Graduation Semester and Year

2006

Language

English

Document Type

Thesis

Degree Name

Master of Science in Biomedical Engineering

Department

Bioengineering

First Advisor

Liping Tang

Abstract

The most troublesome biological response to the implantation of bloodcontacting biomaterials is inflammation, which thereby-sets in motion a cascade of adverse host responses. If devices for therapy and drug delivery could be developed that prevent such responses from occurring altogether, a new generation of "stealth" biomaterials would be born. Such was the motivation of this project, which sought to investigate using mouse subcutaneous implantation model, the implant mediated host tissue responses to surfaces differing in their functionalities. During the course of a previous study in our laboratory, we accidentally discovered the presence of stem cells and their accumulation at the capsule around microparticle implants.31 In our present study, as the recruitment of stem cell coincided with that of the inflammatory cells, we believe that stem cells get actively recruited by the inflammatory response induced by the biomaterial implantation. As the first stage of our investigation, to test this hypothesis, we evaluated the host tissue responses to polypropylene particles with surfaces, modified using radio frequency glow discharge plasma polymerization to have high concentrations of -OH, -NH2, -CF3 and -COOH groups. The extent of inflammatory responses mediated by the biomaterial implantation and corresponding stem cell recruitment were assessed following implantation, using immunohistological analyses. Our results indicate that surface functionalities significantly affect both capsule formed around the implant and the inflammatory cells, with leukocyte marker CD11b, recruited to the implant. In addition, we have also uncovered many cells that stain positive with stem cell markers SCF, Nanog and SH2B. Our results reveal that chemical characteristics of material surfaces play important roles in biomaterial mediated tissue responses. Surfaces with -NH2 and -OH groups showed the highest number of inflammatory cells at the capsule along with the thickest capsule measured in microns. Interestingly, we observed that all five surfaces provoked different extents of recruitment of these stem cells at the capsule. The -COOH group showed the maximum number of positive cells for all three stem cell markers. Unexpectedly, an inverse relation between recruited inflammatory and stem cells was found for most surfaces , suggesting that stem cells are different and distinct from the inflammatory cells, though both were influenced by the implant mediated foreign body response. The underlying mechanism is yet to be determined. Overall, our results indicate that the surface functional groups influence not only the inflammatory responses but also the biomaterial mediated stem cell recruitment, inside the host.

Disciplines

Biomedical Engineering and Bioengineering | Engineering

Comments

Degree granted by The University of Texas at Arlington

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