(verbatim) Bone loss due to trauma or disease is traditionally treated using autografts or allografts. However, these materials have certain drawbacks which limit their use. Thus, the objective of this project is to use a tissue engineering approach to develop new materials as practical alternatives to current bone repair materials. The new materials will be based on 3-dimensional, porous composites formed from degradable phosphazene polymers and synthetic hydroxyapatite, with the final biomaterial having strength, impact-resistance, adhesion to existing hard tissue and the ability to bioerode as regeneration of living tissue occurs via colonization by osteoblasts. A major feature of the new materials will be their ability to be shaped at the time of surgery and to harden at body temperature without damage to surrounding tissue. This will be achieved through the use of biocompatible polyphosphazenes and hydroxyapatite precursors specifically designed to be moldable at room temperature and subject to spontaneous cure at body temperature. In this project, several composites will be designed, synthesized, fabricated and tested in vitro. From these studies, the best composites will then be evaluated in vivo in a rabbit model for bone repair. The program has 3 specific aims: (1) The design, synthesis and characterization of biodegradable polymers which can interact in an appropriate manner with hydroxyapatite precursors to permit the formation of composites with properties mimicking cancellous bone; (2) The preparation and physico-chemical evaluation of composites in vitro as a means for predicting composite features likely to be optimal for indications requiring the regeneration or replacement of bone in vivo; and (3) In vitro and in vivo biological and biomechanical evaluation of the composites. This project is a collaboration between 3 research groups with expertise that encompasses and overlaps each aim. It is anticipated that at the completion of this project, a viable alternative to existing bone repair materials may be established.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR046560-05
Application #
6784522
Study Section
Special Emphasis Panel (ZRG1-SSS-M (01))
Program Officer
Panagis, James S
Project Start
2001-04-01
Project End
2006-07-31
Budget Start
2004-08-01
Budget End
2006-07-31
Support Year
5
Fiscal Year
2004
Total Cost
$701,033
Indirect Cost
Name
University of Virginia
Department
Orthopedics
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
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Laurencin, Cato T; Khan, Yusuf; Kofron, Michele et al. (2006) The ABJS Nicolas Andry Award: Tissue engineering of bone and ligament: a 15-year perspective. Clin Orthop Relat Res 447:221-36
Greish, Y E; Bender, J D; Lakshmi, S et al. (2006) Formation of hydroxyapatite-polyphosphazene polymer composites at physiologic temperature. J Biomed Mater Res A 77:416-25
Nair, Lakshmi S; Lee, Duron A; Bender, Jared D et al. (2006) Synthesis, characterization, and osteocompatibility evaluation of novel alanine-based polyphosphazenes. J Biomed Mater Res A 76:206-13
Greish, Y E; Bender, J D; Lakshmi, S et al. (2005) Low temperature formation of hydroxyapatite-poly(alkyl oxybenzoate)phosphazene composites for biomedical applications. Biomaterials 26:1-9
Greish, Y E; Bender, J D; Lakshmi, S et al. (2005) Composite formation from hydroxyapatite with sodium and potassium salts of polyphosphazene. J Mater Sci Mater Med 16:613-20

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