Functionalization of a clustered TiO2 nanotubular surface with platelet derived growth factor-BB covalent modification enhances osteogenic differentiation of bone marrow mesenchymal stem cells

A multitude of micro- and nano-surface structures have been developed to improve the clinical performance of endosseous titanium (Ti) implants. However, most of these surface structures only simulate the topographic elements on a micro- or nano-scale. In this study, a nano-micro hierarchical TiO2 clustered nanotubular structure was fabricated using anodization, and then functionalized with platelet derived growth factor-BB (PDGF-BB) using PhoA (11-hydroxyundecylphosphonic acid)/CDI (carbonyldiimidazole) chemistry. The resulting 3-dimensional spatial biomimetic structure, named NTPCP, exhibited negligible cytotoxicity and satisfactory bio-activity for host cells, and significantly enhanced the attachment as well as osteogenesis-related functions (early-stage proliferation, extracellular matrix synthesis and mineralization) of human bone marrow mesenchymal stem cells (bMSCs). We observed drastically elevated expression of osteocalcin (OCN), which mirrored prominent bone formation around the NTPCP implants in a rat model. This study establishes a novel strategy to improve the osseointegration of endosseous Ti implants via surface nano-topographic modification and bio-factor covalent functionalization.