Topography as a cue for driving osteochondral unit regeneration

Osteochondral defects are injuries generally affecting to the surface of hyaline cartilage and progressing throughout the tissue until the underlying subchondral bone. The osteochondral unit is a multi-zonal tissue in which cells within each layer have a specific phenotype arising from their differential maturation stages; persistent, proliferative and hypertrophic chondrocytes in the superficial, middle and deep zones of cartilage, respectively, and osteoblast in the subchondral bone. These distinct cells regulate the composition of their microenvironment through sensing the surrounding physicochemical properties, where topography plays a crucial role. Tissue regeneration appears as a great alternative to promote the formation of a durable and functional osteochondral unit, where distinct parameters such as the biomaterial chemistry, mechanical properties or topography can be adjusted to match the native tissue. However, current approaches focus mainly on tuning the first two parameters, omitting the inclusion of topography. Moreover, only few have considered the inclusion of topography on scaffolds and investigated their effect in pre-clinical studies; number that is further reduced when reaching clinical trials. This review summarizes the state of the art in the regeneration of the osteochondral unit through the exploitation of topographical cues, setting into context relevant biological aspects, such as cell adhesion and proliferation, phenotype and deposition of zone-specific extracellular matrix that lead to the formation of a functional tissue.