Structural Reconstruction of Spinal Cord White Matter Using a Biomimetic Zoned Fiber-Hydrogel Scaffold

Following spinal cord injury (SCI), the zonal architecture of gray and white matter remains challenging to reconstruct. The present study explores a strategy for reconstructing this zonal structure via the integration of oriented fibers with hydrogels. The silk fibers were rationally arranged to conform to the morphological features of the white matter. The incorporation of the hydrogel, in turn, filled the gray matter regions and immobilized the spatial distribution of the fibers. This Gray/White Matter Zoned Scaffold (GWZS) effectively mimics the inherent characteristics of native spinal cord gray and white matter. When dorsal root ganglion (DRG) neurons were 3D cultured within this GWZS, gray/white matter-analogous morphogenesis was recapitulated. Specifically, in the gray matter region, neuronal clusters and nerve fiber network-like architectures were formed; in contrast, in the white matter region, oriented axonal bundles were formed. In vivo transplantation of GWZS effectively facilitated the reconstruction of white matter in the spinal cord; however, endogenous neuroregeneration remained deficient in the gray matter region. Overall, this study not only establishes a novel preparation method for oriented fiber-hydrogel composite bionic spinal cord scaffolds but also provides a viable strategy for the reconstruction of white matter architecture following SCI.