Matthew Engel

Minimally Invasive Delivery of Mesenchymal Stems to the Nucleus Pulposus Using an In Situ Thermoresponsive Hydrogel

In July 2009, I passed a major milestone in my graduate research in the Department of Biomedical Engineering at Stony Brook University - I passed my qualifying exam! This literally required hundreds and hundreds of hours of work, during which I read over 50 scientific publications and synthesized them to come up with an original grant proposal. In this case, my challenge was to use a tissue engineering approach to treat degenerative disc disorder. Below, I will place my statement of interest plus a copy of the grant proposal and presentation I made. I most definitely learned a tremendous amount from this process, most of which I will be keeping private and storing away for later use. But it really teaches you how to make an effective presentation and to prepare thoroughly for a talk.

In a nutshell, the project focuses on stem cell implantation technology to treat spinal chord injuries associated with aging, and could also be applied to acute injuries.

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PROJECT SUMMARY: This proposal aims to design an in situ curable hydrogel composed of PNIPAAm-PEG capable of delivering therapeutic cells and drugs to the degenerated nucleus pulposus (NP) of an intervertebral disc (IVD). The therapeutic cells will be human mesenchymal stem cells (hMSCs) differentiated into NP-like cells by exposure to hypoxic low oxygen conditions in the presence of transforming growth factor β1 (TGF- β1). The hydrogel is composed of a solution containing 10% PNIPAAm-PEG(8000) at a 1:1600 ratio of PNIPAAm:PEG which undergoes a sol-gel transition at physiological temperatures (32°C). Modifications to the PEG molecular weight or concentration can be used to alter the hydrogel stiffness or sol-gel transition temperature. These properties will allow users to prepare cell and drug loaded solutions at ambient temperatures and then inject them into the degenerated disc, at which point they solidify in situ. The hydrogel is capable of being blended with small molecule inhibitors of nitric oxide synthase (NOS). The inhibition of NOS has been shown to increase proteoglycan content which can restore disc height to the degenerated IVD.

Download copy of grant proposal here (.pdf)