Agar-based bridges as biocompatible candidates to provide guide cues in spinal cord injury repair

Abstract

Spinal bridge implants are strategic to provide growth surfaces for axonal regeneration after spinal cord injuries. The design of an appropriate substrate, one that is suitable for implantation, must involve careful testing of the biomaterial properties both in vitro and in vivo. The goal of this work was to test the structure, stability and biological response after spinal bridges implantation of several biopolymers, composed of mixtures of agar (AG), as structural matrix scaffold, with κ-carrageenan (Kc), gelatin (G), xanthan gum (Xn) and polysulfone (PS). Biopolymer structures were studied by environmental scanning electron microscopy, whereas the stability of gels was analyzed by in vitro degradation and swelling tests. The biocompatibility of these materials and their ability to promote cell growth and axonal regeneration were studied by implantation of spinal bridges containing empty linear channels in an acute rat spinal cord transection model at thoracic level (T8). All gel mixtures gave rise to porous structures and they were stables to degradation, excepting the AG+G mixture. Spinal bridges constructed from all mixtures were implanted during a month in adult rats. After this time a low host reaction occurred to all bridge materials as well as neurite and cell ingrowths through the empty channels. Neurites within the bridges were mostly peripheral sensory fibers such as those positive for CGRP, whereas there was a lack of regeneration of central axons crossing from the spinal tissue to bridges. Many of these neurites established closed contacts with non-myelin Schwann cells. The histological analysis revealed a high accumulation of collagen fibers within the channels. Unexpected was the apparent loss of channels linearity which affected the growth of neurites and cells, indicating the need for additional regeneration strategies and vertebrae bridge fixing.