Scaffolded Spheroids: A New Strategy for Osteochondral Tissue Engineering

Multicellular aggregates, also referred to as spheroids or pellets, have become increasingly popular as building blocks for tissue engineering (TE) . They show improved biological properties with regard to regenerative capacity and provide a route to generating tissue constructs with high initial cell density. Nevertheless, the use of such building blocks also comes with substantial challenges - prolonged culture of spheroids often results in rather inhomogeneous size and shape distribution, while their compaction and fusion can lead to substantial volume loss. We have recently introduced a novel synergetic TE strategy enabled by the use of 3D printed microscaffolds, which allows to solve these issues. The specialized microscaffolds help to reduce the compaction of the individual spheroids that they are hosting, as well as maintain their shape and roundness over extended cell culture periods. Scaffolded spheroids show high viability and preserve chondrogenic and osteogenic potential of human adipose-derived stem cells (ASCs). They were successfully used for bottom-up assembly of larger tissue constructs. Furthermore, it was demonstrated that the presence of microscaffolds improves the fusiogenic capacity of spheroids differentiated towards chondrogenic lineage and characterized by substantial deposition of according extra-cellular matrix (ECM). Our findings indicate that the microscaffolds carrying high density of cells are promising building blocks for cartilage and bone TE. This synergetic approach provides a route towards recreating more complex tissues by combining scaffolded spheroids differentiated towards different phenotypes, as demonstrated on the example of osteo-chondral construct. In this contribution our recent progress, as well as perspectives for further TE applications of scaffolded spheroids, will be discussed.