Immunomodulatory Effects of Engineered Biomimetic Materials
- Author(s): Chen, Esther Yu-Tin
- Advisor(s): Liu, Wendy F
- et al.
Biocompatibility is an essential parameter to evaluate when designing the biomaterial in order to induce an appropriate host response in its specific application. Generally, biocompatibility refers to the lack of foreign body response to an implanted or injected material. The foreign body response involves activation of various immune cells and leads to severe inflammation, and eventually device failure. Modulation of the foreign body response to biomaterials therefore is a key to translating medical devices into the clinic. There have been various chemical and physical approaches to overcome the foreign body response. However, these methods do not provide any specific biological signal to immune cells, such as macrophages, who have diverse functionalities at different stages of inflammation. Therefore, a biological approach to mitigate the foreign body response to the biomaterials is essential.
This Ph.D. dissertation utilizes a biomolecular design of biomaterials to mimic the host tissue by displaying an immunomodulatory molecule on the surface, providing a specific inhibitory signaling to the immune cells. The immunomodulatory molecule that we exploit is CD200, which has been shown to interact with its inhibitory receptor, CD200R on myeloid cells, suppressing the activation of myeloid cells. In this study, we focus on a biomaterial that has been widely used in FDA-approved devices, poly (lactic-co-glycolic) acid (PLGA). Even though PLGA is relatively biocompatible, as a foreign material, it initiates inflammation. This dissertation focuses on the fabrication of CD200-coated PLGA materials and their immunomodulatory effects on macrophages. We synthesize CD200-coated PLGA in different geometries and study macrophage behaviors including cytokine secretion and phagocytosis.
This Ph.D. study suggests that immunomodulatory coating of CD200 on PLGA mitigates macrophage activation and the effect of CD200 is geometry-dependent. Specifically, CD200-coated PLGA films and microparticles exhibit anti-inflammatory property, while the effect of CD200-coated PLGA nanoparticles on macrophage cytokine secretion is minimum. Additionally, macrophages phagocytose more CD200-coated microparticles, whereas they uptake less CD200-coated nanoparticles, when compared to the unmodified particles. This dissertation suggests that CD200-coated microparticles and films can be used as implantable biomaterials to silence inflammation, while CD200-coated nanoparticles propose an improved drug delivery system.