Because traumatic damage to the central nervous system (CNS) has no clinicalcure, various reparative strategies are under scientific investigation. Currentliterature in CNS regeneration focuses largely on three components: biomaterials,neurotrophic factors, and cells. Though researchers agree the ultimate treatmentwill be a combination, the effects of individual components should be understood tomaximize effectiveness.Biomaterials are viewed mainly as delivery vehicles. The macro-scale architectures,shapes and features above 100 micron size, are not diversely investigated. Singleand multi-channeled guidance tubes are the most common macro-architecturesfor spinal cord studies. Treatments for brain injury have not used macro-architecture.Though the macro-architectural influence is unknown, the relative ease of architecturalmanipulation makes it an attractive path to improve regeneration in the CNS bypotentially enhancing the effects of other components. Use of effective architecturescould potentially decrease dose requirements for expensive or limited treatments suchas recombinant proteins or autologous cells. It is thus hypothesized that creating amore diverse set of macro-architectures based on known anatomical characteristicsof the tissue would improve the regenerative capacity of the CNS.To test this hypothesis macro-architectural designs were created based on knownanatomical architectures in cerebral cortex and spinal cord. Designs were convertedinto molds on a 3-D printer and salt-leached degradable polymer scaffolds were fabricatedby indirect solid free-form fabrication (SFF).Channels and microgrooves were incorporated into a cylindrical scaffold and implantedinto a rat cerebral cortex defect. Results demonstrate that interconnectingchannels and microgrooves oriented in the direction of desired migration enhanceregeneration 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 andproviding medial support for white matter tracts. Implantation of these two new designsand three conventional designs shows that the new designs improve integrationof neural tissue and suppress secondary damage in the gray matter.These are the first in vivo experiments using scaffolds made by indirect SFFtechniques having designed architectures in CNS regeneration. Effectively designedmacro-scale architectures can improve tissue regeneration in the CNS.
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Anatomically Inspired Scaffold Design Enhances Tissue Regeneration in Brain and Spinal Cord.