Abstract

Overcoming axon regeneration failure after spinal cord injury (SCI) has been a longstanding problem due to i) an incomplete mechanistic understanding of reasons why axons fail to regenerate and ii) technology capable of probing this question in vivo. Regeneration failure has classically been attributed to a combination of glial inhibition and poor neuronal growth capacity, but the degree to which each of these might contribute has been incompletely understood. Advances in genetic engineering and biomaterial development have given us tools to investigate this question in vivo. In this lecture, I will discuss the importance of using engineering strategies to identify and overcome regeneration failure after SCI . This approach has led to the following findings: i) the beneficial role of astrocyte scar formation in CNS axon regeneration, and ii) the development of a mechanism- based biological repair strategy to induce robust regeneration of propriospinal neurons into and past sites of anatomically complete SCI . However, many biological and engineering questions remain regarding modalities to integrate these axons into existing locomotor circuits to foster functional recovery after severe SCI . I will discuss these aforementioned issues and propose potential solutions, including ways to expand this repair strategy to other neuronal populations and techniques to use neuroprosthetic rehabilitation in order to integrate, tune and functionalize regenerating axons.