Stem cell behavior and biomaterials Implications for oral regenerative medicine

Bone tissue engineering has become a promising alternative for the use of autologous bone in the reconstruction of bone defects in oral regenerative medicine. The main goal of this thesis was to investigate behavior of human adipose stem cells (hASCs) and fibroblasts in/on resin-based composites, natural polymer fibrin, and ceramic biphasic calcium phosphate (BCP). We found different mechanoresponsiveness of hASCs on nanocomposite and micro-hybrid composite, which is important for materials used to fixate dental implants or close bone defects. Our observed adaptation of fibrin to cell-generated contractile stresses might improve wound healing in maxillary sinus floor elevation. Efficient scaffold remodeling requires a BCP with an optimum ratio of hydroxyapatite (HA) and ß-tricalcium phosphate (ß-TCP). We found enhanced osteogenic and vasculogenic differentiation potential of hASCs on BCP with a HA/ß-TCP ratio of 20/80 (BCP20/80) compared to hASCs on BCP60/40, both in fibrin gel. Under hypoxia, decreased osteogenic differentiation potential, but enhanced vasculogenic differentiation potential of BCP60/40- and BCP20/80-based composites were observed. Patients undergoing maxillary sinus floor elevation treated with BCP20/80 showed enhanced osteogenic differentiation potential compared to BCP60/40.
These results suggest that BCP20/80 and BCP20/80-based composites might result in sprouting and tube formation leading to increased cell survival and stimulation of bone formation, and might be more promising for in vivo bone augmentation than BCP60/40 and BCP60/40-based composites. This will have pivotal implications for bone tissue engineering in oral regenerative medicine. Since stem cell-based composites stimulated osteogenesis and angiogenesis, patients worldwide could benefit from these composites for reconstruction of bone defects.