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LYMPHOCYTE AND MACROPHAGE INTERACTIONS IN THE RESPONSE TO BIOMATERIAL SURFACES

Chang, David T.
http://rave.ohiolink.edu/etdc/view?acc_num=case1207073535

Abstract Details

2008, Doctor of Philosophy, Case Western Reserve University, Biomedical Engineering.
Synthetic polymers provide a wide array of physical properties and chemical compositions that can be exploited as components in prosthetics, devices, and tissue-engineered constructs. This requires elucidating the biological response to biomaterials and the relationship between surface characteristics and cellular behavior. Lymphocytes transiently appear at implant sites and have been observed clinically to be reactive. However, the role of lymphocytes in the tissue response and the mechanisms involved are still unclear. This research aimed to gain insight into the interactions between lymphocytes and macrophages at biomaterial surfaces and explore the relationship between surface properties and lymphocyte/macrophage interactions. The studies addressed the hypothesis that biomaterial surface chemistries modulate the direct and indirect lymphocyte interactions with macrophages and foreign body giant cells. PET-based photograft copolymerized surfaces with hydrophobic, hydrophilic/neutral, hydrophilic/anionic, and hydrophilic/cationic characteristics were utilized as model surfaces. Quantification of select inflammatory mediators showed that hydrophilic/neutral and hydrophilic/anionic surfaces promoted pro-inflammatory responses and a reduced potential for ECM degradation relative to other surfaces. Proteomic cytokine arrays provided a useful tool for assessing the role of soluble mediators in the response to biomaterials and identified potential fusion factors. We subsequently showed the capability of lymphocytes, through direct and indirect mechanisms, to enhance macrophage activation and production of pro-inflammatory mediators. Hydrophilic/neutral and hydrophilic/anionic surfaces were shown to be highly but distinctly activating. These surfaces also promoted distinct lymphocyte subset adhesion to macrophages and FBGCs compared to hydrophobic PET suggesting induction of differential macrophage and FBGC phenotypes on varying biomaterial surfaces. IFN-γ production in direct and indirect co-cultures rather than individual cultures suggested nonspecific mechanisms of lymphocyte activation. Direct cell-cell interactions enhanced IFN-γ production more so on the hydrophilic/anionic surfaces than on any other surface, indicating this surface as highly lymphocyte activating. These findings provide insight into lymphocyte and macrophage interactions in response to biomaterial surfaces along with evidence consistent with the hypothesis that distinct surface chemistries modulate lymphocyte and macrophage interactions. Finally, we present a mechanistic model which provides a tool for further analysis of lymphocyte and macrophage interactions in response to biomaterial surfaces and a step toward quantitative predictability of biomaterial-dependent processes.
Roger E. Marchant, PhD (Committee Chair)
James M. Anderson, MD, PhD (Advisor)
Gerald M. Saidel, PhD (Committee Member)
Edward Greenfield, PhD (Committee Member)
Horst von Recum, PhD (Committee Member)
290 p.
Biomedical Research; Engineering
biomaterials; foreign body reaction; foreign body giant cells; macrophages; lymphocytes; activation; cytokines

Recommended Citations

Citations

  • Chang, D. T. (2008). LYMPHOCYTE AND MACROPHAGE INTERACTIONS IN THE RESPONSE TO BIOMATERIAL SURFACES [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1207073535

    APA Style (7th edition)

  • Chang, David. LYMPHOCYTE AND MACROPHAGE INTERACTIONS IN THE RESPONSE TO BIOMATERIAL SURFACES. 2008. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1207073535.

    MLA Style (8th edition)

  • Chang, David. "LYMPHOCYTE AND MACROPHAGE INTERACTIONS IN THE RESPONSE TO BIOMATERIAL SURFACES." Doctoral dissertation, Case Western Reserve University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=case1207073535

    Chicago Manual of Style (17th edition)

case1207073535
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© 2008, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.