An in Vitro Assessment of Fibroblast and Osteoblast Response to Alendronate-modified Titanium and the Potential for Decreasing Fibrous Encapsulation

Fibrous encapsulation can impair implant osseointegration and cause implant failure but currently there are limited strategies to address this problem. Since bisphosphonates (BPs), a class of drugs widely used to treat bone diseases, was recently found to induce fibroblast apoptosis, we hypothesize that by loading BPs on titanium (Ti) implant surface, fibrous encapsulation may be inhibited with simultaneous enhancement of implant osseointegration. This strategy of local administration can also be expected to minimize the adverse side effects of BPs, which are associated with intravenous injections. To verify this hypothesis, alendronate was loaded on Ti surface via a hydroxyapatite (CaP) coating, and the effects of the loaded alendronate on fibroblast proliferation and apoptosis, and osteoblast proliferation, alkaline phosphatase (ALP) activity, and apoptosis were investigated in vitro. With a surface density of loaded alendronate 0.046 mg/cm(2) or higher, fibroblast proliferation was suppressed due to increased apoptosis, while osteoblast proliferation and ALP activity increased with minimal apoptosis. In a coculture of fibroblasts and osteoblasts in a 1:1 ratio, ~60% of the cells on these alendronate-loaded substrates were osteoblasts 1 day after cell seeding. The percentage of osteoblasts increased to about 75% 4 days after cell seeding. These results suggest that fibroblasts and osteoblasts respond differently toward the alendronate-modified substrates, and this phenomenon can potentially be capitalized to reduce fibrous encapsulation.