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

Abstract

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.

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Figure 1: Structural formula of poly-D,L-lactic acid–p-dioxanone–polyethylene glycol block copolymer (PLA-DX-PEG).
Figure 2: Loss of mass as a function of degradation time for the 9.5K-PLA-DX-PEG and the 9.5K-PLA-PEG polymers in vitro.
Figure 3: Swelling ratio of the 9.5K-PLA-DX-PEG or the 9.5K-PLA-PEG polymer as a function of time in vitro.
Figure 4: A soft x-ray photograph and light micrograph of the new bone formed three weeks after implantation in the 9.5K-PLA-DX-PEG implant with 10 μg of rhBMP-2.
Figure 5: The calcium content of the induced bone by the 9.5K-PLA-DX-PEG–rhBMP-2 composites and the collagen–rhBMP-2 composites.
Figure 6: Repair of large bone defects in rat ilia by 9.5K-PLA-DX-PEG/rhBMP-2 composite implants.

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Acknowledgements

This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture, Japan, a grant from the Japan Rheumatism Foundation, and a grant from the Hip Joint Foundation of Japan.

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Correspondence to Naoto Saito.

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Saito, N., Okada, T., Horiuchi, H. et al. A biodegradable polymer as a cytokine delivery system for inducing bone formation. Nat Biotechnol 19, 332–335 (2001). https://doi.org/10.1038/86715

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