As the biomedical engineering field pushes forward in designing new implantable devices to improve the quality of life for many around the world, scientists and engineers are constantly confronted with the dilemma of choosing the correct biomaterials that will fulfill the requirements of the device and do not cause harm to the tissues surrounding the implant. This dilemma can be further complicated if the “bio-safe” material does not conform to the requirements of the device itself. The Biomimetic Microelectronic System-Engineering Research Center (BMES-ERC) at the University of Southern California (http://bmes-erc.usc.edu) is working on the development of neuromuscular, retinal, and cortical prostheses. As part of the BMES-ERC, the research in our group focuses on the retinal and cortical prostheses, with the goal of providing seamless biotic-abiotic interface between the device and its surrounding tissue.

Retinal Prosthesis

The epiretinal prosthesis targets blind patients due to illness such as Age Macular Degeneration (AMD) and Rentinitis Pigmentosa (RP). Loss of sight in AMD patients is due to degeneration or breakdown of macula, the retina part that forms the “center” of the image.  Some known treatments to minimize progression include laser treatment to seal off blood vessels that grow beneath the retina, repair of the macula’s weak spots or by removing worn-out tissue and allowing new tissue growth, but there is no known cure. There are approximately 70,000 new patients of AMD each year in United States. RP is a collective generic name for genetic defects that resulted in photoreceptor lost. Over 100 genetic defects have been linked to RP, and the overall incidence of RP is 1 every 4000 live births. Unfortunately, there is no known treatment for RP patients.
In both of these cases, the nerve optics of the retina is still functioning. The epiretinal prosthesis is aimed to “by-pass” the damage region of the retina while still utilizing the presence nerve optics by supplying input signal directly onto the nerve optic cells.
An ideal support material for the epiretinal implant is a thin polymer film that 1) allows metal patterning on the surface for formation of the multi-electrode array (MEA) pads, 2) has flexibility to conform to the retina curvature, 3) can act as an electrical insulator, 4) has good water barrier property, 5) provides good adhesion toward the metal pads, and 6) allows tissue attachment for device anchorage. Current method for anchoraging the epiretinal implant utilizes medical staples that mechanically hold the device in close proximity to the retina.
Poly-p-xylylene (also referred to as parylene) satisfies both the flexibility and the water barrier requirements for the MEA substrates. Parylene has previously been utilized in the coating of medical devices to provide inert, conformal coating and is approved for long-term implantation by the FDA. Parylene’s characteristics provide long-term stability and lubrication properties when used for the coating of a limb prosthetic but become an obstacle for application in the epiretinal prosthesis due to difficulties in forming a stable adhesion of the implant at a specific location.
We are developing surface modification methods for parylene and improving the adhesion of metals onto the parylene. We have achieved both temperature-dependent and temperature-independent adhesion of retinal tissues onto thin films of parylene in in vitro studies. Long-term in vivo studies will be carried out in conjunction with colleagues at the Doheny Eye Institute (http://www.doheny.org), here at USC.

Cortical Prosthesis

The cortical prosthesis under development by BMES-ERC focuses on developing a device that can replace the activities of the hippocampus, a region of the brain that is known to be critical in the formation of new long-term memories about experienced events (episodic/autobiographical memory). Persons with lesions in the hippocampus, which can occur by a trauma to the head, are unable to form new long-term memories, in a condition known as anterograde amnesia, which was portrayed in the movie “Memento” (2001).
The BMES-ERC design of the cortical prosthesis features a MEA connects one region of the hippocampus to another, bypassing the location of the lesion. The device works by recording the collective activities of underlying neurons in one region, processing them, and generating electrical pulses at a second region. Currently, the device is being geared to replace the function of the Schaffer collaterals, an area connecting CA3 region of the hippocampus to CA1 region.
Similarly to any long-term implants, the biotic-abiotic interface is an important issue to address for the cortical prosthesis. Particular for this prosthesis is the need to provide bi-directional communication between the prosthesis and the surrounding neurons, requiring more demands than just a mechanical fixation. The penetrable MEA will have two basic types of materials—a conductive electrode pad and an insulating support—that need to attach with different characteristics to its surrounding tissue.
We have observed that covalently bound cell adhesion molecules (CAMs) on both conducting and insulating surfaces will promote neuronal cell adhesion. Currently, we are investigating the effect of CAM density on the surface and the length of the linker between the surface and the CAMs towards neuronal adhesion and the formation of cellular network. We are also working on applying our approach for temperature-dependent tissue adhesion from the retinal prosthesis project for possible applications in cortical prosthesis.