Dipankar Dutta

Extracellular vesicles (EVs) represent an emerging class of therapeutics with significant potential and broad applicability. However, a general limitation is their rapid clearance after administration. Thus, methods to enable sustained EV release are of great potential value. Here, we demonstrate that EVs from mesenchymal stem/stromal cells (MSCs) can be incorporated into 3D-printed gelatin methacrylate (GelMA) hydrogel bioink, and that the initial burst release of EVs can be reduced by increasing the concentration of crosslinker during gelation. Further, the data show that MSC EV bioactivity in an endothelial gap closure assay is retained after the 3D printing and photocrosslinking processes. Our group previously showed that MSC EV bioactivity in this assay correlates with pro-angiogenic bioactivity in vivo, thus these results indicate therapeutic potential of MSC EV-laden GelMA bioinks.

Traumatic brain injury (TBI) affects 5.3 million Americans annually. Despite the many long-term deficits associated with TBI, there currently are no clinically available therapies that directly address the underlying pathologies contributing to these deficits. Preclinical studies have investigated various therapeutic approaches for TBI: two such approaches are stem cell transplantation and delivery of bioactive factors to mitigate the biochemical insult affiliated with TBI. However, success with either of these approaches has been limited largely due to the complexity of the injury microenvironment. As such, this review outlines the many factors of the injury microenvironment that mediate endogenous neural regeneration after TBI and the corresponding bioengineering approaches that harness these inherent signaling mechanisms to further amplify regenerative efforts.