Biomaterials 27 (2006) 4934–4940 Repair of long intercalated rib defects using porous beta-tricalcium phosphate cylinders containing recombinant human bone morphogenetic protein-2 in dogs Masatoshi Hoshino a,Ã , Takeshi Egi b , Hidetomi Terai a , Takashi Namikawa a , Kunio Takaoka a a Department of Orthopedic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-Machi, Abeno-Ku, Osaka 545-8585, Japan b Department of Rheumatology, Higashisumiyoshi Morimoto Hospital, 3-2-66 Takaai, Higashisumiyoshi-ku, Osaka 546-0014, Japan Received 3 February 2006; accepted 28 April 2006 Available online 6 June 2006 Abstract A new method to repair rib defects with biomaterials containing recombinant human bone morphogenetic protein-2 (rhBMP-2) is presented in this report. We had reported previously the successful regeneration of bony rib defects by placing a short chain of small beta-tricalcium phosphate (b-TCP) cylinders on the intact periosteum. The multi-cylinder implants were ineffective in promoting rib repair when the periosteum was absent. By adding rhBMP-2 to the b-TCP cylinders, we were able to promote rib bone regeneration in the presence or absence of the periosteum. The osteogenic capacity of the rhBMP-2/b-TCP composite implant and the time required to complete regeneration were evaluated in a canine model. An 8 cm long section of rib bone, including the periosteum, was removed and replaced with a chain of the rhBMP-2/b-TCP cylinders. At 6 weeks after implantation, the ribs were restored to their original configuration and mechanical strength. The multi-cylinder b-TCP implants were degraded and replaced by new bone in 12 weeks. This new degradable bone-inducing implant material has significant clinical potential for rib repair. r 2006 Elsevier Ltd. All rights reserved. Keywords: Bone regeneration; Bone morphogenetic protein (BMP); Calcium phosphate; Biodegradation 1. Introduction Intercalated rib defects are often created as a result of the excision of tumors located in ribs or the soft tissue of the thoracic cage [1]. Additionally, the harvesting of bone for grafting in situations such as spinal fusion also leads to rib defects [2]. Currently, rib defects are left unrepaired because they have little impact on respiratory function and there is no clear robust method for rib regeneration. However, the risks for physical and cosmetic morbidities associated with the resection or loss of the ribs are significant and include chronic pain, deformity and paradoxical respiratory motion of the thoracic cage [3,4]. A few types of rib prostheses have been used to preserve respiratory function although concerns persist with infection risk and clinical efficacy due to the limited biocompatibility and osteogenic potential of the prosthesis [5,6]. In our previous study, rib defects produced in dog were successfully repaired by implanting small cylinders of the biocompatible, osteo-conductive biodegradable bioma- terial, beta-tricalcium phosphate (b-TCP), placed in tandem on the intact periosteum. Rib regeneration occurred within 12 weeks when the periosteum was present but was unsuccessful when absent, thus indicating that the presence of intact periosteum was essential for rib replacement using osteoconductive implants [7]. To address this problem, we combined an osteo- inductive agent, recombinant human bone morphogenetic protein-2 (rhBMP-2) with the porous b-TCP implants. The efficacy of the new implants was investigated in terms of osteogenic capacity and time required to complete bone regeneration in a canine rib defect model described previously [7]. ARTICLE IN PRESS www.elsevier.com/locate/biomaterials 0142-9612/$ - see front matter r 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.biomaterials.2006.04.044 Ã Corresponding author. Tel.: +81 6 6645 3851; fax: +81 6 6646 6260. E-mail address: hirotoy@msic.med.osaka-cu.ac.jp (M. Hoshino).