UBC Theses and Dissertations
Bisphosphonate-containing coatings for bone implants Duan, Ke
Bone implants are extensively used to replace joints affected by skeletal problems. Challenges remain to further improve the clinical outcomes of implants. A fast and strong implant fixation would improve the patient's quality of life and reduce implant failure risk. The service life of implants needs to be extended, particularly for the younger patients. A logical approach to these challenges is to control the peri-implant bone formation and remodeling. Bisphosphonate drugs, potent osteoclast inhibitors, are the appropriate choice for this purpose. This thesis studied bisphosphonate-containing coatings on bone implants for local drug delivery. A reproducible electrolytic deposition (ELD) process was developed to prepare calcium phosphate (CaP) coatings on Ti and Ta as bisphosphonate carrier. The ELD parameters were experimentally determined. Microporous coatings containing octacalcium-phosphate were obtained; the pore sizes were 0.5-1 μm. The ELD current showed a rapid Cottrell-type decay followed by a prolonged nearly-constant stage, corresponding to proton reduction and molecular water electrolysis, respectively. Alendronate was chemically adsorbed on the CaP coating, and the in vitro release from the coated porous Ta implant was slow, with ~10% released after 7 days. The ELD technique was extended to process solid bisphosphonate coatings. Uniform coatings of calcium-etidronate and calcium-alendronate were deposited on Ti and porous Ta. The ELD process did not alter the molecular structures of the bisphosphonates. The solubility of the coatings in a "physiological" buffer solution was 6 x 10⁻⁵ M for Ca-etidronate and 2.5 x 10⁻⁴ M for calcium alendronate. In vitro release of alendronate from the calcium-alendronate-coated porous Ta was completed within 3 days, and the alendronate concentration was below the solubility limit. To evaluate the in vivo performance, porous Ta implants coated with the bisphosphonate-containing coatings were implanted into rabbit tibial diaphyses together with control implants. Four weeks after implantation, the CaP-coated implants with chemically adsorbed alendronate showed significantly higher total new bone area and pushout strength. The implants with calcium alendronate solid coating showed similar implant fixation and new bone area to the native Ta implants. Eight weeks after implantation, the differences in push-out strength and total new bone area were not significant among different implants.
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