Creation of Degradable Calcium/Phosphate Compounds Coated with Growth Factor-Containing Nanoparticles on Titanium Dental Implant Surfaces for Enhancing Osseointegration(3/3)

Sand-blasting/acid-etching surface treatment is one of the commonly used methods to promote the surface osseointegration of titanium (Ti) dental implant, which provides stable mechanical interlocking and good cell growth at the interface of implant/bone. However, the Ti surface modified by the abovementioned physical/chemical treatment is still bioinert. Thus, it is the future trend to develop the dental implant surface being able to initiatively induce the surrounding tissue growth. This project is to develop a new generation surface treatment of Ti dental implant. We will create a submicro-/micro-porous topography on Ti surfaces treated by sand-blasting/acid-etching process, followed by the electrochemical cathodic deposition process to create the degradable calcium phosphates with different solubilities by controlling the Ca/P ratio. The calcium phosphates include (1) tricalcium phosphate (TCP) with Ca/P ratio 1.5, (2) hydroxyapatite (HA) with Ca/P ratio 1.67 or (3) mixed TCP/HA compound with Ca/P ratio 1.5~1.67. Then, the Ca/P surfaces were coated with growth factor-containing gelatin nanoparticles. The nanoparticles carrying bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF) or BMP-2/VEGF mixture were designated NPs-B, NPs-V and NPs-BV, respectively. In this three-year project, we will evaluate the effects of surface treatments on Ti surface characters and the in vitro biological responses, including biocompatibility, human bone marrow mesenchymal stem cell (hMSC) response and human umbilical vein endothelial cell (HUVEC)] response. In the first year, different surface treatments will be applied to Ti surfaces, including (1) sand-blasting/acid-etching, (2) creation of calcium phosphates on sand-blasted/acid-etched surface and (3) creation of calcium phosphates on sand-blasted/acid-etched surface, followed by sequentially coating NPs-B, NPs-V and NPs-BV on calcium phosphates surface. Various surface characterizations, including morphology, chemical composition, functional group, roughness, wettability, coating stability and growth factor release, of the test specimens will be analyzed. In the second year, the ISO 10993 cytotoxicity assay, hMSC adhesion/proliferation/differentiation/mineralization and various protein expressions, including FAK and MAPK pathway's P38/ERK/JNK, during osseointegration process will be analyzed. In the third (last) year, the angiogenesis behavior of HUVEC and its related protein expressions, including Ang2, STAT3, Notch1, HIF-1, Akt/P13 and MAPK pathway's P38/ERK/JNK, will investigated. This project is expected to help boost the market for Taiwanese Ti dental implants surface treatment by enhancing international competitiveness.