Mimetic Hierarchical Approaches for Osteochondral Tissue Engineering.

In order to engineer biomimetic osteochondral (OC) construct, it is necessary to address both the cartilage and bone phase of the construct, as well as the interface between them, in effect mimicking the developmental processes when generating hierarchical scaffolds that show gradual changes of physical and mechanical properties, ideally complemented with the biochemical gradients. There are several components whose characteristics need to be taken into account in such biomimetic approach, including cells, scaffolds, bioreactors as well as various developmental processes such as mesenchymal condensation and vascularization, that need to be stimulated through the use of growth factors, mechanical stimulation, purinergic signaling, low oxygen conditioning, and immunomodulation. This chapter gives overview of these biomimetic OC system components, including the OC interface, as well as various methods of fabrication utilized in OC biomimetic tissue engineering (TE) of gradient scaffolds. Special attention is given to addressing the issue of achieving clinical size, anatomically shaped constructs. Besides such neotissue engineering for potential clinical use, other applications of biomimetic OC TE including formation of the OC tissues to be used as high-fidelity disease/healing models and as in vitro models for drug toxicity/efficacy evaluation are covered.

HIGHLIGHTS: Biomimetic OC TE uses "smart" scaffolds able to locally regulate cell phenotypes and dual-flow bioreactors for two sets of conditions for cartilage/bone Protocols for hierarchical OC grafts engineering should entail mesenchymal condensation for cartilage and vascular component for bone Immunomodulation, low oxygen tension, purinergic signaling, time dependence of stimuli application are important aspects to consider in biomimetic OC TE.