Ectopic bone formation using osteogenic protein-1 carried by a solution precipitated hydroxyapatite

Abstract

Solution precipitation of calcium and phosphate is a technique to generate hydroxyapatite [Peri‐Apatite™ (PA), Stryker Orthopaedics, Mahwah, NJ] on metal substrate. This study was carried out to determine the capacity of PA to adsorb osteogenic protein‐1 (OP‐1) and the time course of release, and to determine the osteoinductive activity of OP‐1. The adsorption and release studies were conducted with ¹²⁵I‐labeled OP‐1– and PA‐coated titanium alloy disks. The results indicate that the adsorption of OP‐1 on the PA‐coated disks is linear with the concentration of OP‐1 up to 5 mg/mL. There is an initial release of 75% to 80% of adsorbed OP‐1 within the first hour, and 92% of OP‐1 is released in 3 days. The osteoinductive activity of OP‐1 was determined in the rat intramuscular ectopic bone formation assay. A total of 24 titanium alloy disks were evenly divided into 3 groups with different treatments for implantation, plain disks (group A), disks coated with PA (group B), and disks coated with PA plus 40 μg OP‐1 (group C). Osteogenic protein‐1, 40 μg in solution, was injected into the muscle pouch in animals of group D (n = 8). The rats were sacrificed 3 weeks postoperatively and the implants were retrieved. Ectopic bone formation was evaluated with radiography and histology. Results demonstrated that OP‐1 induced ectopic bone in all the animals of group C and group D. The titanium alloy disks were surrounded by trabecular bone and marrow tissue. None of the animals of group A or group B showed any evidence of osteoinduction. Our findings indicate that PA can deliver OP‐1 directly to titanium alloy implants and maintain the osteoinductive activity of OP‐1. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 71A: 412–418, 2004