest, and some trials show no advantage over saline or corticosteroid. BMAC shoulder evidence is sparse and is strongest as a biological augment to rotator cuff repair (supported chiefly by a case-controlled study) rather than as a standalone injection; standalone shoulder BMAC RCTs are essentially absent. No published RCT directly compares PRP with BMAC for a shoulder disorder; the only direct randomized head-to-head comparison available is in knee osteoarthritis, where the two were reported to be equivalent at two years. Where PRP formulation was examined, leukocyte-poor preparations were associated with better structural and pain outcomes and leukocyte-rich preparations with functional gains in the surgical setting; current society guidance (e.g., the 2025 American Academy of Orthopaedic Surgeons [AAOS] rotator cuff guideline) does not endorse routine PRP use, and BMAC is not yet incorporated into shoulder guideline recommendations. Conclusions: PRP rests on a larger but still heterogeneous evidence base for shoulder disorders, whereas BMAC is biologically promising but clinically under-evidenced in the shoulder. Neither biologic is established as superior. Standardized, shoulder-specific head-to-head RCTs—incorporating biologic characterization, structural (imaging) outcomes, and longer follow-up—represent the most important research priority in this field. Full article

Adhesive capsulitis (AC) is a common fibroinflammatory shoulder disorder, affecting 2–5% of the general population and up to 20% of people with diabetes mellitus. Although historically considered self-limiting, the course frequently exceeds two years and imposes a substantial functional burden. Intra-articular corticosteroids remain the predominant first-line option, but their benefit is often short-lived and is offset by transient hyperglycemia in diabetic patients, potential tissue toxicity with repeated use, and limited durability. These limitations have prompted interest in non-steroidal, ultrasound-guided alternatives. This narrative review appraises two complementary strategies: ultrasound-guided regenerative injectates (hyaluronic acid, hypertonic dextrose prolotherapy, and platelet-rich plasma) and ultrasound-guided perineural hydrodissection of the suprascapular, axillary, and subscapular nerves. We summarize comparative efficacy with corticosteroids, durability, injection anatomy, and the subgroups most likely to benefit. We then propose—explicitly as a clinically defensible framework rather than a validated guideline—a phase-specific paradigm in which a timely non-steroidal injection provides early pain control while stage-appropriate rehabilitation drives functional recovery. The hypothesis that this sequence may compress the symptomatic course to approximately three to six months is supported by preliminary evidence and requires prospective validation. Because no head-to-head trial has compared the proposed paradigm with the corticosteroid-first standard, these recommendations warrant corresponding caution. Full article

Hypogonadism is increasingly recognized as an independent cardiovascular risk factor, with testosterone deficiency associated with endothelial dysfunction, increased thrombotic risk, and adverse cardiovascular outcomes. Circulating biomarkers provide valuable insights into the vascular health status of hypogonadal men and the cardiovascular effects of testosterone replacement therapy (TRT). This comprehensive review examines the molecular basis of testosterone action on the cardiovascular system and synthesizes evidence on circulating cardiovascular biomarkers in hypogonadism, including endothelial progenitor cells (EPCs), endothelial microparticles (EMPs), platelet markers, endothelial activators, adhesion molecules, and inflammatory/oxidative stress markers. We also compare the cardiovascular safety profiles of transdermal versus intramuscular testosterone formulations. Hypogonadal men exhibit reduced circulating EPCs, elevated EMPs, increased platelet reactivity, higher levels of endothelial activators (ICAM-1, VCAM-1, E-selectin, von Willebrand factor, endothelin-1, ADMA), and increased inflammatory markers (hsCRP, IL-6, TNF-α). TRT improves most of these biomarkers through androgen receptor (AR)-dependent and AR-independent mechanisms involving PI3K/Akt/eNOS signaling, VEGF upregulation, CXCL12/CXCR4 axis modulation, and NF-κB pathway suppression. Current evidence suggests that transdermal testosterone formulations may offer advantages regarding hematological safety and more stable testosterone exposure; however, definitive evidence demonstrating superior cardiovascular outcomes compared with intramuscular formulations remains limited. Circulating cardiovascular biomarkers are significantly altered in hypogonadism and improve with TRT. Available data suggest that transdermal testosterone formulations may offer a more favorable cardiovascular safety profile than intramuscular preparations, particularly with respect to erythrocytosis and pharmacokinetic stability, although head-to-head randomized trials with hard cardiovascular endpoints are still needed. Understanding the molecular mechanisms underlying these changes is essential for optimizing TRT in hypogonadal men with cardiovascular risk factors. The cardiovascular safety advantage of transdermal formulations is currently supported primarily by pharmacokinetic and hematological evidence; direct comparative evidence from randomized trials with hard cardiovascular endpoints remains unavailable. Full article

This study investigates titanium oxynitride (TiO_xN_y) coatings deposited by reactive magnetron sputtering on 316L stainless steel substrates in an Ar–N₂–O₂ gas mixture at a fixed N:O ratio of 1.6. The coatings were deposited under three reactive magnetron sputtering regimes with Ar flow rates of 33, 28, and 26 sccm and corresponding substrate biases of −50, −100, and −150 V, respectively, while the N₂ and O₂ flow rates were kept constant at 10 and 6 sccm. The coatings exhibited a dense microstructure, with thicknesses ranging from 2.13 to 5.51 μm. X-ray diffraction analysis revealed the formation of a multiphase structure comprising TiN, TiO_xN_y, and TiO. The deposition regime had a significant influence on the functional properties of the coatings. The lowest friction coefficients (µ ≈ 0.26–0.28) and stable tribological behavior were characteristic of the Ar26 sample. The highest corrosion resistance was observed for the Ar28 sample, with a corrosion current density of i_corr = 2.82 × 10⁻⁷ A/cm² and a corrosion rate of v_corr = 0.00573 mm/year. All coatings exhibited hydrophilic surface behavior, with contact angles of 50–57°, which may be relevant for further evaluation in biomedical surface applications. Thus, the structure and functional properties of TiO_xN_y coatings can be regulated by selecting an appropriate deposition regime, including the Ar flow rate, relative reactive gas fraction, and substrate bias. However, additional biological tests, including cytotoxicity, hemocompatibility, endothelialization, and platelet adhesion studies, are required before conclusions about vascular implant applicability can be made. Full article

Uncontrolled hemorrhage remains a major challenge in trauma care and surgical interventions, where rapid hemostasis and wound sealing are essential for improving patient survival. Natural polymer-based hydrogels have emerged as promising hemostatic materials owing to their excellent biocompatibility, biodegradability, and biomimetic properties. However, their clinical translation remains limited by insufficient mechanical robustness, wet adhesion, and functional responsiveness. To address these challenges, considerable progress has been achieved through rational material design and structural engineering strategies. Representative natural polymers, particularly polysaccharides and proteins, exhibit distinct physicochemical and biological characteristics that determine their hemostatic mechanisms and design strategies. Based on these material platforms, molecular modification strategies, including charge regulation, hydrophobic modification, and bioactive functionalization, have been widely employed to modulate interfacial interactions, platelet adhesion, coagulation activation, and tissue adhesion. In parallel, advanced structural architectures, such as porous, particulate, fibrous, multicrosslinked/multinetwork, and nanocomposite systems, have significantly enhanced fluid absorption, mechanical resilience, stress dissipation, and hemorrhage sealing efficiency. Beyond conventional hemostasis, increasing efforts have focused on integrating multifunctional properties, including antibacterial activity, inflammatory regulation, oxidative stress modulation, tissue regeneration, dynamic monitoring, and stimuli-responsive behaviors. This review systematically summarizes recent advances in natural polymer-based hemostatic hydrogels from the perspectives of advanced material modification strategies, structural engineering approaches, and functional integration, with particular emphasis on the relationships among material characteristics, interfacial behavior, structural organization, and hemostatic performance. Finally, current challenges and future perspectives for clinical translation are discussed, aiming to provide valuable insights for the rational design and clinical implementation of next-generation hemostatic biomaterials. Full article

Long-term clinical translation of left ventricular assist devices (LVADs) is severely hampered by thromboembolism and device-related infection, both originating from inadequate biocompatibility of the device-blood interface. Current titanium surface modifications fail to simultaneously deliver durable antithrombotic and antibacterial performance, while conventional polydopamine-copper (PDA-Cu) coatings suffer from inherent limitations. Herein, we report a one-step rapid co-polymerization strategy based on mussel-inspired polyphenol chemistry to fabricate a copper-integrated polydopamine/tannic acid nanocoating on titanium (Ti/PDT(Cu)). By incorporating tannic acid rich in catechol/pyrogallol moieties, we achieve synergistic acceleration of dopamine oxidative polymerization with copper ions, dramatically shortening the fabrication time to 8 h (vs. 24 h for traditional PDA coatings). This process simultaneously constructs a robust dual-crosslinked network through covalent/hydrogen bonds and metal-phenolic coordination, exhibiting a uniform nanoscale-roughened structure. Comprehensive physicochemical characterizations confirm homogeneous coating deposition, excellent hydrophilicity, uniform Cu distribution, and superior long-term structural stability (95.68% thickness retention after 7 days of physiological immersion). The optimized coating displays broad-spectrum and durable antibacterial activity, with 92.79% and 89.73% reduction of E. coli and S. aureus at 24 h, respectively, and retains $>$89% antibacterial efficacy after 7 days of continuous elution (n = 3, * p$<$ 0.05). Moreover, the coating enables stable and sustained catalytic nitric oxide generation (43.85 $\pm$ 2.36 μM cumulative release over 14 days) that mimics endothelial function, resulting in 69.4% inhibition of platelet adhesion and an ultralow hemolysis ratio of 0.97% (n = 3). Critically, it maintains excellent cytocompatibility with L929 fibroblasts ($>$90% cell viability after 72 h co-culture). This work addresses key limitations of conventional PDA-based functional coatings, realizes synergistic antithrombotic and antibacterial dual functions showing great potential for blood-contacting cardiovascular device applications, and provides a facile and robust surface engineering platform for long-term implantable cardiovascular devices. Full article

Background/Objectives: This investigation was performed because corticosteroid injections are commonly used for symptomatic relief in patients with meniscal deficiency, yet their effect on graft survivorship and postoperative outcomes following meniscal allograft transplantation (MAT) remains poorly understood, with limited literature specifically addressing this topic. The aim of this study is to evaluate whether preoperative intra-articular corticosteroid injections (ICS) are associated with reoperation after MAT. Secondary aims included comparing reoperation-free survival, patient-reported outcome measures (PROMs), and patient acceptable symptom state (PASS) achievement. Methods: A retrospective review of 130 adults undergoing meniscal allograft transplantation (MAT) between 2011 and 2023 was performed. Patients with documented corticosteroid injection (CSI) status and ≥2 years of follow-up were included. Exclusion criteria included prior meniscal allograft transplantation, receipt of non-corticosteroid injections (e.g., hyaluronic acid or platelet-rich plasma), concomitant osteotomy procedures, multi-ligament knee reconstruction or inadequate follow-up. Propensity score matching (2:1 no steroid: steroid) based on age, sex, body mass index, fixation technique, operative compartment, and concomitant procedures yielded 54 matched patients (35 no steroid, 19 steroid). The primary outcome was ipsilateral knee reoperation, categorized as major reoperation (revision MAT, anterior cruciate ligament reconstruction, osteochondral allograft transplantation, conversion to total knee arthroplasty, meniscectomy and meniscus repair). Minor reoperations included irrigation and debridement, lysis of adhesions or manipulation under anesthesia, hardware removal, chondroplasty, and synovectomy. Reoperation-free survival was assessed using Kaplan–Meier analysis. PROMs and PASS were compared using adjusted regression models. Statistical significance was set at p < 0.05. Results: Baseline characteristics and follow-up were comparable between groups (7.6 ± 3.5 vs. 6.6 ± 3.2 years; p = 0.30). Overall reoperation occurred in 37.1% of patients in the no-steroid group and 31.6% in the steroid group (p = 0.771). Major reoperation rates were similar (17.1% vs. 15.8%; p = 1.000. There was no significant difference in minor reoperations between groups (20.0% vs. 10.5%; p = 0.468). Kaplan–Meier analysis demonstrated no difference in reoperation-free survival (p = 0.903), with comparable survival at the 1-, 2-, and 5-year time points. No individual subtypes differed significantly between groups. PROMs and PASS achievement were also similar, with no statistically significant differences observed. Conclusions: Preoperative corticosteroid injection was not associated with increased reoperation risk, inferior reoperation-free survival, or worse patient-reported outcomes following meniscal allograft transplantation. However, given the study’s limited power, lack of detailed injection characteristics, and the use of a heterogeneous complication outcome, these findings should be interpreted cautiously, as further investigation is warranted. Full article

Background: The generation of durable and hemocompatible small-diameter vascular grafts remains a major challenge in current vascular tissue engineering, as clinically available synthetic grafts are lacking hemocompatibility resulting in limited long-term patency. In recent years, fibrin has emerged as a promising scaffold material for various tissue engineering approaches due to its autologous nature, controllable fabrication, and mechanical properties. However, although pivotal for the translation into clinical application, systematic evaluation of hemocompatibility in fibrin-based small-caliber grafts is still missing. Methods: Here, the hemocompatibility of small-diameter fibrin-based grafts with and without heparin coating was compared to the current gold standard for prosthetic small-diameter vessel replacement in the form of heparin-coated ePTFE grafts using the Chandler Loop circulation model with human whole blood. Cell adhesion of thrombocytes, erythrocytes, and leucocytes was compared. Platelet activation, activation of the complement system, and plasmatic coagulation activity were assessed by ELISA analyses for P-Selectin, complement sC5b-9, and thrombin–antithrombin complex, respectively. Scanning electron microscopy (SEM) was performed to evaluate interactions and thrombocyte activation on the luminal graft surfaces. Results: The short-term hemocompatibility of the fibrin-based grafts with respect to the cell-count, activation of the coagulation pathways, and thrombocyte activation was comparable to the heparin-coated synthetic grafts even without heparin coating of the bioartificial grafts. Conclusions: The findings of this early-stage analysis support fibrin as a promising scaffold material for small-diameter vascular tissue engineering. Full article

Despite the widespread use of polyurethane (PU) in biomedical devices, its long-term application has been hindered by insufficient hemocompatibility caused by protein adsorption and subsequent thrombosis. In this study, a fluorinated PU (F–PCU) was designed to improve surface hemocompatibility while maintaining mechanical performance and good cytocompatibility. F–PCU was synthesized via a prepolymer method using a fluorinated diol and an ordered hard-segment extender. The chemical structure, thermal behavior, and mechanical properties were systematically characterized, while surface properties and biological performance were evaluated by water contact angle, protein adsorption, platelet adhesion, and cytotoxicity assays. The results demonstrated that fluorinated side chains preferentially enriched at the surface, forming a low-energy interface with significantly enhanced hydrophobicity. F–PCU exhibited excellent mechanical properties with a tensile strength of 49.5 MPa and an elongation at break of 965%. Notably, protein adsorption and platelet adhesion were substantially reduced, while good cytocompatibility was maintained, indicating improved surface hemocompatibility. These findings suggest that integrating ordered hard segments with fluorinated side chains is an effective strategy to optimize both bulk and surface properties, offering promising potential for long-term biomedical applications. Full article

Mesenchymal stromal cell (MSC) adhesion and retention at sites of cartilage degeneration are critical for improving cartilage repair. This study investigated whether platelet-rich plasma (PRP) enhances the adhesion and short-term retention of bone marrow-derived MSCs (BM-MSCs) and chondrocytes under in vitro and ex vivo conditions. BM-MSCs and chondrocytes were treated with PRP or pretreated with PRP for 10 or 30 min, and cell adhesion to collagen-coated surfaces was evaluated using a cell viability assay. Ex vivo adhesion and short-term retention of BM-MSCs on osteochondral discs with varying lesion severity were assessed by fluorescence imaging analysis. PRP significantly enhanced the adhesion of both BM-MSCs and chondrocytes in a time-dependent manner, with the 30 min PRP pretreatment group showing the greatest effect. BM-MSC attachment in the 30 min PRP pretreatment group was significantly higher than that in the untreated control group after 30 min of incubation (p < 0.001), whereas chondrocyte attachment was also significantly increased following PRP pretreatment. In addition, PRP pretreatment significantly enhanced BM-MSC attachment compared with PRP treatment alone at 20 and 30 min of incubation (both p < 0.001). In ex vivo experiments, adhesion and short-term retention increased significantly with increasing lesion severity from G1 to G3 (p < 0.05 and p < 0.01, respectively). In G2 and G3 lesions, PRP pretreatment for 30 min significantly enhanced BM-MSC adhesion and short-term retention compared with the control group (both p < 0.01). These findings suggest that PRP may improve the early adhesion and retention of MSCs on damaged cartilage and support the potential use of PRP as a biological adjunct for MSC-based cartilage repair strategies. Full article

Sepsis is a systemic disorder in which infection-induced inflammation progressively disrupts vascular homeostasis and drives organ dysfunction. This review reframes septic pathophysiology as a sequential and self-amplifying process centered on endothelial failure. Early activation of innate immune pathways by pathogen- and damage-associated molecular patterns promotes cytokine release, oxidative stress, and enzymatic degradation of the endothelial glycocalyx. Loss of this protective surface layer exposes endothelial cells to unbuffered inflammatory and mechanical injury, impairing mechanotransduction, increasing leukocyte and platelet adhesion, and destabilizing vascular barrier function. Subsequent disruption of intercellular junctions promotes capillary leakage, tissue edema, and impaired oxygen diffusion, while mitochondrial dysfunction and redox imbalance reduce endothelial repair capacity. In parallel, complement activation, neutrophil extracellular trap formation, platelet–leukocyte interactions, and loss of anticoagulant signaling shift the microvasculature toward a prothrombotic and proinflammatory state. These interconnected mechanisms culminate in microvascular incoherence, characterized by heterogeneous capillary flow, regional hypoxia, impaired oxygen extraction, and progressive organ failure despite apparent restoration of systemic hemodynamics. Within this framework, biomarkers such as syndecan-1, soluble thrombomodulin, angiopoietin-2, von Willebrand factor, and plasminogen activator inhibitor-1 are best interpreted as mechanistic readouts of glycocalyx shedding, endothelial injury, permeability imbalance, and thromboinflammatory activation. Understanding sepsis as an evolving endothelial pathophysiological process provides a coherent framework for integrating inflammation, vascular leakage, hypoxia, coagulation, and organ dysfunction while identifying mechanistic biomarkers that reflect distinct stages of microvascular collapse. Full article

Below 32 °C, the second irreversible stage of platelet aggregation is absent, causing augmentation of the first reversible stage of platelet aggregation and adhesion. During rewarming, de-aggregation occurs; however, in the presence of adequate ADP (adenosine diphosphate), the second stage of aggregation occurs, leading to delayed rewarming thrombocytopenia (DRT). Erythrocytes leak ADP in sufficient amounts by 24 h to cause DRT. This is prevented by rewarming within 24 h. Heparin before hypothermia prevents platelet adhesion, as does alcohol, which also blocks the second phase of aggregation. Aspirin blocks the second phase of aggregation, and platelet infusions, stored without erythrocytes, are an effective therapy. DRT explains rewarming deaths in NCI (neonatal cold injury). Full article

Thrombosis remains a critical challenge for blood-contacting implants, with early-stage protein adsorption and platelet activation playing decisive roles. In this study, we constructed a TiO₂/CuO semiconductor heterojunction on titanium surfaces to generate a stable built-in electric field, creating a self-activated bioelectric microenvironment without external stimulation. We evaluated its cytocompatibility and hemocompatibility through static in vitro assays. To distinguish the contributions of surface chemistry, topography, and bioelectric cues, we include control groups of Ti (untreated), TNW (TiO₂ network, topography control), and Ti/CuO (CuO nanoparticles without heterojunction, Cu²⁺ release control). The heterojunction significantly enhances human umbilical vein endothelial cell (HUVEC) adhesion and proliferation while simultaneously suppressing fibrinogen adsorption, platelet adhesion/activation (as assessed by morphological changes), and whole-blood cell adhesion. Compared with Ti/CuO, the heterojunction (TCH) induces substantially stronger endothelialization and anticoagulant effects despite similar Cu²⁺ release levels (~0.047 μM, far below the reported pro-angiogenic threshold of ~5.0 μM), indicating a predominant role of the built-in electric field. This study preliminarily demonstrates a previously unrecognized role of bioelectric cues in modulating early blood–material interactions. Following rigorous validation under physiologically relevant dynamic flow conditions and in vivo models, interfacial bioelectric engineering emerges as a promising new strategy for designing anticoagulant biomaterials. Full article

Gelatin methacrylate (GelMA) hydrogels are promising carriers for bioactive agents like curcumin (Cur) and adenosine diphosphate (ADP) in wound healing. However, existing GelMA-based systems fail to achieve both rapid hemostasis and sustained anti-inflammatory effects. In this study, we developed a Cur/ADP GelMA hydrogel, and evaluated its anti-inflammatory, regenerative, hemostatic, and biocompatible properties. Proton nuclear magnetic resonance (¹H-NMR) analysis showed that a 65% degree of substitution of GelMA is optimal for wound dressings. Scanning electron microscopy revealed a uniform pore size, aiding inflammatory exudate removal. The Cur/ADP GelMA hydrogel exhibited strong adhesion, stability, and antibacterial activity, reducing E. coli and S. aureus proliferation by 85% and 72%, respectively. Hemostatic effects were observed, with blood loss reduced to 238 ± 23 mg compared to 559 ± 18 mg in the untreated group. The ELISA results showed reduced pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and increased IL-10. In vivo studies demonstrated 98% wound closure by day 14, enhanced granulation tissue formation, and a 70% thicker epidermis compared to controls. Mechanistically, ADP accelerates platelet activation and clot formation, while Cur modulates the inflammatory microenvironment, enabling synergistic hemostasis and immune regulation, thus promoting accelerated wound healing. Full article

Objectives: Seawater-immersed burn wounds are highly susceptible to contamination, persistent inflammation, oxidative stress, and delayed healing, while current irrigation solutions remain suboptimal for such acute injuries. This study aimed to evaluate the therapeutic efficacy and underlying mechanisms of plasma-activated water (PAW) as a novel irrigation strategy for these complex wounds. Methods: The antibacterial efficacy of PAW against marine pathogens was first evaluated in vitro. Subsequently, a rat model of seawater-immersed burn injury was established in male Sprague-Dawley (SD) rats to assess the therapeutic effects of PAW irrigation on wound healing, infection control, and underlying biological mechanisms. Results: In vitro, PAW significantly eradicated two major marine pathogens, Vibrio vulnificus and Vibrio parahaemolyticus (p < 0.001). In vivo, PAW markedly accelerated wound closure, achieving complete healing in 23.60 ± 6.50 days vs. 38.67 ± 2.08 days (Normal saline group) and 58.33 ± 10.97 days (Model group) (p < 0.05). PAW significantly reduced bacterial burden, modulated inflammation by decreasing interleukin-6 and increasing interleukin-10, and alleviated oxidative stress, as evidenced by reduced malondialdehyde levels and enhanced superoxide dismutase activity. Histological evaluation demonstrated enhanced re-epithelialization, collagen deposition, and increased expression of vascular endothelial growth factor and platelet endothelial cell adhesion molecule-1. No adverse effects on serum biochemistry or major organ histopathology were observed. Conclusions: PAW may be a safe, promising, and multifunctional irrigation strategy that promotes seawater-immersed burn healing through coordinated antibacterial, anti-inflammatory, antioxidant, and pro-angiogenic effects, highlighting its strong potential for clinical translation. Full article