GOALI: Engineering an In Vitro Assembled Corneal Stroma

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0854023MatthewsSummary: The investigators seek to develop an in vitro assembled corneal stroma for eventual use as a replacement tissue to aid the visually impaired. The work is motivated by the ability to assemble collagen fibrils derived from Cucumaria frondosa into mimics of corneal stroma, a technique which already exists within the team. Extension of this ability to mammalian materials is an overarching goal. The research outcomes expected from the proposed work center around defining the principles by which the collagen scaffolds of extracellular matrices (ECMs) and connective tissues may be assembled for application to tissue engineering. Despite the vast amounts of data available on the mechanical properties of the macroscopic constructs formed by collagen, little is known of the mechanics at the level of the collagen molecule or fibril. These properties will be measured, as well as the interactions between the proteoglycan components of the relevant ECM, providing the information needed to rationally design in vitro equivalents of the tissue. Mechanically matching the materials used in the construction of the stroma to those of the native system will be done at the macromolecular and macroscopic scales. Through this university-industrial collaborative research project with MiMedx, Inc., the team has access to collagens and to a wealth of experience in collagen assembly and applications to tissue engineering. Additionally, the industrial collaboration provides a streamlined mechanism by which the research outcomes will be translated into patient oriented products. Intellectual Merit: The intellectual merit is threefold. 1. For the first time, the mechanics of and interactions between the constituents of collagenous tissues will be systematically and comprehensively explored on multiple length scales, providing a complete picture of how the mechanical properties of filamentous self-organizing systems, in particular type I collagen, are derived. 2. The results will resolve the important question of how load is supported within collagenous tissues. 3. The results also will resolve how the collagen hierarchal forms are established and maintained. Broader Impacts: 1. The results themselves will benefit those endeavoring to a. develop biomimetic materials for connective tissues, b. develop materials for use as scaffolds in tissue engineering, and c. rationally design self-organizing, three-dimensional systems constructed from nanoscale building blocks. 2. The work is highly interdisciplinary, and as such draws students with interest in biomedical engineering, material science, physics, biology, and biochemistry. The ability to recruit students from underrepresented groups is enhanced by this breadth. 3. The laboratories consist of graduate, undergraduate, and high school students. These students will have the opportunity to work jointly in an academic and an industrial setting. 4. An outreach project has been established in which the principal investigator provides young students (K-12) within the US and abroad the opportunity to participate in research experiments by remotely accessing the instrumentation from their own classroom. 5. A new interface for the atomic force microscope is being developed which will allow the visually impaired to perform force spectroscopy experiments. 6. Finally, the material under study has tremendous potential for societal benefit in its applications as a cornea replacement.