Cartilaginous spheroid-assembly design considerations for endochondral ossification: towards robotic-driven biomanufacturing

Abstract Spheroids have become essential building blocks for biofabrication of functional tissues. Spheroid formats allow high cell-densities to be efficiently engineered into tissue structures closely resembling the native In this work, we explore assembly capacity cartilaginous spheroids ( d ? 150 µ m) in context endochondral bone formation. The fusion at various degrees differentiation was investigated and showed decreased kinetics as well remodeling with increased spheroid maturity. Subsequently, design considerations regarding dimensions spheroid-based mesotissues were explored corresponding time points, defining critical these type tissues they progressively mature. Next, mesotissue assemblies implanted subcutaneously order investigate influence parameters on ossification. Moreover, a step towards industrialization, demonstrated novel automated image-guided robotics process, based targeting registering single-spheroids, covering range work. This work highlights robust high-precision biomanufacturing roadmap producing implants regeneration.