Overview of NeuSTEM Research

The NeuSTEM lab focuses on the integration of neural engineering with immune and vascular engineering, as recent studies have begun to demonstrate that less well-studied extrinsic barriers to nerve regeneration, such as inflammation and hypoxia, synergize with the intrinsic barriers to prevent nerve repair. The goal of our research is to utilize mulicellular approaches to develop new therapeutic interventions (stem cells, biomaterials, drug delivery, gene therapies) that create a more conducive microenvironment that supports both endogenous and exogenous repair mechanisms.

Biomaterial Approaches for Spinal Cord Repair

Biomaterials are an attraction therapeutic option following injury to the nervous system. In many cases, biomaterial implants can be designed as off-the-shelf products, readily available for surgeons. Biomaterials for nerve repair fall into two large umbrella categories: scaffolds and hydrogels. In our lab, we employ hydrogels that can be polymerized at the injury site, as well as modular hydrogel tubes that can be implanted to fill the injury while also providing directional support. Directional cues are particularly important following spinal cord injury, as axons in the spinal cord are aligned along the longitudinal axis. In the figure below, axon bundles (red) can be observed growing through hydrogel tubes within the injured spinal cord, however very little myelin (green) can be seen insulating the axons. Our lab is currently explore thermoresponsive, self-assembled, and photocurable hydrogel systems for their utility to guide axons, as well as, deliver drugs and/or neural stem cells.

On-Demand Local Drug Delivery for Tissue Engineering

Our team is currently working to develop a synthetic targeting system to serve as an on-demand local drug delivery platform to promote tissue repair. Our system has been designed using a targeting delivery vehicle and a receptor-beacon comprised of synthetic materials so that it can be broadly applied to deliver therapeutics to any tissue. Feasibility of this system has been demonstrated in a cervical spinal cord injury model. The successful completion of this project will result in a drug delivery platform that can facilitate on-demand, local drug delivery for several months after injury and facilitates the localization of repeated dosages at the selected injury site. 

Neural Stem Cell-Mediate Repair

Neural stem cells (NSCs) are a promising therapeutic option to promote regeneration of damaged spinal tissue. However, the regenerative potential of NSCs is severely limited by their poor survival after transplantation into the injury. Because of their poor survival, the long-term benefits of increased NSC transplant survival have not been able to be evaluated. Our group is currently engineering NSCs that are capable surviving after transplantation, but have a controlled "off-switch" to reduce the risk of tumorigenicity. These engineered NSC populations will be purified, expanded as neurospheres, as pictured below, and implanted into the injured rodent spinal cord. Additional projects with NSC transplants are seeking to develop protective biomaterials to deliver NSCs, as well as use these materials to study the regenerative mechanisms of NSCs in vivo.