Investigation of Material and Therapeutic Strategies to Reduce the Inflammatory Response to Intracortical Implants

Links

URL: http://rave.ohiolink.edu/etdc/view?acc_num=case1431086131

Abstract

Intracortical microelectrodes have provided researchers with a tool to understand the neural system and restore motor control in patients with tetraplegia. However, recording instability and variability throughout implantation lifetime have limited the potential of microelectrodes. The biological response to implanted microelectrodes is a major contributor to device failure. The overall goal of this work was to explore material and therapeutic strategies to reduce the inflammatory response to intracortical implants. In this dissertation, we investigated the effect of material compliance on the neuroinflammatory response. Use of soft modulus, compliant materials that more closely match the brain modulus significantly reduced the neuroinflammatory response compared to traditional, stiff materials. Additionally, we report on acute force measurements of tissue strain from implanted microelectrodes. Our results indicated that compliant implants reduced the dynamic stress relaxation rate of the brain tissue and micromotion-induced tissue stresses compared to stiff implants. To further modulate the neuroinflammatory response, we also report on antioxidant-releasing compliant implants. The neuroinflammatory response is complex and adaptive, and we hypothesized that coupling of compliant materials and antioxidant therapy may further improve microelectrode integration. Antioxidant release from compliant materials demonstrated the short-term benefits of antioxidant treatment and long-term reduction in neuroinflammation with compliant materials. Furthermore, we developed a method to chemically-conjugate an antioxidant mimetic on the microelectrode surface to create a more sustained antioxidative effect. The results of this work provide support for the use of compliant materials and antioxidant therapies to improve microelectrode integration. Further, the work here additionally substantiates that combining multiple strategies may better enhance modulation of the neuroinflammatory response and improve reliability of intracortical microelectrodes.

Cited Works (3)

Year	Entry
1992	Oliver WC, Pharr GM. An improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experiments. J Mater Res. 1992;7(6):1564-1583.
2005	LaPlaca MC, Cullen DK, McLoughlin JJ, Cargill RS II. High rate shear strain of three-dimensional neural cell cultures: a new in vitro traumatic brain injury model. J Biomech. May 2005;38(5):1093-1105.
2003	Gefen A, Gefen N, Zhu Q, Raghupathi R, Margulies SS. Age-dependent changes in material properties of the brain and braincase of the rat. J Neurotrauma. November 2003;20(11):1163-1177.