Hss Journal最新文献

The possibility of modifying disease through regenerative medicine applications, particularly stem cell therapies, raises ethical and regulatory challenges in orthopedics. This review article provides historical context of stem cell research, ethical issues such as informed consent, therapeutic misconception, and equitable access, emphasizing the responsibilities of providers offering investigational treatments. It also examines the evolving role of the U.S. Food and Drug Administration (FDA) in regulating regenerative therapies through frameworks like the Regenerative Medicine Advanced Therapy (RMAT) designation, and more point-of-care enforcement discretion policies for therapies such as autologous micro-fragmented adipose tissue and bone marrow aspirate concentrate. The authors underscore the importance of innovative therapies to address unmet needs in musculoskeletal healthcare while acknowledging the need for more rigorous basic and clinical research. They call for a continuous refinement of regulatory and ethical standards as regenerative medicine advances.

Adipose-derived cellular therapies, including stromal vascular fraction (SVF) and adipose-derived stem cells (ASCs), have demonstrated increasing therapeutic potential across regenerative medicine applications. This narrative review examines the current evidence supporting the use of SVF and ASCs in 2 primary clinical contexts: osteoarthritis (OA) and chronic wound healing. SVF, a heterogeneous cell population isolated from lipoaspirated fat via enzymatic or mechanical methods, and ASCs, a more homogeneous culture-expanded mesenchymal cell product, both exert regenerative effects through angiogenic, immunomodulatory, and reparative mechanisms. In OA, both cell types have been shown to significantly reduce pain and improve function, with some studies indicating cartilage regeneration on imaging. While ASCs may offer faster symptom relief due to higher purity and dosing, SVF remains a more accessible, minimally manipulated alternative with comparable long-term outcomes. In wound healing, adipose-derived therapies have been associated with accelerated closure of chronic ulcers through enhanced neovascularization, modulation of the inflammatory microenvironment, and promotion of granulation tissue and re-epithelialization. Across both indications, these therapies have shown a good safety profile, with minimal adverse events reported. The review also addresses regulatory distinctions, standardization challenges, and biologic variability, particularly in SVF preparations. Taken together, the evidence suggests the clinical utility of adipose-derived cellular therapies while highlighting the need for further standardization, long-term safety monitoring, and large-scale randomized trials to confirm efficacy and optimize clinical translation.

Nano-sized extracellular vesicles enclosed by a lipid bilayer and secreted by various cell types including mesenchymal stem cells, exosomes act as natural transporters, carrying bioactive molecules such as proteins, lipids, and nucleic acids that mediate intercellular communication. Exosomes influence a range of cellular processes, including immune modulation, tissue repair, and disease progression. Compared to whole-cell therapies, exosomes provide anti-inflammatory, immunosuppressive, and regenerative effects with reduced risks linked to cellular components, such as infusion toxicity, immunogenicity, and tumorigenic phenomena. This article reviews isolation, modification, characterization, and storage techniques, challenges in clinical translation, and innovative engineering strategies to enhance targeting and efficacy. It also examines preliminary evidence suggesting that exosomes may have potential in managing degenerative disorders such as osteoarthritis, intervertebral disc degeneration, osteoporosis, osteonecrosis, and tendinopathy, as well as non-degenerative disorders such as sciatic nerve injury, fractures, and soft tissue trauma.

Background: The formation of a stable fibrin clot plays an important role in early tissue repair. Tranexamic acid (TXA), a potent fibrinolysis inhibitor, prevents fibrin clot dissolution.

Purpose: We sought to test the effect of intra-articular TXA administration on meniscus healing and articular cartilage status in a rabbit model.

Methods: Thirty-two rabbits underwent bilateral knee surgery with creation of a 1.5-mm circular defect in the anterior horn of the lateral meniscus and a 3-mm longitudinal tear with repair in the anterior horn of the medial meniscus. Twelve rabbits were used for an initial TXA dose determination study. Twenty rabbits were then injected with 50 mg/mL of TXA in the left knee while the right knee served as a control. Animals were sacrificed at 2-, 4-, and 8-week timepoints. Eight rabbits underwent biomechanical analysis. Semiquantitative histological analysis compared meniscal healing and articular cartilage between TXA-treated and control knees.

Results: Both circular defects of the lateral meniscus and longitudinal tear injuries of the medial meniscus showed no difference in healing across all timepoints. At 2 weeks post-surgery, TXA-treated knees exhibited reduced tibial articular cartilage structure compared to controls. By week 8, control knees had higher proteoglycan content in all femoral articular cartilage zones compared to TXA-treated knees. Biomechanical analysis was inconclusive.

Conclusion: This rabbit study found that TXA administration did not enhance healing following meniscus repair. Moreover, intra-articular TXA appeared to have exerted an adverse effect on articular cartilage, possibly due to the detrimental effects of persistent blood in a joint. Further studies will be critically important to determine the effect of TXA administration at various time points after surgical repair.

Background: Regenerative therapies are being studied for use in several orthopedic conditions, but as these approaches gain in popularity, insurance coverage denials have become a critical issue for patients, physicians, hospitals, and payers.

Purpose: We sought to analyze the references commercial payers use to support their policies denying coverage for orthopedic applications of mesenchymal stem cell (MSC) therapy.

Methods: We reviewed the policies regarding orthopedic applications of MSC therapy of the top 11 national commercial health insurance payers, 5 of which had publicly accessible policies. Supporting references were screened by title and/or abstract. Selected references were categorized by type of reference and reviewed for level of evidence (LOE), anatomic location under investigation, and type and source of MSC. Studies that were not LOE I or II were defined as low LOE. Finally, efficacy of the therapy was recorded in a binary fashion.

Results: To support denial of coverage for MSC use in orthopedics, the 5 insurance companies cited a majority of level IV evidence, despite available and pertinent level I and II studies on the subject. The knee was the most common anatomic location investigated and, along with the spine, the most likely to report favorable outcomes with MSC use. Primary journal articles and studies with higher LOE were more likely to report favorable outcomes than review articles or those with lower LOE.

Conclusion: This analysis of 5 commercial insurance payers' policies found that they substantiate their denial of coverage for MSC use in orthopedic applications primarily with low-level evidence. It also found that higher-level evidence, when cited, often points to the potential efficacy of MSCs.

Background: Body protection compound-157 (BPC-157) is a naturally occurring gastric peptide that promotes mucosal integrity and homeostasis. Preclinical studies show its potential for promoting healing in musculoskeletal injuries such as fractures, tendon ruptures, ligament tears, and muscle injuries. Despite lacking US Food and Drug Administration approval and its use being banned in professional sports, it is increasingly used by clinicians and athletes. Purpose: We sought to (1) provide a comprehensive synthesis of the BPC-157 literature from an orthopedic sports medicine perspective and (2) elucidate the mechanism of action, musculoskeletal effects, metabolism, and safety profile. Methods. We conducted a systematic review of English-language literature, published from database inception to June 3, 2024, from PubMed, Cochrane, and Embase. We searched PROSPERO to identify any current or unpublished reviews. Studies reporting BPC-157's mechanism, musculoskeletal outcomes, metabolism, and safety were included. Articles were screened in 3 phases by 2 reviewers. In cases of a disagreement between the 2 reviewers, blinding was removed, and eligibility was determined by group consensus, with a third author making the final decision. Results. A total of 544 articles from 1993 to 2024 were identified. After duplicates were removed, 36 studies were included (35 preclinical studies, 1 clinical study). The studies suggest that BPC-157 enhances growth hormone receptor expression and several pathways involved in cell growth and angiogenesis, while reducing inflammatory cytokines. In preclinical models, BPC-157 improved functional, structural, and biomechanical outcomes in muscle, tendon, ligament, and bony injuries. In a retrospective study of musculoskeletal pain following intraarticular injection of BPC-157 for unspecified chronic knee pain, 7 of 12 patients reported relief for >6 months. BPC-157 is metabolized in the liver, with a half-life of less than 30 minutes, and is cleared by the kidneys. Preclinical safety studies showed no adverse effects across several organ systems. No clinical safety data were found. Conclusion: This systematic review of level IV and level V studies suggests that BPC-157 shows promise for promoting recovery from musculoskeletal injuries. Adverse effects are possible due to unregulated manufacturing, contamination, or unknown clinical safety. We recommend that clinicians counsel athletes to understand their organizations' rules to remain compliant with medication/supplement safety and testing standards.

Background: Long-term use of corticosteroids is a known risk factor for various bone diseases. Corticosteroids disrupt the balance between oxidative and glycolytic energy metabolism, increase oxidative stress and reactive oxygen species (ROS) associated with prolongation of inflammation, cell apoptosis, deficits in mesenchymal stem cells (MSCs), and osteoclast differentiation. Metformin, a drug for diabetes, has antioxidant properties by inhibiting nicotinamide adenine dinucleotide phosphate oxidase, which promotes the production of ROS.

Purpose: We sought to evaluate the effects of corticosteroid and metformin administration on MSCs in vitro.

Methods: Primary bone marrow MSCs were collected from 20 mice. We evaluated prednisolone's effects on cell proliferation, oxidative stress, osteogenic differentiation, and mineralization, followed by metformin's effect on corticosteroid-induced reduction in bone formation. Metformin (1, 10, 100 µM) was tested with prednisolone 3 ng/mL. Cytokines were assessed by Luminex.

Results: Prednisolone at 3 ng/mL significantly reduced cell proliferation, while 10 µM metformin restored it. Prednisolone increased oxidative stress and was reversed by metformin in a concentration-dependent manner, particularly at 100 µM. Osteogenic differentiation and mineralization were significantly impaired with prednisolone but improved with metformin at 10 and 100 µM. As for inflammatory cytokines, interleukin-1β (IL-1β) expression was increased by prednisolone administration and suppressed by metformin. Conversely, IL-6 and monocyte chemotactic protein-1 were suppressed by prednisolone.

Conclusion: This in vitro study found that corticosteroid-associated decrease in osteogenic potential of murine MSCs was associated with elevated oxidative stress that can be alleviated by metformin; further studies are needed to validate these findings in vivo and with human-derived MSCs.

Background: Minimally invasive surgery (MIS) has shown the potential in reducing surgical site infection (SSI); however, its impact on instrumented lumbar fusion procedures remains unclear. Purpose: We sought to investigate the difference in SSI rates for open, mini-open, and MIS techniques in patients who underwent posterior lumbar instrumented fusions. Methods: We conducted a retrospective review of all patients at a single academic institution who underwent instrumented 1- or 2-level posterior lumbar fusion between January 2019 and June 2022. Cases were allocated to 1 of 3 mutually exclusive surgical cohorts (MIS, mini, or open). SSIs were diagnosed based on the National Healthcare Safety Network criteria. Results: A total of 1352 patients were reviewed for a total of 1382 lumbar fusion operations included in this study. The mean age was 61.5 ± 12.8 years, and the mean body mass index was 28.7 ± 5.67 kg/m². The largest cohort was open (39.3%, 543), followed by mini (33.1%, 458) and MIS (27.6%, 381). Thirteen patients (0.94%) developed an SSI. There were no statistically significant differences in the infection rates between the cohorts; SSI rates were MIS (0.3%, 1), mini (1.1%, 5), and open (1.3%, 7). Twelve (92%) of the patients with an SSI underwent a subsequent irrigation and debridement procedure; on average, this occurred 42.2 ± 25 days postoperatively. Conclusions: This retrospective review found that 0.94% of patients developed an SSI following a 1- or 2-level posterior lumbar instrumented fusion. Although the observed SSI rate in the open cohort was 4 times higher than in the MIS cohort, the sample sizes were insufficient to determine statistically significant differences between the 3 surgical approaches. Nonetheless, our data suggests that all 3 techniques evaluated had exceptionally low infection rates.