This SBIR Phase I project proposes to commercially develop an in vitro (cell culture) platform to enhance the efficiency of drug discovery. Every drug delivered to a human engages the network of blood vessels for delivery to the target tissue or as part of the removal. An essential feature of the blood vessel network is an extensive network of small vessels surrounded by smooth muscle which can contract and dilate to control blood flow, and thus drug delivery. There are no in vitro human platforms that can mimic this biological function, despite the fact that cardiovascular toxicity is the leading cause of failure in clinical trials. As such, a pre-clinical tool to assess vascular toxicity would significantly impact the drug development process. Developing a successful drug averages 10-12 years and nearly $2.6 billion. Despite the fact that ~60% of the total development costs are spent on human clinical trials, fewer than 1 in 10 entering clinical trials will succeed. There is a significant opportunity to improve the accuracy of preclinical drug screening which, in turn, will generate dramatic cost savings and shorten time-to-market. The company's proposed vasoactive human vascular network represents a leap forward in technology to simulate the human response to new and existing drugs. Furthermore, the platform technology has broad future applications including the incorporation of tissue specific function (e.g, human tumor cells) and patient specificity which will further advance drug development and precision medicine.There are currently no in vitro platforms that can mimic vasoconstriction or vasorelaxation, processes which require vasoresponsive smooth muscle cells. Competing technologies line prefabricated tubes or membranes with endothelial cells to mimic the vasculature which will never be able to simulate vasoactivity. Since the company's platform is comprised of living dynamic microvessels, the company is uniquely positioned to create a platform with this functionality. The primary objective is to develop a 3D perfused human vascular network with smooth muscle providing the capacity to characterize vasoactive substances. The company will achieve the primary objective by completing two specific aims: 1) Incorporate human smooth muscle cells into a 3D in vitro vascular network; and 2) Quantify the dose-response of the 3D perfused vessel network to a panel of vasoactive drugs. Achieving vasoactive functionality in an in vitro vascular network will be the first demonstration of this critical biological phenomenon, and will meet an important commercial need in the pharmaceutical industry.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
