New enhancing method of osteogenesis by using nanocarrier-fused BMP-4
May 27, 2013
Researchers from the Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences have succeeded in promoting bone regeneration by using without a scaffold at a localized site an engineered bone morphogenetic protein-4 (BMP-4) that has the ability to bind to collagen.
Treatment of bone defects and nonunions that are caused by bone tumors and bone trauma is mainly done with autogenous bone grafting. However, there are many problems with grafting. This includes limits on the shape and size of the harvested bone, as well as pain, fractures, or neural damage at the site where bone was harvested.
This new method could develop a new treatment that does not use autogenous grafting by instead using fused BMP-4 that is retained locally for a long period.
The findings were published online April 9 in the journal Nanomedicine.
http://www.ncbi.nlm.nih.gov/pubmed/23630418
A. Matsukawa, T. Ozaki and their colleagues in the collaborative research group of Okayama University and RIKEN (Wako campus) have engineered a bone morphogenetic protein-4 fused with a nanosized carrier, collagen-binding domain (CBD-BMP4). In vivo, CBD-BMP4 was retained at the given site for a long period of time and enhanced bone formation.
2 kinds of BMP (BMP2 and BMP7/OP1) have cleared by FDA in the US; for BMP2 in particular, clinical applications of it in the field of orthopedics are becoming more frequent. However, BMP2 is not retained locally; as a result, ectopic ossification occurs. The group demonstrated that while BMP4 disappeared from the given site within three days, CBD-BMP4 that has the ability to bind to collagen remained at the site for at least two weeks. Normally, BMP is injected with a collagen-sponge scaffold.
When applied into bone marrow and cranial bone defect sites in mice, CBD-BMP4 induced better bone formation by enhancing the expression of bone-related genes than BMP4 did alone.
The study is highly praised for showing to induce bone formation with the fused protein alone without a scaffold such as a collagen sponge for the first time.
It is important that bone morphogenetic factor is retained locally for a long time and prevented from diffusion in order to increase the effectiveness of the treatment. The group focused on collagen, a major component of bone tissue, and used a fusion protein consisting of CBD that has the ability to bind to collagen and MBP4 for the treatment. This treatment achieved bone induction with an unprecedented low dose of BMP4（≈ 2pM）. In contrast, the conventional treatment is 2.5-5 micro-gram of BMP4 injection with collagen sponge.
Contact Information:
Mototaka Senda, Ph.D.
Intellectual Property Office, Organization for Research Promotion and Collaboration
US Representative, Fremont, California USA
TEL: 1-510-797-0907
Email: [email protected]
Akihiro Matsukawa, Ph.D
Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan