Vicki Colvin1
Brown University1
Medical devices implanted in the human body are increasingly common in the management and treatment of disease. An important and growing subset of these devices termed here ‘active’ implants, require electrical contact with tissues. For these devices the foreign body response to an electrode can preclude chronic function and limit many applications. The local delivery of an antioxidant able to protect tissue for months or even years is one possible solution. Nanoparticle ceria is a perpetual antioxidant due to its large cerium(III) content and the possibility of recovering cerium(III) from cerium(IV) after use.[1] For this work its antioxidant capacity was augmented by the use of molecular tethers that stabilized the reactive Ce(III) state. The efficacy of these materials was evaluated in a three-dimensional in vitro model by seeding primary cortical cells around microwires to reveal independent innate neuroinflammation. We demonstrated the use of ceria nanoparticles for reducing oxidative stress, increasing neuronal density, and reducing functional connectivity in wire implanted samples. These results indicate that antioxidant ceria nanoparticles may be efficacious drug treatment for protecting neural function at the device-tissue interface. We optimized ceria nanoparticles for small diameter, biocompatibility, and colloidal stability using reactive polymer coatings. To evaluate their utility in combating inflammation, we developed a 3D in vitro model of the device-tissue interface. This system can disentangle the different contributions of the innate immune system to neuroinflammatory device responses. Ceria nanoparticles reduced the oxidative stress, increased neuronal density, and reduced functional connectivity in wire-implanted samples [2]. The development and characterization of a novel 3D in vitro model of the device-tissue interface revealed a significant innate immune response to neural implants. This study has broad implications for the role of the innate immune system and potential treatment strategies for the chronic foreign body response to neural implants. The mitigation of oxidative stress, neuronal density, and functional connectivity with antioxidant ceria nanoparticles offers significant supporting evidence to indicate that many symptoms of the tissue reaction are related to redox dysregulation. Successful treatment of the device-tissue interface with long-acting antioxidant ceria nanoparticles shows potential for a local long-term antioxidant treatment strategy for clinical applications that need the long-term use of implanted neural devices.<br/><b>References</b>:[1] <i>ACS Nano</i> 2013, 7, 11, 9693–9703 [2] J. Neural Eng. (2022) v. 19 iss. 3