MARC 主機 00000nam  2200397   4500 
001    AAI3369764 
005    20110712090411.5 
008    110712s2009    ||||||||||||||||| ||eng d 
020    9781109323535 
035    (UMI)AAI3369764 
040    UMI|cUMI 
100 1  Saeidi, Nima 
245 10 On the control of collagen fibril organization and 
300    185 p 
500    Source: Dissertation Abstracts International, Volume: 70-
       08, Section: B, page: 4987 
500    Adviser: Jeffrey W. Ruberti 
502    Thesis (Ph.D.)--Northeastern University, 2009 
520    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 
520    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 
590    School code: 0160 
650  4 Engineering, Biomedical 
650  4 Engineering, Chemical 
650  4 Engineering, Mechanical 
690    0541 
690    0542 
690    0548 
710 2  Northeastern University.|bMechanical and Industrial 
773 0  |tDissertation Abstracts International|g70-08B 
856 40 |u