Controlled Delivery of Curcumin and Vitamin K2 from Hydroxyapatite-Coated Titanium Implant for Enhanced in Vitro Chemoprevention, Osteogenesis, and in Vivo Osseointegration.

Successful repair of critical-sized tumor-resection defects, especially in load-bearing bones, still remains a major challenge in clinical orthopedics. Titanium (Ti) implants have been increasingly used in the past few decades because of titanium's suitable mechanical properties and biocompatibility; however, it shows insufficient integration with the surrounding bone. In this study, the plasma spray technique is utilized to form homogeneous hydroxyapatite (HA) coating on the surface of the Ti implant to enhance osseointegration at the tissue-implant interface. These coated implants are loaded with curcumin and vitamin K2 to introduce chemopreventive and osteogenesis ability via controlled release of these biomolecules. The synergistic effect of these two biomolecules showed enhanced in vitro osteoblast (hFOB) cell attachment and proliferation for 11 days. Moreover, these biomolecules showed lower in vitro osteosarcoma (MG-63) cell proliferation after 3, 7, and 11 days. An in vivo study was carried out to evaluate the bone bonded zone in a rat distal femur model at an early wound healing stage of 5 days. Modified Masson Goldner staining of the tissue-implant section showed improved contact between tissue and implant in dual drug-loaded HA-coated Ti implants compared to control implants. This work presents a successful fabrication of a mechanically competent functional Ti implant with the advantages of enhanced in vitro osteoblast proliferation, osteosarcoma inhibition, and in vivo osseointegration, indicating the potential for load-bearing bone-defect repair after tumor resection.