Anatomically Inspired Scaffold Design Enhances Tissue Regeneration in Brain and Spinal Cord.

Abstract

Because traumatic damage to the central nervous system (CNS) has no clinical cure, various reparative strategies are under scientific investigation. Current literature in CNS regeneration focuses largely on three components: biomaterials, neurotrophic factors, and cells. Though researchers agree the ultimate treatment will be a combination, the effects of individual components should be understood to maximize effectiveness. Biomaterials are viewed mainly as delivery vehicles. The macro-scale architectures, shapes and features above 100 micron size, are not diversely investigated. Single and multi-channeled guidance tubes are the most common macro-architectures for spinal cord studies. Treatments for brain injury have not used macro-architecture. Though the macro-architectural influence is unknown, the relative ease of architectural manipulation makes it an attractive path to improve regeneration in the CNS by potentially enhancing the effects of other components. Use of effective architectures could potentially decrease dose requirements for expensive or limited treatments such as recombinant proteins or autologous cells. It is thus hypothesized that creating a more diverse set of macro-architectures based on known anatomical characteristics of the tissue would improve the regenerative capacity of the CNS. To test this hypothesis macro-architectural designs were created based on known anatomical architectures in cerebral cortex and spinal cord. Designs were converted into molds on a 3-D printer and salt-leached degradable polymer scaffolds were fabricated by indirect solid free-form fabrication (SFF). Channels and microgrooves were incorporated into a cylindrical scaffold and implanted into a rat cerebral cortex defect. Results demonstrate that interconnecting channels and microgrooves oriented in the direction of desired migration enhance regeneration into a porous scaffold. For the spinal cord, five architectures were designed for a complete transection, two of which were aimed at reducing circumferential barriers to regeneration and providing medial support for white matter tracts. Implantation of these two new designs and three conventional designs shows that the new designs improve integration of neural tissue and suppress secondary damage in the gray matter. These are the first in vivo experiments using scaffolds made by indirect SFF techniques having designed architectures in CNS regeneration. Effectively designed macro-scale architectures can improve tissue regeneration in the CNS.