Extensive early mineralization of pre-osteoblasts, inhibition of osteoclastogenesis and faster peri-implant bone healing in osteoporotic rat model: principle effectiveness of bone-specific delivery of Tibolone as evaluated in vitro and in vivo.

Hydrophobic drug molecules pose a significant challenge in immobilization on super-hydrophobic metallic surfaces like conventional titanium implants. Pre-coating surface modifications may yield a better platform with improved wettability for such purposes. Such modifications, as depicted in this study, were hypothesized to provide the requisite roughness to assist deposition of polymers like silk fibroin (SF) as a drug-binding matrix in addition to significant improvement in early protein adsorption, which facilitates faster cellular adhesion and proliferation. A silk-based localized drug delivery module was developed on the titanium surface and tested for its surface roughness, wettability, biocompatibility and in vitro differentiation potential of cells cultured on the coated metallic surfaces with/without external supplementation of the active metabolite of Tibolone. Conditioning of the matrix-coated implants with osteogenic as well as osteoclastogenic media supplemented with Tibolone stimulated the expression of early osteogenic gene and calcium deposition in the extracellular matrix. Significant inhibition in resorptive activity was also observed in the presence of the drug. To assess the efficacy of localized delivery of Tibolone via topographically modified titanium implants for inducing early peri-implant bone formation, osteoporosis was artificially induced in rats subjected to bilateral ovariectomy and implants were placed thereafter. Bone-specific release of Tibolone through the biomimetic matrix in osteoporotic rats collectively indicated significant improvement in peri-implant bone growth after 2 and 4 weeks (p < 0.05 compared to dummy-coated implants). These findings demonstrate for the first time that Tibolone released from SF matrix-coated implants can accelerate the biological stability of bone fixtures.