The field of tissue engineering has developed due to the inadequate supply of organs and tissues for patients requiring organ/tissue replacement. An attractive alternative to organ and tissue transplantation that could immensely expand clinicians' ability to treat patients requiring new organs and tissues is the selective transplantation of the appropriate cell type(s). Transplanting cell populations on biodegradable polymer matrices in order to engineer a functional tissue mass from these transplanted cells is an intriguing strategy. However, the survival of these cells is dependent on diffusion of nutrients and waste products between the transplanted cells on the matrix and the vasculature existing in the surrounding host tissue. Currently, this vascular network is the limiting factor in allowing the engineering of large-scale masses of tissue capable of forming whole organs. The proposed research focuses on strategies to increase the vascular network within these polymer matrices in order to create significant amounts of bone tissue capable of replacing osseous defects.
The specific aims of this proposal are:
Aim 1 -To define strategies to engineer microvascular endothelial cells to produce growth factors/mediators that a) will induce a vigorous and sustained angiogenic response, and b) will induce bone development and growth from osteogenic precursors. We will initially look at the mediators Bcl-2, angiopoietin (two potent inducers of angiogenesis), and the osteogenic mediator BMP-2;
Aim 2 - To incorporate these different endothelial cell populations into biodegradable polymer matrices and to test their individual and combined abilities to form capillaries in vitro and in vivo;
Aim 3 - To determine the baseline bone formation when osteo-progenitor cells are transplanted on a biodegradable matrix;
Aim 4 -To determine if an appropriate combination of endothelial cells, osteo-progenitor cells, and matrix, as determined in Specific Aims 1-3, will result in a sustained and vigorous angiogenic response in vivo (SCID mouse model) capable of supporting bone development from osteo-progenitor cells.
| Kaigler, Darnell; Wang, Zhuo; Horger, Kim et al. (2006) VEGF scaffolds enhance angiogenesis and bone regeneration in irradiated osseous defects. J Bone Miner Res 21:735-44 |
| Kaigler, D; Krebsbach, P H; Wang, Z et al. (2006) Transplanted endothelial cells enhance orthotopic bone regeneration. J Dent Res 85:633-7 |
| Kaigler, Darnell; Krebsbach, Paul H; West, Erin R et al. (2005) Endothelial cell modulation of bone marrow stromal cell osteogenic potential. FASEB J 19:665-7 |
| Kaigler, Darnell; Krebsbach, Paul H; Polverini, Peter J et al. (2003) Role of vascular endothelial growth factor in bone marrow stromal cell modulation of endothelial cells. Tissue Eng 9:95-103 |
| Kaigler, D; Mooney, D (2001) Tissue engineering's impact on dentistry. J Dent Educ 65:456-62 |
