Enhancing bone regeneration by calcium phosphates with surface topography: A translational evaluation of synthetic bone graft substitutes

The overall aim of this thesis was to determine if and how topography of calcium phosphates can be improved for increased efficacy as bone graft materials for maxillofacial and orthopedic surgery. To achieve this objective, we manufactured calcium phosphate bone grafts with different surface designs, i.e. topographies with different surface crystal morphology (needle-shaped vs. grain-shaped) in the micron- and submicron range, and evaluated their ability to induce ectopic bone formation in a canine intramuscular pouch model. The material with the highest osteoinductive potential, attributed to its needle-shaped submicron topography, was selected for further evaluation in pre-clinical models of orthopedic surgery (i.e. spinal fusion) and maxillofacial surgery (i.e. maxillary sinus floor augmentation). In these studies, the material was compared to the gold standard autograft and/or other synthetic bone graft substitute materials. In addition to these pre-clinical studies, the bone graft material with needle-shaped topography was evaluated in a retrospective cohort study of interbody spinal fusion and a preliminary prospective, randomized controlled trial (RCT) of maxillary sinus floor augmentation. Furthermore, to gain insight into the biological effects of calcium phosphate topography, polarization of primary human macrophages in response to calcium phosphates with submicron needle-shaped topography and conventional topography was assessed in vitro, which included an evaluation of downstream regenerative effects of macrophages on osteogenesis and angiogenesis. These findings were placed in perspective of the available literature, in a review of M2 macrophage upregulation by biomaterials with specific structural and topographical features