A biodegradable polymer as a cytokine delivery system for inducing bone formation 

Nature Biotechnology v.19, n.4 pp 332-335 Apr01

Naoto Saito¹, Takao Okada², Hiroshi Horiuchi¹, Narumichi Murakami¹, Jun Takahashi¹, Masashi Nawata¹, Hiroshi Ota¹, Kazutoshi Nozaki³ & Kunio Takaoka¹

1. Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
2. Research Institute, Taki Chemical Co., Ltd., 64-1 Nishiwaki, Befucho, Kakogawa, Hyogo 675-0125, Japan.
3. Applied Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.

Correspondence should be addressed to N Saito. e-mail: saitoko@hsp.md.shinshu-u.ac.jp

Bone morphogenetic proteins (BMPs) that have the potential to elicit new bone in vivo have been used in a tissue-engineering approach for the repair of bone injuries and bone defects. Although it is now possible to generate large amounts of recombinant human (rh) BMPs for medical use, the major challenge remains in the development of optimal local delivery systems for these proteins. Here we describe the development of a synthetic biodegradable polymer, poly-D,L-lactic acid–p-dioxanone–polyethylene glycol block copolymer (PLA-DX-PEG). This polymer exhibits promising degradation characteristics for BMP delivery systems and good biocompatibility under test conditions. PLA-DX-PEG/rhBMP-2 composite implants induced ectopic new bone formation effectively when tested in vivo, and can repair large bone defects orthotopically. This polymeric delivery system represents an advance in the technology for the enhancement of bone repair.