Engineered phalangeal grafts for children with symbrachydactyly: A proof of concept.

Tissue engineering approaches hold great promise in the field of regenerative medicine, especially in the context of pediatric applications, where ideal grafts need to restore the function of the targeted tissue and consider growth. In the present study, we aimed to develop a protocol to engineer autologous phalangeal grafts of relevant size for children suffering from symbrachydactyly. This condition results in hands with short fingers and missing bones. A previously-described, developmentally-inspired strategy based on endochondral ossification (ECO)-the main pathway leading to bone and bone marrow development-and adipose derived-stromal cells (ASCs) as the source of chondroprogenitor was used. First, we demonstrated that pediatric ASCs associated with collagen sponges can generate hypertrophic cartilage tissues (HCTs) in vitro that remodel into bone tissue in vivo via ECO. Second, we developed and optimized an in vitro protocol to generate HCTs in the shape of small phalangeal bones (108-390 mm3) using freshly isolated adult cells from the stromal vascular fraction (SVF) of adipose tissue, associated with two commercially available large collagen scaffolds (Zimmer Plug® and Optimaix 3D®). We showed that after 12 weeks of in vivo implantation in an immunocompromised mouse model such upscaled grafts remodeled into bone organs (including bone marrow tissues) retaining the defined shape and size. Finally, we replicated similar outcome (albeit with a slight reduction in cartilage and bone formation) by using minimally expanded pediatric ASCs (3 × 106 cells per grafts) in the same in vitro and in vivo settings, thereby validating the compatibility of our pediatric phalanx engineering strategy with a clinically relevant scenario. Taken together, these results represent a proof of concept of an autologous approach to generate osteogenic phalangeal grafts of pertinent clinical size, using ASCs in children born with symbrachydactyly, despite a limited amount of tissue available from pediatric patients.

Harnessing human adipose-derived stromal cell chondrogenesis in vitro for enhanced endochondral ossification.

Endochondral ossification (ECO), the major ossification process during embryogenesis and bone repair, involves the formation of a cartilaginous template remodelled into a functional bone organ. Adipose-derived stromal cells (ASC), non-skeletal multipotent progenitors from the stromal vascular fraction (SVF) of human adipose tissue, were shown to recapitulate ECO and generate bone organs in vivo when primed into a hypertrophic cartilage tissue (HCT) in vitro. However, the reproducibility of ECO was limited and the major triggers remain unknown. We studied the effect of the expansion of cells and maturation of HCT on the induction of the ECO process. SVF cells or expanded ASC were seeded onto collagen sponges, cultured in chondrogenic medium for 3-6 weeks and implanted ectopically in nude mice to evaluate their bone-forming capacities. SVF cells from all tested donors formed mature HCT in 3 weeks whereas ASC needed 4-5 weeks. A longer induction increased the degree of maturation of the HCT, with a gradually denser cartilaginous matrix and increased mineralization. This degree of maturation was highly predictive of their bone-forming capacity in vivo, with ECO achieved only for an intermediate maturation degree. In parallel, expanding ASC also resulted in an enrichment of the stromal fraction characterized by a rapid change of their proteomic profile from a quiescent to a proliferative state. Inducing quiescence rescued their chondrogenic potential. Our findings emphasize the role of monolayer expansion and chondrogenic maturation degree of ASC on ECO and provides a simple, yet reproducible and effective approach for bone formation to be tested in specific clinical models.

The association between objective sleep duration and diet. The CoLaus|HypnoLaus study.

BACKGROUND AND AIMS: Sleep deprivation is frequently associated with an unhealthy diet. So far, most studies used reported sleep duration. We assessed the associations between objectively measured sleep duration and dietary intake. METHODS: Cross-sectional study conducted between 2009 and 2013 on 1910 participants (49.5% women, 58.3 ± 11.0 years) living in Lausanne, Switzerland. Total sleep time (TST) was assessed using polysomnography and categorized into <7, 7-9 and >9 hours/day. Total energy, macro and micronutrients intake, dietary adequacy scores and compliance to Swiss dietary recommendations were assessed. RESULTS: There were 60.6%, 37.2% and 2.2% of the participants in the categories <7, 7-9 and >9 h/day, respectively. Body mass index was higher in the >9 h/d sleep category. After multivariate adjustment, significant (p < 0.05) differences were found between sleep categories regarding total carbohydrates (46.6 ± 8.6, 46.0 ± 8.8 and 48.1 ± 8.0% of total energy intake for <7, 7-9 and >9 h/day, respectively), mono and disaccharides (22.7 ± 8.0, 22.4 ± 8.3 and 25.2 ± 8.8), and total fat (33.9 ± 6.4, 34.7 ± 6.9 and 34.2 ± 5.8). No association was found for total energy intake, other nutrients, dietary adequacy scores, dietary patterns or compliance to dietary guidelines. The differences in mono and disaccharides were found in women and the differences in total fat in men, although sex-diet intake interactions were not significant. Sensitivity analyses excluding participants with sleep apnea, using quartiles of TST or subjective sleep duration yielded similar conclusions. CONCLUSION: Little if no associations were found between objectively measured TST and dietary intake in a Swiss general adult population. The associations with total carbohydrate, mono and disaccharide and total fat intake deserve further investigation.

3D-Printed Hand Splints versus Thermoplastic Splints: A Randomized Controlled Pilot Feasibility Trial.

In this randomized controlled pilot trial, we compared three-dimensional (3D)-printed made-to-measure splints to conventional custom-made thermoplastic splints. In a clinical setting, we evaluated their general applicability and possible benefits for immobilization in hand surgical patients. We included 20 patients with an indication for immobilization of at least 4 weeks, regardless of the splint design. Patient comfort and satisfaction were assessed with questionnaires at splint fitting, as well as 2 and 4-6 weeks later. The 3D splints were designed and printed in-house with polylactic acid from a 3D surface scan. Our data suggest that 3D-printed splinting is feasible, and patient satisfaction ratings were similar for 3D-printed and thermoplastic splints. The 3D splint production process needs to be optimized and other materials need to be tested before routine implementation is possible or more patients can be enrolled in further studies. Validated quality assessment tools for current splinting are lacking, and further investigation is necessary.