Grant: Discovery Grants Program - Individual

Background and the nature of the work to be done. Spinal cord injury (SCI) and peripheral nerve injury (PNI) due to car accidents, falls, gunshots, stab wounds, etc., result in loss of motor and/or sensory functions, depending on the location and severity of the injury. Current surgical and rehabilitation strategies are not effective in treating SCI and PNI. The poor regeneration of the spinal cord after injury and the lack of suitable nerve grafts to repair PNI demands an alternative strategy. The strategies of biomaterials-assisted tissue regeneration hold great potential, but decades of studies based on conventional biomaterials did not lead to clinical translation. The unmet biomaterial design criteria for neural tissue repair (both spinal cord and peripheral nerves) are (i) biomimetic electrical conductivity of the biodegradable matrix and (ii) directional guidance cues for axon regrowth. Recently, my lab has made conceptual and technological breakthroughs in novel biomaterials design for electrically excitable tissues (muscle and cardiac tissues). Building on recent advances, I propose a paradigm-shifting approach for designing electrically excitable biomaterials that transcend conventional nerve tissue repair and regeneration materials. Why and to whom the research is important. The proposed research brings together biomaterials and biology for nerve injury and repair and leads to a fundamental understanding of the unsolved challenges to functionally restore injured nerve tissues. It also provides a never-before-studied strategy to instruct the stumps (ends) of the injured nerve axons to grow and reconnect so that nerve impulses can be restored. Proposed methods/approach. Learning from developmental biology neurogenesis cues, we will utilize a three-pronged approach. (i) Extract microtubules from brain neurons for guiding the injured nerve stumps to reconnect, (ii) design an electrically conductive component from choline (a precursor of the neuroreceptor acetylcholine), and (iii) chemically modify hyaluronic acid gels. Electrically conductive gels that incorporate microtubules will be fabricated to form nerve-guiding tubes for PNI repair. Injectable gels for SCI repair will also be formulated. The anticipated outcomes. The proposed study is a significant departure from conventional wisdom as I explore the potential of microtubules and choline-derived electrically conductive materials for nerve repair. I anticipate these biomaterials will create a favorable microenvironment for nerve repair after injury. Benefits to the research field and Canada. The proposed research will contribute to advanced engineering solutions to repair SCI and PNI. The novel biomaterials could potentially revolutionize the field by offering enhanced functional neuron regeneration. The results of the proposed studies will create new knowledge in the NSE and bridge the gap in translating biomaterials-based technologies to human health.