Physical and biological performance of a novel block copolymer nerve guide.
Although the ability to regenerate is evident in the nervous system, lesioned neurites are unable to cross gaps in neuronal pathways. In order to bridge gaps, guiding cues are essential to direct neurite regrowth. To overcome many of the shortcomings of polymer-based nerve guides, we developed a bioresorbable nerve guide composed of a novel trimethylene carbonate-caprolacton block copolymer (TMC-CL). Pore formation was controlled by using special solvent/precipitation media compositions in combination with the pore forming agent poly ethylene glycol (PEG). NMR spectroscopy, shear force-, compression-, and permeation assays were used for conduit characterization. The polymer conduit has a semipermeable wall with submicron pores to allow free metabolite/drug exchange. In order to investigate the principle of temporally controlled expression of therapeutic proteins in nerve guides, Neuro-2a cells were genetically engineered to express the reporter gene product green fluorescent protein (GFP) under the control of the Tet-On system. When these transduced cells were encapsulated in nerve guides, GFP expression could be induced for days by adding the antibiotic tetracycline derivative doxycycline to the nerve guide environment. Furthermore, encapsulated dorsal root ganglia (DRG) produced long neurites in vitro. In subsequent in vivo experiments, nerve guides filled with Schwann cells (SC) were implanted into lesioned spinal cords of adult rats. Regeneration of spinal cord axons into nerve guides was promoted by co-implanted Schwann cells. The data suggest that the novel TMC-CL nerve guides provide a promising tool for neuroregeneration.