Spinal cord tissue engineering using human primary neural progenitor cells and astrocytes.

Neural progenitor cell (NPC) transplantation is a promising approach for repairing spinal cord injury (SCI). However, cell survival, maturation and integration after transplantation are still major challenges. Here, we produced a novel centimeter-scale human spinal cord neural tissue (hscNT) construct with human spinal cord neural progenitor cells (hscNPCs) and human spinal cord astrocytes (hscAS) on a linearly ordered collagen scaffold (LOCS). The hscAS promoted hscNPC adhesion, survival and neurite outgrowth on the LOCS, to form a linearly ordered spinal cord-like structure consisting of mature neurons and glia cells. When transplanted into rats with SCI, the hscNT created a favorable microenvironment by inhibiting inflammation and glial scar formation, and promoted neural and vascular regeneration. Notably, the hscNT promoted neural circuit reconstruction and motor functional recovery. Engineered human spinal cord implants containing astrocytes and neurons assembled on axon guidance scaffolds may therefore have potential in the treatment of SCI.

Spinal cord tissue engineering via covalent interaction between biomaterials and cells.

Noncovalent interactions between cells and environmental cues have been recognized as fundamental physiological interactions that regulate cell behavior. However, the effects of the covalent interactions between cells and biomaterials on cell behavior have not been examined. Here, we demonstrate a combined strategy based on covalent conjugation between biomaterials (collagen fibers/lipid nanoparticles) and various cells (exogenous neural progenitor cells/astrocytes/endogenous tissue-resident cells) to promote neural regeneration after spinal cord injury (SCI). We found that metabolic azido-labeled human neural progenitor cells conjugated on dibenzocyclooctyne-modified collagen fibers significantly promoted cell adhesion, spreading, and differentiation compared with noncovalent adhesion. In addition, dibenzocyclooctyne-modified lipid nanoparticles containing edaravone, a well-known ROS scavenger, could target azide-labeled spinal cord tissues or transplanted azide-modified astrocytes to improve the SCI microenvironment. The combined application of these covalent conjugation strategies in a rat SCI model boosted neural regeneration, suggesting that the covalent interactions between cells and biomaterials have great potential for tissue regeneration.