Designing a nerve tissue scaffold of tunable stiffness from natural biomaterials

Traumatic damage to the nervous system severs axons and causes disabling injury. Regenerative therapies are being designed to encourage regain of function. However, limitations in regeneration present challenges to tissue engineering therapies for neural trauma. Neuronal growth is affected by many properties of the local environment, including chemical and mechanical interactions between neurites and the substrate. Most experiments in this field have controlled biomaterial properties using reactive aldehydes unsuitable for use in vivo. Instead, we evaluate the use of a biocompatible crosslinking agent, genipin, of natural origin. Chitosan, an established biopolymer, formed the backbone of our tissue scaffolds. By varying the chitosan:genipin ratio, we were able to create hydrogels of tunable stiffness to examine the effect on neuronal regeneration. Using cell culture and rheological techniques, we have characterized these chitosan-genipin biomaterials and observed preferential adherence to substrates of similar properties to native nerve. These findings suggest that genipin loaded chitosan gels can be used as a viable substrate for nerve growth and repair.