Osteoblast maturation and new bone formation in response to titanium implant surface features are reduced with age

The surface properties of materials contribute to host cellular response and play a significant role in determining the overall success or failure of an implanted biomaterial. Rough titanium (Ti) surface microtopography and high surface free energy have been shown to enhance osteoblast maturation in vitro and increase bone formation in vivo. Whereas the surface properties of Ti are known to affect osteoblast response, host bone quality also plays a significant role in determining successful osseointegration. One factor affecting host bone quality is patient age. We examined both in vitro and in vivo whether response to Ti surface features was affected by animal age. Calvarial osteoblasts isolated from 1-, 3-, and 11-month-old rats all displayed a reduction in cell number and increases in alkaline phosphatase-specific activity and osteocalcin in response to increasing Ti surface microtopography and surface energy. Further, osteoblasts from the three ages examined displayed increased production of osteocalcin and local factors osteoprotegerin, vascular endothelial growth factor (VEGF)-A, and active transforming growth factor (TGF)-β1 in response to increasing Ti surface roughness and surface energy. Latent TGF-β1 only increased in cultures of osteoblasts from 1- and 3-month-old rats. Treatment with the systemic osteotropic hormone 1α,25(OH)(2)D(3) further enhanced the response of osteoblasts to Ti surface features for all three age groups. However, osteoblasts derived from 11-month-old animals had a reduced response to 1α,25(OH)(2)D(3) compared to osteoblasts derived from 1- or 3-month-old animals. These results were confirmed in vivo. Ti implants placed in the femoral intramedullary canal of old (9-month-old) mice yielded lower bone-to-implant contact and neovascularization in response to Ti surface roughness and energy compared to younger (2-month-old) mice. These results show that rodent osteoblast maturation in vitro as well as new bone formation in vivo is reduced with age. Whether comparable age differences exist in humans needs to be determined.