Jeffrey W. Ruberti
Seth Fraden, Sinan Muftu, Vickery Trinkaus-Randall
Date of Award
Doctor of Philosophy
Department or Academic Unit
College of Engineering. Department of Mechanical and Industrial Engineering.
Cornea, Liquid-crystal, Organization, self-assembly, Smart Molecules
Collagen--Structure, Tissues--Mechanical properties
Despite the extensive research on the in vitro engineering of load-bearing tissues (i.e. ligament, tendon and cornea) there has been only limited clinical success. Load-bearing biological structures in vertebrate animals have high mechanical strength which is generally the result of their highly-organized extracellular matrix (ECM). Due to its biocompatibility and ability to form polymerized gels around cells in culture, collagen is an attractive candidate for both de novo tissue engineering and as a scaffolding material. 2 or 3D networks of collagen (most possessing little organization) have been extensively used in tissue engineering applications but have not performed well when the target tissue possesses highly-organized ECM. To overcome this limitation, investigators have employed physical or chemical manipulations of collagen molecules to produce 2D aligned arrays of collagen fibrils for use as guiding templates to influence cell behavior and to control subsequent matrix organization. Unfortunately, the organization of the cells and the synthesized ECM is only influenced over short distances from the organized template. Thus there is a need for scaffolds which are organized in 3-dimensions.
The goal this thesis was to investigate the methods to gain control over organization and ultrastructure of collagen fibrils during self-assembly de novo. In chapter two, the real time dynamics of shear-induced collagen self-assembly was investigated. Thin layers of collagen fibrils were produced by subjecting the solution of collagen molecules to shearing flow. The effects of both simple shear flow and confined shear flow on the organization of the collagen fibrils were studied. In the next chapter, by taking advantage of the "liquid crystalline" properties of collagen molecules, highly-organized lamellae of collagen fibrils were produced from a highly-concentrated solution of collagen molecules. Lastly, the mutability of collagen fibrils subsequent to their association with proteoglycans (PGs) and the results of the chemical interaction on matrix stability were investigated.
The driving hypothesis behind this thesis is that ECM is a dynamic, energy driven system. The interactions between collagen molecules and collagen aggregates with other ECM macromolecules (e.g. proteoglycans) progresses such that the energy landscape of the system decreases, resulting in more stable structures. Through gaining control over these interactions we could produce lamellae of collagen fibrils with organization similar to load-bearing tissues.
Saeidi, Nima, "On the control of collagen fibril organization and morphology" (2009). Mechanical Engineering Dissertations. Paper 7. http://hdl.handle.net/2047/d20000060
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