Bioprinted Tissue Scaffolds with Schwann Cell Density Gradients and Electrical Conductivity for Peripheral Nerve Regeneration

Peripheral nerve injury is a serious health condition that leads to major disabilities. The use of engineered tissue scaffolds offers a promising approach to bridge nerve gaps in the injured nerves for repair. However, the effectiveness of the scaffolds is significantly reduced when these nerve gaps are large, presenting a major challenge in tissue repair.

This is in part because current scaffolds are lacking crucial properties that facilitate nerve regrowth. Electrical signals are vital for nerve reconnections as well as the presence of Schwann cells (SCs), which are the primary support cells in peripheral nerves and release growth factors to help neural axons regrow. Therefore, integration of these two components into a scaffold should improve the effectiveness for peripheral nerve regeneration.

This research focuses on designing scaffolds that combine electrically conductive materials with SCs controlled in a gradient pattern, with the aim of understanding how the level of electrical conductivity and SC distribution enhance peripheral nerve regeneration. Scaffolds with these features will be fabricated using bioprinting techniques to achieve high structural precision, and then their efficacy will be tested in promoting the repair of injured nerves.

The broader impact of this project will inspire new ideas of scaffold design, and advance scaffold-based treatments for nerve regeneration. This work will provide training opportunities for undergraduate and graduate students from diverse backgrounds, contributing to workforce development in biomanufacturing and regenerative medicine in Northeast Ohio.

Additionally, this project will feature interactive outreach activities for local high school students in Cleveland through various programs in an effort to develop the next-generation of science and engineering workforce.

Compelling evidence suggests that integrating electrical conductivity and neurotrophic growth factors with concentration gradients into scaffolds enhances axonal regrowth. This points to the potential of incorporating Schwann cell (SC) density gradients into electrically conductive scaffolds, as SCs arranged in a gradient may produce neurotrophic factors in a similar pattern.

However, the quest for electrically conductive scaffolds capable of supporting SCs arranged in a density gradient remains elusive. The goal of this proposal is to decipher how SC density gradients and electrical properties within tissue scaffolds foster the regeneration of injured peripheral nerves. First, the influence of SC density gradients on axonal regrowth will be determined by bioprinting SC-encapsulated hydrogels, with their impact on neurotrophic growth factor expression and axonal extension being quantitatively measured.

Next, hydrogel substrates incorporating organic color center-modified single-wall carbon nanotubes (OCC-SWCNTs) will be developed to explore how scaffold electrical conductivity affects neural axon growth. Subsequently, electrically conductive scaffolds featuring SC density gradients will be bioprinted, and their performance in promoting the regeneration of injured sciatic nerves in rat models will be evaluated.

This research will provide mechanistic insights into the roles of SC gradients and electrical properties in promoting axonal regeneration, advance SC-based therapies in nerve tissue engineering, and introduce novel bioprinting techniques and materials for peripheral nerve repair. These findings are expected to significantly enhance knowledge and methodologies in scaffolding techniques for peripheral nerve treatment.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.