Biofabrication and testing of a fully cellular nerve graft

Abstract

Rupture of a nerve is a debilitating injury with devastating consequences for the individual’s quality of life. The gold standard of repair is the use of an autologous graft to bridge the severed nerve ends. Such repair however involves risks due to secondary surgery at the donor site and may result in morbidity and infection. Thus the clinical approach to repair often involves non-cellular solutions, grafts composed of synthetic or natural materials. Here we report on a novel approach to biofabricate fully biological grafts composed exclusively of cells and cell secreted material. To reproducibly and reliably build such grafts of composite geometry we use bioprinting. We test our grafts in a rat sciatic nerve injury model for both motor and sensory function. In particular we compare the regenerative capacity of the biofabricated grafts with that of autologous grafts and grafts made of hollow collagen tubes by measuring the compound action potential (for motor function) and the change in mean arterial blood pressure as consequence of electrically eliciting the somatic pressor reflex. Our results provide evidence that bioprinting is a promising approach to nerve graft fabrication and as a consequence to nerve regeneration.

Principles of the Kenzan Method for Robotic Cell Spheroid-Based Three-Dimensional Bioprinting

“…Some success had the 'organs-on-chip' microfluidic devices 26 , but their scaling-up and integration into functional bioprinted constructs need more efforts to succeed. The same issues apply to the innervation of the bioprinted constructs 27 .…”

Progress in scaffold‐free bioprinting for cardiovascular medicine

“…Then, the hydrogel is dissolved, leaving behind a “scaffold‐free” construct. By this approach, vascular,33 nerve,34 liver35 and kidney36 structures were demonstrated and now commercialized for in vitro pharmacological assays.…”

3D bioprinting for cell culture and tissue fabrication

“…The agarose rods were used as supporting materials and removed after 7 days. Importantly, both motor and sensory function in a rat sciatic nerve injury model were recovered after 40 weeks of implantation of the constructed neural grafts [109]. Lee et al 3D bioprinted a neural tissue model in which rat embryonic neurons and astrocytes were embedded within collagen.…”