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.

Bioprinting of Stable Bionic Interfaces Using Piezoresistive Hydrogel Organoelectronics.

Bionic tissues offer an exciting frontier in biomedical research by integrating biological cells with artificial electronics, such as sensors. One critical hurdle is the development of artificial electronics that can mechanically harmonize with biological tissues, ensuring a robust interface for effective strain transfer and local deformation sensing. In this study, a highly tissue-integrative, soft mechanical sensor fabricated from a composite piezoresistive hydrogel. The composite not only exhibits exceptional mechanical properties, with elongation at the point of fracture reaching up to 680%, but also maintains excellent biocompatibility across multiple cell types. Furthermore, the material exhibits bioadhesive qualities, facilitating stable cell adhesion to its surface. A unique advantage of the formulation is the compatibility with 3D bioprinting, an essential technique for fabricating stable interfaces. A multimaterial sensorized 3D bionic construct is successfully bioprinted, and it is compared to structures produced via hydrogel casting. In contrast to cast constructs, the bioprinted ones display a high (87%) cell viability, preserve differentiation ability, and structural integrity of the sensor-tissue interface throughout the tissue development duration of 10 d. With easy fabrication and effective soft tissue integration, this composite holds significant promise for various biomedical applications, including implantable electronics and organ-on-a-chip technologies.