The ultimate goal of this research project is to develop osteoinductive osteoblast/polymer constructs for bone regeneration and repair. We will investigate the effects of flow and fluid shear, as well as scaffold pore architecture and surface composition on the proliferation and osteogenic differentiation of marrow stromal cells seeded in three-dimensional biodegradable polymer scaffolds and cultured in vitro in a flow perfusion bioreactor developed in our laboratory. We will determine the effects of these parameters on the secretion and deposition of osteoinductive and angiogenic growth factors, such as bone morphogenetic protein-2 and vascular endothelial growth factor, the secretion of bone matrix proteins, such as osteocalcin, and the deposition of mineralized extracellular matrix. We will also investigate the effects of fluid shear and in vitro culture period on mineralized tissue formation after implantation of the cell/polymer constructs in the mesentery of rats and will elucidate the contributions of the mineralized extracellular matrix generated in vitro and the differentiated cells existing in the cell/polymer constructs on the construct osteoinductivity in vivo. Lastly, we will evaluate the ability of optimized cell/polymer constructs created in vitro under flow perfusion culture and loaded with deposited osteoinductive extracellular matrix and secreted angiogenic factors to form new bone in an orthotopic site and restore osseous continuity using a critical size cranial defect model in rats. New bone formation will be assessed radiographically and histomorphometrically as a function of time. Light and fluorescence microscopy will allow quantitative and qualitative analyses of the extent, character, and dynamics of new bone formation. The mechanical properties of the grafted bones will be measured to verify restoration of the integrity of the reconstituted region. This project will provide clinically valuable information regarding new tissue-inducing orthopaedic biomaterials which are becoming particularly important because of the renewed concern for the safety of non-degradable implants and the potential for disease transmission with allografts.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR042639-09
Application #
6909099
Study Section
Special Emphasis Panel (ZRG1-OBM-2 (01))
Program Officer
Panagis, James S
Project Start
1996-04-15
Project End
2007-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
9
Fiscal Year
2005
Total Cost
$209,638
Indirect Cost
Name
Rice University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
050299031
City
Houston
State
TX
Country
United States
Zip Code
77005
Spicer, Patrick P; Kretlow, James D; Young, Simon et al. (2012) Evaluation of bone regeneration using the rat critical size calvarial defect. Nat Protoc 7:1918-29
Sitharaman, Balaji; Van Der Zande, Meike; Ananta, Jeyarama S et al. (2010) Magnetic resonance imaging studies on gadonanotube-reinforced biodegradable polymer nanocomposites. J Biomed Mater Res A 93:1454-62
Shi, Xinfeng; Sitharaman, Balaji; Pham, Quynh P et al. (2008) In vitro cytotoxicity of single-walled carbon nanotube/biodegradable polymer nanocomposites. J Biomed Mater Res A 86:813-23
Sitharaman, Balaji; Zakharian, Tatiana Y; Saraf, Anita et al. (2008) Water-soluble fullerene (C60) derivatives as nonviral gene-delivery vectors. Mol Pharm 5:567-78
Pham, Quynh P; Kasper, F Kurtis; Scott Baggett, L et al. (2008) The influence of an in vitro generated bone-like extracellular matrix on osteoblastic gene expression of marrow stromal cells. Biomaterials 29:2729-39
Mistry, A S; Mikos, A G; Jansen, J A (2007) Degradation and biocompatibility of a poly(propylene fumarate)-based/alumoxane nanocomposite for bone tissue engineering. J Biomed Mater Res A 83:940-53
Christenson, Elizabeth M; Anseth, Kristi S; van den Beucken, Jeroen J J P et al. (2007) Nanobiomaterial applications in orthopedics. J Orthop Res 25:11-22
Sitharaman, Balaji; Shi, Xinfeng; Tran, Lesa A et al. (2007) Injectable in situ cross-linkable nanocomposites of biodegradable polymers and carbon nanostructures for bone tissue engineering. J Biomater Sci Polym Ed 18:655-71
Shi, Xinfeng; Sitharaman, Balaji; Pham, Quynh P et al. (2007) Fabrication of porous ultra-short single-walled carbon nanotube nanocomposite scaffolds for bone tissue engineering. Biomaterials 28:4078-90
Kretlow, James D; Mikos, Antonios G (2007) Review: mineralization of synthetic polymer scaffolds for bone tissue engineering. Tissue Eng 13:927-38

Showing the most recent 10 out of 37 publications