Prevascularized Scaffolds Bearing Human Dental Pulp Stem Cells for Treating Complete Spinal Cord Injury

Abstract The regeneration of injured spinal cord is hampered by the lack of vascular supply and neurotrophic support. Transplanting tissue‐engineered constructs with developed vascular networks and neurotrophic factors, and further understanding the pattern of vessel growth in the remodeled spinal cord tissue are greatly desired. To this end, highly vascularized scaffolds embedded with human dental pulp stem cells (DPSCs) are fabricated, which possess paracrine‐mediated angiogenic and neuroregenerative potentials. The potent pro‐angiogenic effect of the prevascularized scaffolds is first demonstrated in a rat femoral bundle model, showing robust vessel growth and blood perfusion induced within these scaffolds postimplantation, as evidenced by laser speckle contrast imaging and 3D microCT dual imaging modalities. More importantly, in a rat complete spinal cord transection model, the implantation of these scaffolds to the injured spinal cords can also promote revascularization, as well as axon regeneration, myelin deposition, and sensory recovery. Furthermore, 3D microCT imaging and novel morphometric analysis on the remodeled spinal cord tissue demonstrate substantial regenerated vessels, more significantly in the sensory tract regions, which correlates with behavioral recovery following prevascularization treatment. Taken together, prevascularized DPSC‐embedded constructs bear angiogenic and neurotrophic potentials, capable of augmenting and modulating SCI repair.