Abstract
Peripheral nerve injuries cause different degrees of nerve palsy and function loss. Due to the limitations of autografts, nerve tissue engineering (TE) scaffolds incorporated with various neurotrophic factors and cells have been investigated to promote nerve regeneration. However, the molecular mechanism is still poorly understood. In this study, we co-cultured Schwann cells (SCs) and rat adrenal pheochromocytoma (PC-12) cells on 50% degrees of methacryloyl substitution gelatin methacrylate (GelMA) scaffold. The SCs were encapsulated within the GelMA, and PC-12 cells were on the surface. A 5% GelMA was used as the co-culture scaffold since it better supports SCs proliferation, viability, and myelination and promotes higher neurotrophic factors secretion than 10% GelMA. In the co-culture, PC-12 cells demonstrated a higher cell proliferation rate and axonal extension than culturing without SCs, indicating that the secretion of neurotrophic factors from SCs can stimulate PC-12 growth and axonal outgrowth. The mRNA level for neurotrophic factors of SCs in 5% GelMA was further evaluated. We found significant upregulation when compared with a 2D culture, which suggested that this co-culture system could be a potential scaffold to investigate the mechanism of how SCs affect neuronal behaviors.
Highlights
Millions of people worldwide are injured in traffic, sports, and military accidents every year, which commonly leads to peripheral nerve injuries (PNIs)
This study performed co-cultures of Schwann cells (SCs) and PC-12 cells in the 5% gelatin methacrylate (GelMA) scaffold since 5% GelMA could better support SCs proliferation, viability, and myelination and a higher neurotrophic factors secretion from SCs. These results suggest that SCs dynamically respond to GelMA stiffness, with changes in different DMS (30% and 50%)
PC-12 cells demonstrated a higher cell proliferation rate and axon extension in co-culture, indicating that SCs could stimulate PC-12 growth and axon extension, which could be caused by the secretion of neurotrophic factors from SCs
Summary
Millions of people worldwide are injured in traffic, sports, and military accidents every year, which commonly leads to peripheral nerve injuries (PNIs). Peripheral nerves can generally self-heal from mild and moderate traumas. It generally becomes more complicated when the trauma is greater than 5 mm [3,4]. Autografts is the gold standard for the clinical treatment of PNIs for the past decades due to the low immunogenicity, promotion of cell adhesion and migration, vascularization, and axonal extension. They still suffer limitations, including nerve unavailability, size mismatch, and local tissue adhesion [5,6,7,8], which significantly affect nerve rehabilitation outcomes
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