SBIR Phase I: Nanofibrillar Scaffolds for Tissue Engineering

This Small Business Innovation Research Phase I project will investigate manufacturability of the proposed innovation in the field of tissue engineering, overcome related research challenges, and estimate the market opportunity. We have developed, tested and patented novel process to induce self-assembly of molecular collagen into a number of collagen scaffolds with the organizations found in human tissues. The process is computer controlled and highly reproducible. The scaffolds with aligned-crimp fibrils have been implanted with and without cells into animals and have been found to induce the formation of new functional vasculature mostly aligned along the fibrils and maintain implanted cells viable for extended times in the ischemic tissue. We believe that our scaffolds could improve vascular function in conditions such as lymphedema and peripheral ischemia and be adaptable for diverse uses in tissue engineering. Therefore the goal of the project is to focus on the development of scalable manufacturing process for the preparation of nanofibrillar collagen scaffolds in a thread-like multi-luminal format and test them in-vitro and in-vivo in suitable animal models with and without plated cells. Scale-up system will include a novel collagen delivery device, semi-automated tooling to manufacture longer threads and both optical and laser inspection tools. The broader impact/commercial potential of this project is based on the nature of our platform technology. Many current repair operations, such as rotator cuff repair and ligament replacement, use cadaver derived materials. Utilizing our approach, we can produce safe, strong, biocompatible replacements whose dimensions match those of the patient. Further, our materials should be less expensive. Stem cell applications in regenerative medicine have been limited by poor survival and lack of retention in target tissue. When delivered on our multi-luminal thread-like scaffolds, we achieve good survival and localization with the potential to enhance repair and facilitate stem cell application. The issue of cell and material retention in injectable gels, as well as vascularization and nutrient diffusion in three-dimensional scaffolds, remains a challenge. Advantages of our thread-like scaffolds are: large surface area for cell attachment due to their open, multi-luminal structure; fibril alignment directing cell alignment and migration; extended survival and maintenance of cells implanted on the threads; tunable mechanical properties to achieve the desired function and persistence. Our scaffolds will be used alone as well as loaded with cells for repair and regeneration of vascular and lymphatic systems and represent a significant step toward a major unmet medical need.