Biomaterials are used in many different areas. Often, after implantation, severe host reactions occur which cause the malfunction or failure of the device. In our study, we wanted to investigate the mechanism of biomaterial-induced fibrosis. We focused on three areas: i) the relationship between inflammation and fibrosis after implantation, ii) the role that the SMAD3 gene plays, and iii) how MRL mice react to biomaterials. After implantation, acute inflammation occurs immediately. In pathological fibrosis, it has traditionally been believed that the inflammation is linked to the downstream fibrosis, though this theory has been challenged recently. In our project, we did not observe a direct relationship between intentionally induced inflammation and biomaterial-induced fibrosis. We did observe the dependency of the host reaction on the type of implanted biomaterial. The SMAD3 gene is tightly linked to the pro-fibrotic cytokine TGF-(beta). The SMAD3 protein mediates the TGF-(beta) pathway intracellularly. It was found in pulmonary fibrosis, SMAD3 knockout (KO) mice had lower production of collagen. In our project, we did not observe a difference in cellular behaviour on the surface of the implanted biomaterial between wild-type (WT) and SMAD3 KO mice. We did observe a difference in the production of TGF-(beta)1. This could be a clue that biomaterial-induced fibrosis has more than one mechanism/pathway that is not dependent on TGF-(beta). In our last project, we studied MRL mice that showed potential in scarless wound healing. We observed a higher production of MMP-2, MMP-9 and TGF-(beta)1. Histologically, however, we did not see a difference in cellular behaviour between MRL and C57BL/6 mice. Our results open up the possibilities of different mechanisms and pathways in biomaterial-induced fibrosis. Future studies of cytokines and specific cells could help us further understand the process of encapsulation of the implanted biomaterials. / Thesis / Master of Applied Science (MASc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/23288 |
| Date | 09 1900 |
| Creators | Chang, Albert |
| Contributors | Jones, K., Chemical Engineering |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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