The proposed work is directed at the commercialization of BMSEED's Micro-Electrode Array Stretching Stimulating und Recording Equipment (MEASSuRE) technology. MEASSuRE bridges the gap between in vitro and in vivo research by simulating the biomechanical and electrical environment of cells in the body in a controlled environment outside of the body. The applications for MEASSuRE fall in two categories: physiological and pathological stretch of cells. In physiological stretch, the cells are stretched within their healthy limits, replicating the complexity of the human body in a controlled in vitro environment. When mechanical stretching or electrical stimulation is applied to human derived stem cells during differentiation, the resulting organs or tissue more closely replicate the complexity of the adult human than the embryonic one, thus (a) increasing the predictive value of toxicity and efficacy drug tests prior to human clinical trials in Organ-on-a-Chip models, and (b) improving the quality of tissue grafts in regenerative medicine applications. In pathological stretch, the cells are stretched beyond the healthy limit, causing a trauma that negatively impacts tissue function or leads to cell death. In traumatic brain injury (TBI) and spinal cord jury (SCI), the primary biomechanical mechanism for the alteration of neural electrophysiology is the deformation of the brain tissue and spinal cord, respectively. MEASSuRE reproduces the biomechanics of a TBI and SCI in a controlled environment in vitro, and the injury level of the stretched neurons can be directly assessed. MEASSuRE could therefore be a screening platform to assess the efficacy of drugs and other treatment strategies for neurotraumatic injuries. The capabilities to mechanically and electrically interface with cells are enabled by incorporating BMSEED's proprietary elastically stretchable microelectrode array (sMEA), which is based on technology patented by Princeton University and exclusively licensed to BMSEED LLC. The goal for Phase I was to develop a commercial process to fabricate the sMEA. The goal of Phase II is to integrate the sMEA with the required hardware to develop MEASSuRE as a complete, convenient, and efficient system. Specifically, this proposal has three aims. The first specific aim is the development and bench-testing of an engineering prototype of MEASSuRE. The focus of this aim is to ensure the components in the MEASSuRE prototype work together smoothly. This work will be carried out in the BMSEED laboratory. The second specific aim is the validation of MEASSuRE for the TBI application using hippocampal tissue slices. The performance of MEASSuRE will be validated and compared against industry standards at the Morrison Neurotrauma and Repair Laboratory at Columbia University. The third specific aim is to conduct product prototype testing of MEASSuRE. Three independent laboratories will evaluate MEASSuRE for different applications: (1) TBI research with cell cultures, (2) regenerative medicine using cardiomyocytes, and (3) SCI research with tissue slices. At the end of Phase II, BMSEED will have validated MEASSuRE for regenerative medicine, TBI and SCI research applications. MEASSuRE will be ready for the marketplace.
This work proposes the commercialization of a research tool that bridges the gap between in vitro and in vivo research by reproducing the biomechanical and electrical environment of cells in the body in a controlled environment outside of the body. This capability will allow researchers to reproducibly simulate a traumatic brain injury, repeated concussions, or a spinal cord injury, and assess the efficacy of drugs and other treatment strategies to mitigate the injury. This new tool will also contribute to increasing the efficiency of pre-clinical drug testing and to provide increased versatility to regenerative medicine applications.
