A CUSTOMIZABLE AUTOLOGOUS TISSUE ENGINEERING STRATEGY FOR BONE (RE)CONSTRUCTION

Symbrachydactyly is a rare congenital upper limb anomaly, that occurs in 1/30,000- 1/40,000 live births resulting in children born with short boneless fingers. In this project, we used adipose-derived stromal cells (ASC) from adult and pediatric donors in a developmentally-inspired strategy to engineer osteogenic grafts for phalanx construction via endochondral ossification (ECO). Human ASCs isolated from the stromal vascular fraction (SVF) were seeded first onto commercially available collagen sponges and exposed for two weeks to chondrogenic factors in vitro to generate individual cartilage spheres (10-60 mm 3 ) and then assembled and further cultured together to generate the grafts shaped as a phalanx. The bone forming capacity and biomechanical properties of these grafts was assessed in vitro and in vivo after implantation in an ectopic immunocompromised mouse model, reflecting the clinical scenario of phalangeal soft tissue pocket, for up to 24 weeks. In vitro , we were able to generate phalanx graft in cylindrical shape of clinically relevant sizes (length ranging from 6 to 14 mm width ranging from 2 to 5 mm) using adult and pediatric (15- to 24-month-old) donors. The presence of large pockets of cartilage tissues within the constructs was confirmed by histology. In vivo , we could observe an increase of the elastic modulus that was correlated with the increased mineralization. After 4 weeks of implantation, early signs of endochondral ossification were evidenced by the mineralization of the implanted cartilage tissues revealed by μCT. After 12 weeks of implantation, the bone remodeling was more advanced with an increase of the bone content and the presence of bone marrow pockets in the implanted constructs observed on histological sections. After 24 weeks some grafts fully remodeled in bone organs while preserving their size and Here we demonstrate the feasibility of an autologous approach using ASCs to generate osteogenic phalanx grafts for children born with symbrachydactyly. This project is partially funded by the Propatient Stiftung of the University Hospital of Basel.