Our research group is also designing tissue scaffolds that can facilitate the growth of peripheral and spinal cord axons. In this work, we are using naturally-derived hyaluronan, which is a sugar molecule found in all of our bodies. This sugar molecule is non-immunogenic (i.e., not rejected) and plays a major role in wound healing and development of embryos, and is therefore exciting as a material to promote the natural wound healing cascade as part of nerve repair. Our group has devised novel techniques to process this sugar material into forms that can be used in therapeutic applications. For example, we are using advanced laser-based processes to create “lines” of specific proteins within the hyaluronan materials to provide physical and chemical guidance features for the individual re-growing axons. We have found that these materials facilitate neuron interactions and are thus highly promising for regenerating peripheral and spinal nerves in vivo. The design of these advanced materials for nerve regeneration relies on a strong understanding of chemistry and materials science, as well as the biological knowledge of how neurons regenerate in the body and how neurons interact with materials.
In a parallel approach to foster nerve regeneration, our group has developed natural tissue scaffolds termed “acellular tissue grafts” created by chemical processing of normal intact nerve tissue. These grafts are created from natural biological tissue — human cadaver nerves — and are chemically processed so that they do not cause an immune response and are therefore not rejected in patients. These grafts have been optimized to maintain the natural intricate architecture of the nerve pathways, and thus, they are ideal for promoting the re-growth of damaged axons across lesions. These engineered, biological nerve grafts are used in the clinic and are an example of how our research is promoting the development of biomedical products that can improve human health.
Better technologies to aid nerve regeneration and to communicate with neurons require better biomaterials that both physically support tissue growth and elicit desired cellular-specific responses. We are working with electroactive polymers with inherent properties that can stimulate electrically responsive cell types such as nerves. Using these polymers, our group has created new biomimetic, electronic materials by processing electrically conducting polymer composites (e.g., polypyrrole) into 3D fiber matrices for enhanced topographical guidance and by incorporating biological moieties using novel peptides that directly bind to conducting polymers (uniquely selected using advanced processes such as phage display). Ultimately, these materials can be used to interface with neurons for electronic communication or as internal “pathways” to physically guide and to electrically, chemically and biologically stimulate the neurons to grow.
Our group is also interested in the mechanisms of axon extension, and in particular how neurons make decisions between different types of environmental and biological stimuli, so that we can better design therapies for nerve repair. In particular, we have created microfabricated cell analysis devices for testing how neurons respond to signals (physical signals in the form of microgrooves, chemical cues in the form of immobilized growth factors, and electrical signals in the form of conducting polymers) both in combination and in competition. We have found distinct differences in how cells respond to physical versus chemical guidance cues presented simultaneously, and found that these responses depend on the growth/differentiation stage of the neuron (axon formation versus steady-state axon elongation). It appears that neurons particularly favor topographical or physical features over chemical features when forming axons. This information is proving useful by steering our research group to focus on therapeutic devices that provide physical (topographical) features to enhance the initial formation of axons in regenerating peripheral and spinal cord nerve tissue. We are also using other experimental and modeling approaches to understand how cells migrate in response to additional signals, such as electrical stimulation and to understand how affinity peptides bind to conducting polymers.