Multifunctional Grooved Microtubes with Genetic Patterning for Directional Nerve Cell Alignment and Inflammation Control

Peripheral nerve injury (PNI) represents a common disability worldwide and may lead to enduring disabilities without appropriate interventions. The need for PNI treatment underscores the necessity for efficient regeneration methods. Among diverse candidates, microtubes as nerve conduits demonstrate great promise due to their ability to guide cell migration, and promote axon elongation at injury sites. Besides many commercially available microtubes, marvelous efforts are devoted to mimicking the native extracellular matrix through intricate microtube designs and the integration of functional payloads. However, the complicated design and fabrication process in grooved patterning and the incorporation of bioactive additives costs significant time and effort. Additionally, challenges remain in achieving spatiotemporal encapsulation and controlled release of payloads. Thus, a sophisticated yet feasible design is highly anticipated.
Harnessing my solid background in microfluidic spinning of microfibers and their biomedical applications including PNI treatment, I have successfully fabricated microfibers with designed morphologies and the spatial encapsulation and controllable release of different payloads and also demonstrated their efficacy in peripheral nerve repair. Additionally, I have also developed a nerve-on-a-chip platform to assess the preclinical performance of microfibers in PNI treatment.
Consequently, in this project, I will continue my persistent work to advance the biomimicry of microtubes and improve their biological functions for peripheral nerve regeneration. Employing microfluidic spinning, both grooved and genetic patterning of microtubes can be realized where coherent sacrificing flows formed the grooves and nanoparticles assembled by miRNA will be in situ synthesized and encapsulated. The grooved patterning is in favor of cell alignment and axon elongation; while the released miRNA-based nanoparticles are expected to promote M1 to M2 macrophage polarization, and induce the transformation of Schwann cells to a repair phenotype, thus facilitating the functional rehabilitation of the peripheral nerve. Such microtubes may efficiently provide orientational guidance for axon extension and contribute to reconstructing the microenvironment during nerve repair. This study holds fundamental significance for PNI research, as well as the development of functional microtubes for related disease treatments.