There is a recognized need to develop and field clinical therapeutics to regenerate bone in the orofacial complex. The investigators have assembled an experienced multidisciplinary team focused on developing and fielding a bone regenerative therapeutic composite of recombinant human bone morphogenetic protein-2 (rhBMP-2), osteoblast precursor cells (OPCs), and """"""""smart"""""""" polymer delivery system (SPS). Developing and optimizing the therapeutic composite will involve a staged set of experimental in vitro and in vivo models culminating in validation of clinical efficacy in the rhesus. Moreover, consistent with the growth in the nation's geriatric population, the investigators will include a geriatric cohort. The proposed study has been formulated to address design and preclinical evaluations of the therapeutic composite and individual component interactions on orofacial bone regeneration. Therefore, overall specific aims will include the fabrication of a """"""""smart"""""""" polymer delivery system (SPS) for rhBMP-2 and OPCs; development and characterization of dog- and rhesus-derived OPCs and genetic modification of these cells as well as human OPCs to express BMP-2; and validation of therapeutic efficacy of the rhBMP-2/OPC/SPS composite to regenerate orofacial bone in adult dog and adult and geriatric nonhuman primates. The general hypothesis is that predictable bone regeneration can be accomplished with the uniquely engineered composition. The composition will be administered to mandibular continuity defects to test the general hypothesis and analyses will involve clinical and morphometric methodologies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE013018-02
Application #
2897235
Study Section
Special Emphasis Panel (ZHL1-CSR-F (M2))
Program Officer
Panagis, James S
Project Start
1998-09-01
Project End
2000-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Surgery
Type
Schools of Medicine
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239
Gruber, Reinhard; Koch, Hannjorg; Doll, Bruce A et al. (2006) Fracture healing in the elderly patient. Exp Gerontol 41:1080-93
Fu, Huihua; Hu, Yunhua; McNelis, Tim et al. (2005) A calcium phosphate-based gene delivery system. J Biomed Mater Res A 74:40-8
Hu, Yunhua; Winn, Shelley R; Krajbich, Ian et al. (2003) Porous polymer scaffolds surface-modified with arginine-glycine-aspartic acid enhance bone cell attachment and differentiation in vitro. J Biomed Mater Res A 64:583-90
Jadlowiec, Julie A; Celil, Ayse B; Hollinger, Jeffrey O (2003) Bone tissue engineering: recent advances and promising therapeutic agents. Expert Opin Biol Ther 3:409-23
Hu, Yunhua; Grainger, David W; Winn, Shelley R et al. (2002) Fabrication of poly(alpha-hydroxy acid) foam scaffolds using multiple solvent systems. J Biomed Mater Res 59:563-72
Meese, Thomas M; Hu, Yunhua; Nowak, Richard W et al. (2002) Surface studies of coated polymer microspheres and protein release from tissue-engineered scaffolds. J Biomater Sci Polym Ed 13:141-51
Azari, K; Doll, B A; Sfeir, C et al. (2001) Therapeutic potential of bone morphogenetic proteins. Expert Opin Investig Drugs 10:1677-86
Hu, Y; Hollinger, J O; Marra, K G (2001) Controlled release from coated polymer microparticles embedded in tissue-engineered scaffolds. J Drug Target 9:431-8