Integration of foreign materials into the CNS or PNS has proved to be very difficult. Long term exposure of materials to the environment either ends in device encapsulation by glial cells or targeted neurons in the area either die or pull their synaptic activities far from the device. We are investigating three important areas that are believed to be the cause for these problems.
1. Biocompatibility of the material: Biocompatibility has many definitions, but basically investigates if the body sees the material as foreign substance and starts the immune response cascade as well as does the material retain its ability to do what it was designed to do within the environment of the body.
2. The micromotion of the brain: The brain is suspended in cerebral-spinal fluid and moves constantly in relation to the skull. The elasticity/ stiffness of the material in relation to the brain, one of the softest materials in the body, is important in the long term integration of the device. Micromotion coupled to the device elasticity may cause secondary damage and initiate a permanent chronic immune response.
3. Shape of the device: We are looking at the effects of various architectures as they pertain to initial invasiveness and long term reaction to the shape.
Dr. Frewin has investigated silicon carbide (SiC) and nanocrystalline diamond (NCD) materials in vitro and in vivo using methodologies developed in accordance with ISO 10993-1 and ISO 10993-5. Cells on biocompatible surfaces will interact with the substrate by increasing their attached area and will have greater viability than cells interacting with unsuitable or toxic surfaces. Thus, cell morphology and viability can be used as measures of surface biocompatibility. We have developed a novel approach to measure substrate permissiveness by examining lamellipodia, the part of the neuron involved in axon and dendrite generation as well as cell mobility via atomic force microscopy.
Figure (Below) 3C-SiC Biocompatibility
3C-SiC shows good biocompatibility with both neural cells (the PC12 and primary cortical cells) as well as glial cells (H4 cells) in vitro. A. The MTT tests are comparable with polystyrene, and B. the cells show expansion of lamellipodia and filopodia by AFM as well as microtubule structures. C is SEM image of a typical primary mouse neuron cultured on 3C-SiC. D In vivo, 3C-SiC shows little to no CD45 glial reactivity after 35 days, with the exception of the large proliferation within the diamond cut trench through the 3C-SiC surface layer which exposed the Si substrate below (indicated by white*). The surface of Si shows the same reaction seen in the Si trenches on the 3C-SiC surface.
The following links will show the results of our current exploration into SiC and NCD devices as well as the electrophysiology we have performed with SiC and NCD.
This work was funded by:
A grant from the USF Neuroscience Collaborative (NSC),
National Institutes of Health Ruth L. Kirschstein National Research Service Award (NRSA) to C. Frewin, and
A grant from the
Florida Center of Excellence for Biomolecular Identification and Targeted Therapeutics (Now CDDI). |
