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theses

Cortical implants are an important component of a variety of novel therapeutic technologies, such as brain-computer interfaces for prosthetic control and sensory restoration devices. However, the widespread use of these devices is limited by the brain’s endogenous foreign body response (FBR) to cortical implants, which involves inflammation and scar tissue formation. FBR is exacerbated by three major factors: reactive chemical pathways such as cytokine gradients, mechanical mismatch between the stiff implant and soft brain tissue, and micromotion at the implant-tissue interface caused by pulsation of brain tissue due to respiration and circulation. This project focused on developing and analyzing hydrogel coatings that attenuate these factors. We worked with three different hydrogel systems—a polyelectrolyte gel, a guest-host gel, and a self-assembling peptide gel—and used mechanical and bio-functional strategies to optimize them for performance as implant coatings. The coatings are designed to closely match the mechanical properties of brain tissue to address mechanical mismatch. They contain physical, non-covalent bonds within their polymer networks that can dissociate and reform to absorb the kinetic energy generated by micromotion, preventing it from perturbing brain tissue. The self-assembling peptide gel contains a cytokine sequestration motif that aims to reduce the activation of inflammatory recruitment agents, addressing the chemical causes of FBR. As part of this project, we developed a custom open-source device to simulate micromotion between an implant and surrounding tissue. We use the device, as well as other methods such as cytotoxicity assays and rheological analysis, to characterize the hydrogels and compare the effectiveness of various modifications. We developed versions of the hydrogels adapted for use as implant coatings that outperformed covalent hydrogel PEGDA at reducing micromotion at the implant interface. Our work with the self-assembling peptide gel focused on molecular dynamics simulation of the cytokine sequestration motif’s assembly with the cytokine CCL2 in order to develop an improved peptide motif that maximized CCL2 affinity. We demonstrated that the new motif outperforms the original motif at sequestering CCL2. Overall, this work represents advancement in development of FBR-reducing implant coatings, as well as in the techniques used to evaluate their efficacy.

http://dissertations.umi.com/gsnb.rutgers:12421

Ph.D.

Includes bibliographical references

doi:10.7282/t3-6cnz-3s32

The author owns the copyright to this work.