ERI: Investigating Scaffold Degradation for Peripheral Nerve Regeneration: From Mechanism to in vivo Application

About This Grant

Serious injuries to nerves lead to disabilities that make it hard for people to move or sense touch. One way to help nerves heal is by using tissue scaffolds, which are tube shaped structures that act as bridges to reconnect damaged nerves. However, scaffolds do not always work as well as desired because they interact in complex ways with the nerves, and these interactions are not fully understood. This research focuses on how scaffolds degrade over time and how that affects nerve healing. The goal of this project is to find better ways to control degradation so that scaffolds can support nerve repair more effectively. To do this, a special printing technique called 3D bioprinting will be used to create scaffolds with precise shapes and structures. Then, scaffold degradation and effects on nerve healing will be studied. By determining how scaffold breakdown influences nerve growth and healing, better scaffolds to improve nerve repair can be designed and developed, which can help patients with nerve injuries. Undergraduate and graduate students involved in the project will receive hands-on training, strengthening the workforce in biomanufacturing and regenerative medicine. This project will also feature interactive outreach activities for local high school students through various programs to expand the next generation of science and engineering workforce. Scaffolding strategies for repairing injured peripheral nerves with critical nerve gaps remain a significant challenge. Limited regeneration is primarily attributed to the intricate interactions between nerve tissue and scaffolds, which are inherently complex and not yet fully understood, particularly concerning scaffold degradation. While degradable scaffolds are generally associated with superior nerve regeneration compared to non-degradable ones, the underlying mechanisms linking scaffold degradation to enhanced peripheral nerve repair remain insufficiently elucidated. Specifically, the optimal degradation rates that facilitate changes in porous structures to support nerve regeneration have yet to be determined. This research aims to elucidate the influence of material composition and structural design on the degradation of bioprinted tissue scaffolds and establish the mechanistic connections between degradation and peripheral nerve regeneration. First, a comprehensive analysis will be conducted to determine how scaffold material composition and structural design influence degradation, and the subsequent impact on Schwann cell functionality—the key supporting cells in the peripheral nervous system—will be quantified. Next, scaffold degradation will be assessed in vivo using non-invasive imaging techniques, enabling a comprehensive evaluation of its relationship with sciatic nerve regeneration in a rat model. This research will provide critical mechanistic insights into the role of scaffold degradation in nerve repair and introduce innovative methodologies for quantifying scaffold integrity both in vitro and in vivo, advancing peripheral nerve treatment strategies. 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.