An understanding of the interactions between orthopaedic and dental implant
surfaces with the surrounding host tissue is critical in the design of next generation
implants to improve osseointegration and clinical success rates. Critical to the process
of osseointegration is the rapid establishment of a patent neovasculature in the peri-implant
space to allow for the delivery of oxygen, nutrients, and progenitor cells. The
central aim of this thesis is to understand how biomaterials regulate cellular and host
tissue response to elicit a pro-angiogenic microenvironment at the implant/tissue
interface. To address this question, the studies performed in this thesis aim to 1)
determine whether biomaterial surface properties can modulate the production and
secretion of pro-angiogenic growth factors by cells, 2) determine the role of integrin and
VEGF-A signaling in the angiogenic response of cells to implant surface features, and 3)
to determine whether neovascularization in response to an implanted biomaterial can be
modulated in vivo. The results demonstrate that biomaterial surface microtopography
and surface energy can increase the production of pro-angiogenic growth factors by
osteoblasts and that these growth factors stimulate the differentiation of endothelial cells
in a paracrine manner and the results suggest that signaling through specific integrin
receptors affects the production of angiogenic growth factors by osteoblast-like cells.
Further, using a novel in vivo model, the results demonstrate that a combination of a
rough surface microtopography and high surface energy can improve bone-to-implant
contact and neovascularization. The results of these studies also suggest that VEGF-A
produced by osteoblast-like cells has both an autocrine and paracrine effect. VEGF-A
silenced cells exhibited reduced production of both pro-angiogenic and osteogenic
growth factors in response to surface microtopgraphy and surface energy, and
conditioned media from VEGF-A silenced osteoblast-like cell cultures failed to stimulate
endothelial cell differentiation in an in vitro model. Finally, the results show that by
combining angiogenic and osteogenic biomaterials, new bone formation and
neovascularization can be enhanced. Taken together, this research helps to provide a
better understanding of the role of material properties in cell and host tissue response
and will aid in the improvement of the design of new implants.
| Identifer | oai:union.ndltd.org:GATECH/oai:smartech.gatech.edu:1853/41178 |
| Date | 08 July 2011 |
| Creators | Raines, Andrew Lawrence |
| Publisher | Georgia Institute of Technology |
| Source Sets | Georgia Tech Electronic Thesis and Dissertation Archive |
| Detected Language | English |
| Type | Dissertation |
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