Ning Zhang, Ph.D.; Clemson University; TBI Concept Award

We are developing new therapy, clinical applicable therapy, for treatment of TBI. TBI has been associated significantly in the loss of neurons and glia cells at the lesion site. And the people trying to replace the cells that are lost and as a result they transplanted the neurons and glia cells to the TBI lesion site in effort to regenerate normal brain tissue. And because the TBI at the lesion zone is a compromised environment, you know primary injury and the secondary injury, which leads to the release of many toxic compounds and also the scar formation at the lesion zone. That would jeopardize the survival of any transplanted cells. Therefore there is no tissue regeneration at the lesion even with the transplantation strategy. My research is unique because we have developed this biomaterial, which is a hydrogel. It's an injectable hydrogel, biodegradable, and in situ gellable meaning that they could have transformed from a liquid state to a gel at the lesion site. And the hydrogel has multifunctions in the application. One is as a substrate that allows the reconstruction of the blood vessel network, and the other is as a delivery vehicle to deliver biological factors that instructed the neuron genesis response from the brain resident stem cells. So the neuron stem cells are not transplanted, the neuron stem cells reside in the brain that we provided signals-signaling growth factors to instruct them to regenerate neuron tissue at the lesion site. Neuron stem cells originally reside in the subventricular zone in the brain. So what we are trying to do is to mobilize neuron stem cells from the natural reservoir in the subventricular zone and instruct them to slide specifically recruited them to the lesion zone- TBI lesion zone. And then later deliver growth factors to differentiate those migrated neuron stem cells into neurons and glia cells which will repopulate the lesion cavity for the regeneration. And we found that the hydrogel helps maintain a constant level of the vascular and endothelial growth factor which is important to regenerate blood vessels and also to support the maturation and functionality of the formed blood vessels. So this shows that with the hydrogel injection we have reconstructed the complete blood vessel network at 4 weeks after the TBI lesion and we have shown that our hydrogel can be used to deliver a wide spectrum of growth factors such as those and up to months in vivo. And this is a comparison of different strategies at 4 weeks after TBI. When compared to the saline injection control, the injection of hydrogel and hydrogel plus growth factor have structurally repaired the gross defect of the TBI lesion and in particular with the growth factor the lesion site seems to be reduced in size indicating the ability of manipulated neuron stem cells to regenerate neuron tissue at the zone. And depending on the progress, which we are now moving it to primate studies, we could go to the preclinical trial within safely to say 5 years, and this would be very beneficial in sustained functional recovery in the TBI patients.