Restoration of function after spinal cord transection using a collagen bridge

Abstract

The restoration of function of transected adult mammalian spinal cord without living tissue has not been reported previously. We report the first success of functional restoration of transected spinal cord without living tissue. We grafted collagen filaments parallel or transverse to the axis of the spinal cord to bridge 5-mm defects of 47 adult rat spinal cords. Twenty-five rats were used as a control. Of the 72 rats, 42 rats survived the experimental period. At 4 weeks postoperatively, regenerated axons crossed the proximal and distal spinal cord-implant interfaces in all 5 rats of the parallel-grafted group. At 12 weeks postoperatively, the rats in the parallel-grafted group (8 rats) could walk, run, and climb with hind-forelimb coordination. The somatosensory-evoked potentials were seen. Results suggest that the collagen filaments support the axonal regeneration of the transected spinal cord and the restoration of function when grafted parallel to the axis of the spinal cord. The functional restoration appeared to be permanent, raising the possibility of therapeutic application in humans.

Bioengineered Strategies for Spinal Cord Repair

“…It is of interest that implantation of collagen rolls enclosing cultured Schwann cells into the cavity of the injured rat spinal cord contributed to axonal regeneration, although only a few axons originating from the host spinal cord were found in the implanted acellular collagen rolls (Paino and Bunge, 1991). Remarkably, a recent report showed that implantation of plain collagen filaments significantly enhanced functional recovery after spinal cord transection; however, the death rate of the animals up to 12 weeks after implantation of collagen filaments was more than 40%, which suggests the possibility of cytotoxicity associated with the grafted collagen filaments (Yoshii et al, 2003a,b;Yoshii et al, 2004). Thus, the promise of collagen for spinal cord repair is somewhat disputed and may depend on the form of collagen used (i.e., tubes vs. filaments) or with what it is combined.…”

One-year clinical study of NeuroRegen scaffold implantation following scar resection in complete chronic spinal cord injury patients

“…Different types of collagen scaffolds have been used to repair SCI in animal models, including collagen tubes, fibers, membranes, and gels. A growing body of work shows that collagen scaffolds are suitable for guiding neural regeneration (Sindou, 2001;Stang et al, 2005;Yoshii et al, 2004). In our previous study, the NeuroRegen scaffold was prepared from bovine aponeurosis, which mainly consists of linearly ordered collagen fibers.…”

Artificial collagen-filament scaffold promotes axon regeneration and long tract reconstruction in a rat model of spinal cord transection

“…It had been reported that various biomaterial scaffolds can be implanted at the site of nerve injury and are effective in promoting nerve regeneration [10,13,14,[19][20][21][22][23][24][25][26][27]. There is an urgent need for scaffolds that are safe and clinically useful, with type I collagen having received the most attention to date.…”

“…In recent studies, we reported that rats with CF grafts could walk, run and climb with hind-forelimb coordination [10,13,14]. Furthermore, this functional restoration appeared to be permanent.…”