Object: The aim of this study was to compare designed scaffolds with a random-pored sponge scaffold to determine what role scaffold architecture plays in a cortical injury model.
Methods: Cylindrical scaffolds (3x3 mm) were made of a poly-(epsilon-caprolactone) polymer with 2 different molds from a 3D printer and had either: 1) unidirectional channels and microgrooves oriented longitudinally within the cylinder or 2) orthogonally intersecting channels and axial microgrooves within the cylinder. Additional randomized porosity was imparted using a salt-leaching method. A control scaffold without channels or microgrooves but containing random pores was also made. Scaffolds were implanted for 1, 4, and 8 weeks in a cylindrical defect created 3 mm posterior to the bregma in rat cortex. Control animals had tissue removed but received no implant. Brains were coronally cryosectioned and sections were stained. Antibodies for nestin, glial fibrillary acidic protein (GFAP), and TUJ1 were used to identify neural progenitors, activated astrocytes, and neuronal axons. Tissue ingrowth (H & E), astrocytic infiltration (GFAP), parenchymal inflammation (GFAP), and defect width (H & E) were quantified from images.
Results: Defect widths grew and parenchymal inflammation decreased over time with no statistical difference between groups. Total tissue ingrowth and astrocytic infiltration increased over time and was greatest in the orthogonal design group. Specific cell ingrowth, which was aligned with microgrooves interiorly in the orthogonal group and exteriorly in the longitudinal channel group, was qualitatively assessed from nestin and TUJ1 labeling.
Conclusions: Scaffold architecture can benefit brain tissue regeneration by integrating the following design principles: 1) large (100s of micrometers) pores or channels oriented toward the parenchyma for increased astrocytic infiltration; 2) microgrooves oriented in the desired direction of cellular migration and neuronal alignment; and 3) fully interconnecting channels for cellular migration and tissue integration.