Tissue-specific gene expression defines cellular identity and function, but knowledge of early human development is limited, hampering application of cell-based therapies. Here we profiled 5 distinct cell types at a single fetal stage, as well as chondrocytes at 4 stages in vivo and 2 stages during in vitro differentiation. Network analysis delineated five tissue-specific gene modules; these modules and chromatin state analysis defined broad similarities in gene expression during cartilage specification and maturation in vitro and in vivo, including early expression and progressive silencing of muscle- and bone-specific genes. Finally, ontogenetic analysis of freshly isolated and pluripotent stem cell-derived articular chondrocytes identified that integrin alpha 4 defines 2 subsets of functionally and molecularly distinct chondrocytes characterized by their gene expression, osteochondral potential in vitro and proliferative signature in vivo. These analyses provide new insight into human musculoskeletal development and provide an essential comparative resource for disease modeling and regenerative medicine.

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Current study demonstrates a direct role for CaMKII in TGF-β and BMP-mediated responses in primary and PSC-derived chondrocytes. These findings have direct implications for tissue engineering of cartilage tissue from stem cells and therapeutic management of OA.

Background: Tibial eminence fractures are bony avulsions of the anterior cruciate ligament from its insertion on the intercondylar eminence. Numerous anatomic factors have been associated with anterior cruciate ligament injuries, such as posterior tibial slope, but there are few studies evaluating the association with tibial eminence fracture. Purpose: To compare posterior tibial slope of pediatric patients with and without tibial eminence fractures. We hypothesized that a steeper posterior tibial slope would be associated with tibial eminence fracture. Study Design: Cohort study; Level of evidence, 3. Methods: Patients who underwent surgical treatment of tibial eminence fracture were retrospectively identified between January 2000 and July 2021. Adults aged >20 years and those without adequate imaging were excluded. Controls without gross ligamentous or osseous pathology were identified. Descriptive information and Meyers and McKeever classification were recorded. Posterior tibial slope measurements were obtained by 2 independent orthopaedic surgeons twice, with measurements separated by 3 weeks. Chi-square tests and independent-samples t tests were used to compare posterior tibial slope and patient characteristics. Inter- and intrareviewer variability was determined via the intraclass correlation coefficient. Results: A total of 51 patients with tibial eminence fractures and 57 controls were included. By sex, tibial eminence fractures occurred among 34 male and 17 female patients with a mean age of 10.9 years. The posterior tibial slope among those with tibial eminence fractures (9.7°) was not significantly greater than that of controls (8.8°; P = .07). Male patients with a tibial eminence fracture had significantly steeper slopes compared with controls (10.0° vs 8.4°; P = .006); this difference was not observed between female patients and female controls. Patients with a slope ≥1 SD above the mean (12.0°) had 3.8 times greater odds (95% CI, 1.3-11.6; P = .017) of having a tibial eminence fracture. Male patients with a posterior tibial slope >12° had 5.8 times greater odds (95% CI, 1.1-29.1; P = .034) of having a tibial eminence fracture compared with male controls. Conclusion: Male patients undergoing surgical fixation of a tibial eminence fracture had an increased posterior tibial slope as compared with case-controls. Increased posterior tibial slope may be a risk factor for sustaining a tibial eminence fracture, although the clinical significance of this deserves further investigation.

Background Bone fractures are one of the most common injuries in the USA. Fiberglass tape is a commonly used casting material, and many medical professionals apply adjuvants including liquid hand soap, foam sanitizers, and ultrasound gel in the hopes of improving outcomes relating to ease of molding and eventual strength, lamination, and smoothness of cast material. However, the efficacy of these agents to improve fiberglass cast mechanics has not been scientifically evaluated. The purpose of this study was to assess the mechanical effects of commonly used adjuvants on fiberglass cast materials. Methods Studies compared regularly shaped samples of water-activated, untreated fiberglass tape (Ossur Techform Premium) to water-activated fiberglass tape treated with one of three commonly used adjuvants (liquid soap, foam hand sanitizer, or ultrasound gel) during lamination. Material stiffness, yield stress, and ultimate load were measured by 3-point bending. Results These studies demonstrated that that liquid soap and ultrasound gel did not affect fiberglass tape mechanical properties, but alcohol-based foam sanitizer significantly reduced stiffness (− 32.8%), yield stress (− 33.6%), and ultimate load (− 31.0%) of the cast material as compared to the control group. Regression slopes were not significantly different between groups, suggesting that no adjuvants improved material curing time. Conclusions These data suggest that the application of adjuvants is not beneficial and potentially harmful to fiberglass cast behavior. Despite the widespread practice of adjuvant application by medical professionals during casting, results from the current study suggest that use of these agents for structural enhancement of fiberglass casts is not beneficial and should largely be discouraged. Electronic supplementary material The online version of this article (10.1186/s13018-019-1202-1) contains supplementary material, which is available to authorized users.

Umbilical cord blood (UCB) has been increasingly explored as an alternative source of stem cells for use in regenerative medicine due to several advantages over other stem-cell sources, including the need for less stringent human leukocyte antigen matching. Combined with an osteoinductive signal, UCB-derived mesenchymal stem cells (MSCs) could revolutionize the treatment of challenging bone defects. This study aimed to develop an ex vivo regional gene-therapy strategy using BMP-2-transduced allogeneic UCB-MSCs to promote bone repair. To this end, human UCB-MSCs were transduced with a lentiviral vector carrying the cDNA for BMP-2 (LV-BMP-2). In vitro assays to determine the UCB-MSC osteogenic potential and BMP-2 production were followed by in vivo implantation of LV-BMP-2-transduced UCB-MSCs in a mouse hind-limb muscle pouch. Non-transduced and LV-GFP-transduced UCB-MSCs were used as controls. Transduction with LV-BMP-2 was associated with abundant BMP-2 production and induction of osteogenic differentiation in vitro. Implantation of BMP-2-transduced UCB-MSCs led to robust heterotopic bone formation 4 weeks postoperatively, as seen on radiographs and histology. These results, along with the fact that UCB-MSCs can be easily collected with no donor-site morbidity and low immunogenicity, suggest that UCB might be a preferable allogeneic source of MSCs to develop an ex vivo genetherapy approach to treat difficult bone-repair scenarios.

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Private insurance is designed to provide more timely and cost-effective medical care. With the increase in healthcare deductibles, however, patients are delaying operative management of a variety of pathologies toward the end of the fiscal year with the hopes of having met their deductible. In this retrospective review, the authors assess the operative timing of common orthopedic upper extremity surgeries between publicly and privately insured patients at both university and physician-owned medical institutions.