Open Competition 4 - Biotechnology

Living Vascular Implant

Sponsor: NanoMatrix, Inc.

• Project Performance Period: 6/1/2002 - 5/31/2005
• Total project (est.): $2,593,500.00
• Requested ATP funds: $1,982,500.00

More than 1.4 million surgical procedures that require arterial prostheses are performed each year in the United States, approximately 500,000 of these are coronary artery bypass operations. Because there are no acceptable synthetic prostheses for small-diameter blood vessels, surgeons must harvest the patient's own blood vessels for the transplant. This procedure is time-consuming, prone to complications, and greatly increases the recovery time for the patient. It also limits the number of patients who are good candidates for the surgery, because there are only a few vessels in the body potentially available for transplantation. Attempts have been made for years to develop a viable synthetic or tissue-engineered prostheses for small blood vessels, but all have had high failure rates for one reason or another. To answer this need, NanoMatrix proposes a three-year project to design and fabricate three-dimensional (3D) "scaffolds" out of collagen, the body's natural structural material, that can be seeded with various types of cells to mimic natural, small-diameter blood vessels. Studies suggest that muscle cells, once implanted in the scaffold, will develop the function, shape, morphology, and cellular architecture of the "normal" vessel. In practice, natural blood vessels are difficult to mimic -- they are composed of three distinct layers of different types of cells and attempts to artificially create the blood-vessel tube have been frustrating. NanoMatrix's innovation is a novel "electrospinning" technology to produce nanofibers from collagen and other biological proteins, together with a special bioreactor to culture the implanted cells on this scaffold of collagen. Electrospinning has been used in the past to produce very fine fibers of polymers -- and even collagen -- but lacking precise, controlled orientation of the fibers. NanoMatrix will design and build an electrospinning device that incorporates computerized, multi-axis controls to build collagen scaffolds with the proper layering and orientation to mimic blood vessels. A novel cell culture bioreactor will maintain the constructs and prevent necrosis as the cells grow. Human endothelial cells, smooth muscle cells, and fibroblasts will be used in the inner, middle, and outer layers, respectively, of the vascular constructs. A key challenge will be to achieve the proper alignment, architecture, abundance of cell types, and behavior in each cell layer. The company will optimize the structure, mechanical properties, and biological efficacy of the vascular grafts and then conduct implantation studies. Virginia Commonwealth University (Richmond, Va.) will be subcontracted to conduct the tests. ATP support is necessary because the long history of previous failures to develop small artificial blood vessels discourages venture capital. If successfully developed and approved for clinical use, the new technology could replace all other vascular grafts, reduce coronary bypass surgical costs by 10 percent and other hospital costs as well, and improve productivity and quality of life for people who undergo vascular graft procedures. The technology platform also would be applicable to the engineering of skin, cartilage, bone, muscle, heart muscle, neural tissue, and other tissues.

For project information:

Peter J. Stevens, (972) 751-0382
peter_stevens@nanomatrix.biz

ATP Project Manager

Thomas Wiggins, (301) 975-5416
thomas.wiggins@nist.gov