Treatment to correct osseous or orofacial deficiencies is a formidable, persistent challenge. In the spirit of the Program Announcement (PA), this proposal focuses on development of a """"""""biomaterial to treat craniofacial injuries and disorders"""""""". Surgical management of these conditions would be simplified if a reliable, convenient, off-the-shelf biomaterial were available in the operating room. A biomaterial that would replace autografts and bank bone would be a welcomed alternative. Consequently, within the province of the NIH's PA on Oral Wound Healing and Tissue Regeneration we propose an alternative: recombinant human bone morphogenetic protein-2 (rhBMP-2) and a synthetic carrier. RhBMP-2 has been scrutinized in a legion of in vitro and animal studies, from rats to non-human primates. It is effective and efficacious. However;, development of a carrier for rhBMP-2 is pivotal to its successful clinical applications. Several key characteristics of an rhBMP- 2 carrier include biocompatibility, porous architecture for osteoconduction, appropriate pharmacokinetics for rhBMP-2 release, controlled mass loss and biodegradation coordinated with new bone formation. The objective of this study is to develop a biomaterial for the treatment of bone defects. Consequently, the purposes have been structured 1) to design a porous L-polyactide (PLLA) carrier for rhBMP-2 delivery, and 2) to test the capability of different doses of rhBMP-2/PLLA to regenerate osseous contour to standardized, reproducible orofacial defects in dogs and nonhuman primates (NHPs). The hypotheses are that rhBMP-2/PLLA within the defects will 1) regenerate bone in a dose- and time-dependent fashion, and 2) at least one dose of rhBMP-2/PLLA will be as effective as the autograft. To test our hypotheses, PLLA will be designed to deploy rhBMP-2. Orofacial defects in dogs and NHPs will be implanted with an autograft, one of three different doses of rhBMP-2/PLLA, or left untreated. Recipient sites will be recovered at specified times and bone formation will be measured by radiomorphometry and histomorphometry. Confirmation of the hypotheses will be accomplished by analyzing quantitative morphologic data for new bone formation at the defects in response to the different treatments.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE011416-02
Application #
2430128
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1996-06-01
Project End
2000-05-31
Budget Start
1997-06-01
Budget End
1998-05-31
Support Year
2
Fiscal Year
1997
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
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
Winn, S R; Schmitt, J M; Buck, D et al. (1999) Tissue-engineered bone biomimetic to regenerate calvarial critical-sized defects in athymic rats. J Biomed Mater Res 45:414-21
Winn, S R; Uludag, H; Hollinger, J O (1999) Carrier systems for bone morphogenetic proteins. Clin Orthop Relat Res :S95-106
Schmitt, J M; Hwang, K; Winn, S R et al. (1999) Bone morphogenetic proteins: an update on basic biology and clinical relevance. J Orthop Res 17:269-78
Hollinger, J O; Schmitt, J M; Buck, D C et al. (1998) Recombinant human bone morphogenetic protein-2 and collagen for bone regeneration. J Biomed Mater Res 43:356-64