Title

Application of calcium phosphate coating as drug delivery system for orthopedic implants

Date of Completion

January 2011

Keywords

Engineering, Materials Science

Degree

Ph.D.

Abstract

Musculoskeletal disorders are one of the most severe human health issues we have to face in the future due to the population aging in many countries. More than 1.1 million surgical procedures were performed in the USA and the estimated medical treatment for these patients is over 5 billion dollars. Although titanium and its alloys have been used as the dominant materials for orthopedic implants, they still suffer from shortcomings like limited life span and poor osseointegration. Biomimetic calcium phosphate (CaP) coatings improve the osteoconductivity of orthopedic implants and show promise as slow delivery systems for therapeutic proteins, therefore it is a promising approach to address the problems associated with titanium based implants. The objective of the proposed research plan is to fabricate a biomimetic CaP coating incorporating osteogenic agent on titanium based implant surface to improve the osseointegration of the titanium based implant. A systematical study was carried out using a model protein-bovine serum albumin (BSA) to reveal the mechanism of protein incorporation into CaP coating. The BSA incorporation efficiency has been improved by carefully adjusting the substrate surface area to simulated body fluid (SBF) volume ratio. Then, the release kinetics and release efficiency of BSA were optimized by changing the BSA adding time during the coating process. Parathyroid hormone (PTH), which is a potential bone growth stimulator, was chosen to be incorporated into biomimetic CaP coating as the osteogenic agent. The effect PTH incorporation into CaP coating on osteoblast adhesion, proliferation, and differentiation were evaluated using MC3T3-E1 cell culture. A mouse tibia insert model were further used to investigate the effect of PTH incorporated CaP coating on osseointegration of titanium implants. ^ The incorporation efficiency of BSA was substantially improved which makes it possible to lower the osteogenic agent cost. It is also demonstrated that the release kinetics of BSA from biomimetic CaP coating can be tailored by adjusting BSA adding time, therefore the release profile of osteogenic agent from CaP coating can be fit into its best therapeutic effectiveness. The concept demonstrated with model BSA is evident by PTH incorporation into the coating. PTH liberated from the coating remained its bioactivity and showed favorable influence on osteoblast proliferation. Animal study indicates that PTH incorporation into CaP coating can improve implant osseointegration in the mouse tibia. The biomimetic CaP coating bearing osteogenic agent could be a promising approach to improve titanium based implants' osseointegration and accelerate the bone healing process. ^