Deconvoluting the Bioactivity of Calcium Phosphate-Based Bone Graft Substitutes: Strategies to Understand the Role of Individual Material Properties

Calcium phosphate (CaP)-based ceramics are the most widely applied synthetic biomaterials for repair and regeneration of damaged and diseased bone. CaP bioactivity is regulated by a set of largely intertwined physicochemical and structural properties, such as the surface microstructure, surface energy, porosity, chemical composition, crystallinity and stiffness. Unravelling the role of each individual property in the interaction between the biomaterial and the biological system is a prerequisite for evolving from a trial-and-error approach to a design-driven approach in the development of new functional biomaterials. This progress report critically reviews various strategies developed to decouple the roles of the individual material properties in the biological performance of CaP ceramics. It furthermore emphasizes on the importance of a comprehensive and adequate material characterization that is needed to enhance our knowledge of the property-function relationship of biomaterials used in bone regeneration, and in regenerative medicine in general.