Abnormal angiogenesis-the growth of new blood vessels from existing vasculature-plays a central role in more than seventy major health conditions, afflicting over one billion people worldwide. Uncovering the mechanisms that control angiogenesis promises to fuel the discovery of novel therapies targeting cancer, diabetes, macular degeneration and others-but the progress in translation from basic research into the clinic is slowed by the lack of dependable models for angiogenesis research and drug testing. None of the existing in-vitro models includes the growth of capillary sprouts from existing blood vessels under flow-which is, by definition, the hallmark of angiogenesis. To address this need, our company has developed a proprietary technology for the creation of human microvasculature within microfluidic chips. Within these chips, we generate lumenally perfused 'parent'vessels from human endothelial cells that are surrounded by an extracellular-matrix gel. When exposed to vascular growth factors the parent vessels exhibit angiogenic sprouting and grow new capillaries into the surrounding matrix. We plan to commercialize this technology under the name PIVA (Perfused In Vitro Angiogenesis) system. PIVA is envisioned to consist of the following components: (1) disposable microfluidic chips, (2) portable, modular perfusion platforms that can be stacked inside standard cell incubators, (3) scalable meta-modules that can support up to six microfluidic chips, and (4) image analysis software. The meta-module concept will allow users to run 100 or more assays simultaneously per incubator-a throughput capacity that is sufficient for applications in research and drug discovery. During Phase I of this project, we established feasibility of the manufacturing techniques, developed the prototype of a pneumatically driven perfusion platform and validated that our angiogenesis model recapitulates features of in vivo microvasculature. Currently, chips and perfusion platforms are tested in more than ten research laboratories throughout the U.S. The goal of Phase II is to finish the development of the PIVA technology to enable a rapid commercial transition into the research market.
Aim 1 is to finalize the design of the microfluidic chip, meta-module perfusion platform, and the image analysis software.
Aim 2 will focus on defining assay parameters and establishing the metrics for image analysis and methods for downstream analysis.
Aim 3 will be to test PIVA on drugs with known anti-angiogenic effects. Once Phase II is completed, the PIVA design will be ready for production transfer within twelve months. Nortis has significant expertise in bringing prototype technologies to market. The commercial launch of the PIVA components will leverage previously validated manufacturing processes as well as operational and business infrastructure to support commercial activities. Phase III funding is lined up in the form of angel investments and revenue obtained through sales of existing Nortis products. We believe that PIVA will become an important new tool in angiogenesis research, accelerating the discovery and clinical translation of novel angiogenesis-modulating therapeutics.

Public Health Relevance

Abnormal growth of blood vessels is involved in cancer and many other important diseases. More reliable in- vitro models for the study of vascular growth are needed to accelerate promising drug candidates into the clinic. We have developed a new model that replicates a number of key vascular functions in vitro. Our model provides an important alternative to current in-vitro models and animal testing.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
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Special Emphasis Panel (ZRG1)
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Lundberg, Martha
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Nortis, Inc.
Gig Harbor
United States
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