Tissue engineering has developed into a truly interdisciplinary field offering promises to revitalize or replace damaged or lost human tissue/organs. Tissue engineering has been defined as the application of biological, chemical and engineering principles toward the repair, restoration or regeneration of living tissue using biomaterials, cells and factors alone or in combination. The major components of tissue engineered products are the three dimensional scaffold with/without factors and the appropriate cells. Bone tissue engineering requires scaffolds with optimal properties that include strength, toughness, porosity, controlled rate of degradation, non-toxic degradation products, minimal inflammatory response, moldability, osteoconductivity and osteoinductivity. In the proposed work, we will focus on the development of novel three-dimensional (3-D) composite scaffolds with optimal properties for bone tissue engineering. Composite matrices will be made from novel polymers based on polyphosphazenes and hydroxyapatite (HA). We hypothesize that these 3-D composites, which combine the controlled degradation rate, biocompatibility and osteoconductivity of polyphosphazenes with the bioactivity of HA, can eventually mimic the biological and mechanical properties of bone, which itself is a composite. The overall goal is to design and develop three-dimensional scaffolds with controlled physico-chemical and biological properties that will be a practical alternative to current bone repair materials. This goal will be achieved via the following specific aims:
Specific Aim 1 : The design, synthesis, and characterization of novel biodegradable polyphosphazenes with appropriate thermal, biological and mechanical properties that can be processed with HA to form 3-dimensional matrices.
Specific Aim 2 : Development of novel 3-dimensional polyphosphazene-HA based composite matrices and evaluation of the biological and mechanical properties of the composites using in vitro techniques.
Specific Aim 3 : Evaluation of the biological performance of novel 3-D composite matrices using in vivo techniques.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR052536-01A2
Application #
7033124
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Panagis, James S
Project Start
2005-09-19
Project End
2010-07-31
Budget Start
2005-09-19
Budget End
2006-07-31
Support Year
1
Fiscal Year
2005
Total Cost
$297,768
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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Lo, Kevin W-H; Ashe, Keshia M; Kan, Ho Man et al. (2011) Activation of cyclic amp/protein kinase: a signaling pathway enhances osteoblast cell adhesion on biomaterials for regenerative engineering. J Orthop Res 29:602-8
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Cushnie, Emily K; Khan, Yusuf M; Laurencin, Cato T (2010) Tissue-engineered matrices as functional delivery systems: adsorption and release of bioactive proteins from degradable composite scaffolds. J Biomed Mater Res A 94:568-75
Deng, Meng; Nair, Lakshmi S; Nukavarapu, Syam P et al. (2010) Dipeptide-based polyphosphazene and polyester blends for bone tissue engineering. Biomaterials 31:4898-908

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