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

Subscribe to this journal Receive 12 print issues and online access $209.00 per year only $17.42 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full

article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs *

Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS A NOVEL BMP-2–LOADED HYDROXYAPATITE/BETA-TRICALCIUM PHOSPHATE MICROSPHERE/HYDROGEL COMPOSITE FOR BONE REGENERATION Article

Open access 19 August 2021 AN ENGINEERED PERIOSTEUM FOR EFFICIENT DELIVERY OF RHBMP-2 AND MESENCHYMAL PROGENITOR CELLS DURING BONE REGENERATION Article Open access 29 September 2023 ENHANCED

BONE REGENERATION IN RAT CALVARIAL DEFECTS THROUGH BMP2 RELEASE FROM ENGINEERED POLY(ETHYLENE GLYCOL) HYDROGELS Article Open access 28 February 2024 REFERENCES * Einhorn, T.S. Enhancement

of fracture-healing. _J. Bone Joint Surg. Am._ 77, 940–956 (1995). Article  CAS  Google Scholar  * Tomford, W.W. Transmission of disease through transplantation of musculoskeletal

allografts. _J. Bone Joint Surg. Am._ 77, 1742–1754 (1995). Article  CAS  Google Scholar  * Urist, M.R. Bone formation by autoinduction. _Science_ 150, 893–899 (1965). Article  CAS  Google

Scholar  * Reddi, A.H. Symbiosis of biotechnology and biomaterials: application in tissue engineering of bone and cartilage. _J. Cell. Biochem._ 56, 192–195 (1994). Article  CAS  Google

Scholar  * Reddi, A.H. BMPs: actions in flesh and bone. _Nat. Med._ 3, 837–839 (1997). Article  CAS  Google Scholar  * Schmitt, J.M., Hwang, K., Winn, S.R. & Hollinger, J.O. Bone

morphogenetic proteins: an update on basic biology and clinical relevance. _J. Orthop. Res._ 17, 269–278 (1999). Article  CAS  Google Scholar  * Fang, J. et al. Stimulation of new bone

formation by direct transfer of osteogenic plasmid gene. _Proc. Natl. Acad. Sci. USA_ 93, 5753–5758 (1996). Article  CAS  Google Scholar  * Bonadio, J., Smiley, E., Patil, P. &

Goldstein, S. Localized, direct plasmid gene delivery _in vivo_: prolonged therapy results in reproducible tissue regeneration. _Nat. Med._ 5, 753–759 (1999). Article  CAS  Google Scholar  *

Caplan, A.I. Mesenchymal stem cells. _J. Orthop. Res._ 9, 641–650 (1991). Article  CAS  Google Scholar  * Wozney, J.M. et al. Novel regulators of bone formation: molecular clones and

activities. _Science_ 242, 1528–1533 (1988). Article  CAS  Google Scholar  * Wang, E.A. et al. Recombinant human bone morphogenetic protein induces bone formation. _Proc. Natl. Acad. Sci.

USA_ 87, 2220–2224 (1990). Article  CAS  Google Scholar  * Hollinger, J.O. & Leong, K. Poly(_-hydroxy acids): carriers for bone morphogenetic proteins. _Biomaterials_ 17, 187–194 (1996).

Article  CAS  Google Scholar  * Takaoka, K., Koezuka, M. & Nakahara, H. Telopeptide-depleted bovine skin collagen as a carrier for bone morphogenetic protein. _J. Orthop. Res._ 9,

902–907 (1991). Article  CAS  Google Scholar  * Rodeo, S.A., Suzuki, K., Deng, X., Wozney, J. & Warren, R.F. Use of recombinant bone morphogenetic protein-2 to enhance tendon healing in

a bone tunnel. _Am. J. Sports Med._ 27, 476–488 (1999). Article  CAS  Google Scholar  * DeLustro, F., Dasch, J., Keefe, J. & Ellingsworth, L. Immune responses to allogeneic and

xenogeneic implants of collagen and collagen derivatives. _Clin. Orthop._ 260, 263–279 (1990). Article  Google Scholar  * Butler, D., Wadman, M., Lehrman, S. & Schiermeier, Q. Last

chance to stop and think on risks of xenotransplants. _Nature_ 391, 320–324 (1998). CAS  PubMed  Google Scholar  * Bach, F.H. et al. Uncertainty in xenotransplantation: individual benefit

versus collective risk. _Nat. Med._ 4, 141–144 (1998). Article  CAS  Google Scholar  * Miyamoto, S. et al. Evaluation of polylactic acid homopolymers as carriers for bone morphogenetic

protein. _Clin. Orthop._ 278, 274–285 (1992). Google Scholar  * Kenley, R. et al. Osseous regeneration in the rat calvarium using novel delivery systems for recombinant human bone

morphogenetic protein-2 (rhBMP-2). _J. Biomed. Mater. Res._ 28, 1139–1147 (1994). Article  CAS  Google Scholar  * Zegzula, H.D., Buck, D.C., Brekke, J., Wozney, J.M. & Hollinger, J.O.

Bone formation with use of rhBMP-2 (recombinant human bone morphogenetic protein-2). _J. Bone Joint Surg. Am._ 79, 1778–1790 (1997). Article  CAS  Google Scholar  * Miyamoto, S. et al.

Polylactic acid–polyethylene glycol block copolymer: a new biodegradable synthetic carrier for bone morphogenetic protein. _Clin. Orthop._ 294, 333–343 (1993). Article  Google Scholar  *

Saito, N., Okada, T., Toba, S., Miyamoto, S. & Takaoka K. New synthetic absorbable polymers as BMP-carriers: plastic properties of poly-D,L-lactic acid-polyethylene glycol block

copolymers. _J. Biomed. Mater. Res._ 47, 104–110 (1999). Article  CAS  Google Scholar  * Langer, R. New methods of drug delivery. _Science_ 249, 1527–1533 (1990). Article  CAS  Google

Scholar  * Langer, R. Drug delivery and targeting. _Nature_ 392, 5–10 (1998). CAS  PubMed  Google Scholar  * Boyne, P.J. et al. A feasibility study evaluating rhBMP-2/absorbable collagen

sponge for maxillary sinus floor augmentation. _Int. J. Periodont. Rest. Dent._ 17, 11–26 (1997). CAS  Google Scholar  * Geesink, R.G., Hoefnagels, N.H.M. & Bulstra, S.K. Osteogenic

activity of OP-1 bone morphogenetic protein (BMP-7) in a human fibular defect. _J. Bone Joint Surg. Br._ 81, 710–718 (1999). Article  CAS  Google Scholar  * Zhu, K.J., Xiangzhou, L. &

Shilin, Y. Preparation, characterization and properties of polylactide (PLA)–poly(ethylene glycol) (PEG) copolymers: a potential drug carrier. _J. Appl. Polym. Sci._ 39, 1–9 (1990). Article

  CAS  Google Scholar  * Jeong, B., Bae, Y.H., Lee, D.S. & Kim, S.W. Biodegradable block copolymers as injectable drug-delivery systems. _Nature_ 388, 860–862 (1997). Article  CAS 

Google Scholar  * Ray, J.A., Doddi, N., Regula, D., Williams, J.A. & Melveger, A. Polydyoxanone (PDS), a novel monofilament synthetic absorbable suture. _Surg. Gynecol. Obstet._ 153,

497–507 (1981). CAS  PubMed  Google Scholar  Download references 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. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of

Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Nagano, Japan Naoto Saito, Hiroshi Horiuchi, Narumichi Murakami, Jun Takahashi, Masashi Nawata, 

Hiroshi Ota & Kunio Takaoka * Research Institute, Taki Chemical Co., Ltd., 64-1 Nishiwaki, Befucho, Kakogawa, 675-0125, Hyogo, Japan Takao Okada * Applied Pharmacology Laboratories,

Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, 305-8585, Ibaraki, Japan Kazutoshi Nozaki Authors * Naoto Saito View author publications

You can also search for this author inPubMed Google Scholar * Takao Okada View author publications You can also search for this author inPubMed Google Scholar * Hiroshi Horiuchi View author

publications You can also search for this author inPubMed Google Scholar * Narumichi Murakami View author publications You can also search for this author inPubMed Google Scholar * Jun

Takahashi View author publications You can also search for this author inPubMed Google Scholar * Masashi Nawata View author publications You can also search for this author inPubMed Google

Scholar * Hiroshi Ota View author publications You can also search for this author inPubMed Google Scholar * Kazutoshi Nozaki View author publications You can also search for this author

inPubMed Google Scholar * Kunio Takaoka View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Naoto Saito. RIGHTS AND

PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 27 November 2000 * Accepted: 31 January 2001 * Issue Date: April 2001 * DOI:

https://doi.org/10.1038/86715 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently

available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative