Cortical neural prostheses are a promising approach to alleviate symptoms for a wide range of neurodegenerative disorders, ranging from Alzheimer's and Parkinson's disease to paralyzing brain trauma injuries, such as stroke. A major impediment in these devices is the slow deterioration of signal quality under chronic conditions mainly due to (1) mechanical damage to the brain tissue, (2) biological rejection stemming from neuroinflammation processes, and (3) disconnection of neurons from the electrode at the neural interface. The overall objective of this research proposal is to develop a strategy for maintaining the neural-electrode interface connection and improve signal quality using a previously developed MEMS based moveable microelectrode array. Current approaches attempt to reduce inflammation and encourage neural connectivity by incorporating anti-inflammatory biochemicals in various polymer-matrices as coatings surrounding the microelectrodes. The primary focus has been to suppress inflammation via biochemical release. Here we propose to take a step further and attempt to prevent mechanical damage and minimize inflammation by tuning the mechanical properties of a hydrogel coating encapsulating a polysilicon moveable microelectrode. We will test the hypothesis that polysilicon microelectrodes encapsulated in a hydrogel coating with similar viscoelastic properties of brain tissue will cause less strain on the tissue, leading to less neuroinflammation and improved signal quality under chronic conditions. The ultimate goal is to develop a composite hydrogel that prevents mechanical damage and maintains a functional neural interface under chronic conditions. To achieve this goal, the specific aims are (1) to determine whether the crosslinking density and related stiffness of an encapsulating hydrogel will minimize gliosis and brain tissue damage and (2) to determine whether the combination of electrode movement and incorporation of biochemical's such as NGF within hydrogel coatings will promote better neural connectivity and improved signal quality. The effect of hydrogel coated microelectrodes on brain tissue will be characterized with a rodent model under chronic conditions using histological, electrical, and mechanical methods to test for reduction of neuroinflammation. Using force displacement data for various coated microelectrodes, we will generate a finite element based hyperelastic model of brain tissue under chronic conditions. Additionally, we will characterize the synergistic use of electrode movement and nerve growth factor (NGF) incorporated in hydrogels under chronic conditions using electrophysiological and histological characterization. Successful outcomes of this proposal will entail development of novel strategies for long-term implantation of neural prosthetic devices and better understanding of the impact of microelectrodes on the brain material properties under chronic conditions.
The proposed study to develop novel bioactive coatings will help to incorporate life-saving neural implants over the long term. Successful outcomes of this proposal will lead to novel approaches to develop methods to incorporate neural prosthetics and other biomedical devices with reduced biological rejection and increased device functionality. Chronic implantation of neural prosthetics will help in the treatment of debilitating diseases like Alzheimer's disease, Parkinson's disease, and stroke.
|Sridharan, Arati; Rajan, Subramaniam D; Muthuswamy, Jit (2013) Long-term changes in the material properties of brain tissue at the implant-tissue interface. J Neural Eng 10:066001|