Manipulating calcium phosphate materials with surface topography for bone regeneration

This thesis was aimed to explore the crucial material parameters involved in material-instructed bone formation and which material factors trigger bone formation, to study the possible biological mechanism underneath material-instructed bone formation and to evaluate the bone regeneration capacities of osteoinductive calcium phosphate materials in clinically relevant animal models.

Throughout this thesis, the overarching findings were 1) submicron scaled surface topography was a crucial material factor to initiate material-instructed bone formation in ectopic sites; 2) rather than protein adsorption, ion release and biomineralization, surface topography played its role in material-instructed bone formation by its physical cues; 3) the physical cues provided by surface topography may not directly differentiate mesenchymal stem to form bone but first affect the macrophage phenotype which are coupled with angiogenesis and bone formation; 4) either alone or in a moldable putty when combined with polymeric carriers, the materials with specific surface topography not only induced bone formation following ectopic implantation but also enhanced regeneration in orthopedic sites and could performed equivalently to autograft in clinically relevant bone regeneration models; 5) moreover, next to the dimension, surface morphology was another physical parameter playing roles in material-instructed bone formation and osteoinductive potential could be further improved with the needle-shaped surface feature.

The overall data presented in this thesis give more insights on material mechanism and biological mechanism of material-instructive bone formation, and pave a way for further improvement of bone substitutes and the clinical applications of such bone substitutes with improved bone forming ability.