Thesis (Ph. D.)--Ohio State University, 2009. / Title from first page of PDF file. Includes bibliographical references (p. 305-320).

Thesis (Ph. D.)--University of Texas at Austin, 2001. / Vita. Includes bibliographical references. Available also from UMI Company.

Thesis (M.S.)--Mechanical Engineering, Georgia Institute of Technology, 2004. / Dr. David Ku, Committee Chair ; Dr. Raymond Vito, Committee Member ; Dr. Alexander Rachev, Committee Member. Includes bibliographical references (leaves 103-106).

Thesis (Ph. D.)--Drexel University, 2004. / Includes abstract and vita. Includes bibliographical references (leaves 168-182).

Thesis (Ph.D.)--University of Delaware, 2009. / Principal faculty advisor: Kristi L. Kiick, Dept. of Materials Science & Engineering. Includes bibliographical references.

Thesis (M.Phil.)--Hong Kong University of Science and Technology, 2003. / Includes bibliographical references (leaves 128-138). Also available in electronic version. Access restricted to campus users.

Thesis (M.S.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2009. / Committee Chair: Weck, Marcus; Committee Member: Collard, David; Committee Member: Kubanek, Julia. Part of the SMARTech Electronic Thesis and Dissertation Collection.

Thesis (Ph. D.)--Biomedical Engineering, Georgia Institute of Technology, 2007. / Committee Chair: Julia Babensee ; Committee Members: Barbara Boyan, John Brash, Andres Garcia, and Niren Murthy. Part of the SMARTech Electronic Thesis and Dissertation Collection.

The golden method of peripheral nerve system injury is the nerve autograft, but it is associated with drawbacks such as donor site morbidity, needs of second incisions and the shortage of nerve grafts. Comparatively, connecting the nerve defect directly is an alternative. Unfortunately, if the defects are long, the induced tension will deteriorate the nerve regeneration. These limitations led to the development of artificial nerve guidance conduit (NGC). The market available NGC have problems of unsatisfactory functional recovery and may collapse after the implantation. These are attributed to material and structural deficiencies. Therefore, there is essential to study a biomaterial, which has excellent biological and physical properties to fit the NGC application. In addition, some studies suggested that the poor functional recovery resulted from the NGC implantation were due to the lack of micro-guidance inside the conduit. Thus, it is necessary to investigate the structural influence on the functional recovery of peripheral nerve injury. Crosslinked urethane-doped polyester elastomer (CUPE) is newly invented for a blood vessel graft because it possesses similar mechanical properties of blood vessel which is similar to nerve as well. Therefore, CUPE was also considered to be the NGC. Its biocompatibility has been proved to be excellent in the previous study done by Dr. Andrew SL, Ip. Targeting on the long peripheral nerve regeneration, the aims of this study are (1) to investigate the biocompatibility of CUPE in in-vitro condition and (2) to study the influence of nerve-like structure on the peripheral nerve system injury in an animal model. The ultimate goal is to enhance the functional recovery of peripheral nerve system injury by implanting a flexible biomaterial, CUPE, which has a nerve-like microarchitecture. It is hypothesized that the nerve-like structure can promote the axonal regeneration. The surface energy and roughness of CUPE were investigated. It showed a relatively low surface energy compared to other conventional biopolymers such that the cell adhesion and also the proliferation were inhibited. Therefore, the CUPE was modified by the immersion into a high glucose DMEM. The change in the hydrophilicity, roughness and cell viability of medium treated CUPE were studied. The hydrophilicity of treated CUPE was increased but the roughness was remaining unchanged whereas the pH of the immersion solution did not cause any effect on the cell activity on the CUPE. In the pilot animal study, five channels along the CUPE-NGC had a similar myelinated fiber density and population compared to the nerve autograft. Also, the channels in the CUPE-NGC were fragmented. In summary, the medium treatment could enhance the hydrophilicity of CUPE and the cell activity on CUPE. Such modifications did not governed by the pH of the medium. The NGC-CUPE with five channels, which imitated a basic nerve structure was shown to have a similar tissue regeneration and the functional recovery as the nerve autograft did. The results proved the hypothesis that the nerve-like structure can promote the functional recovery of peripheral nerve system injury with the use of a new biomaterial, CUPE as the NGC substrate. / published_or_final_version / Orthopaedics and Traumatology / Master / Master of Philosophy

The mission of tissue engineering is to recapitulate the natural process of tissue formation by assembling cells into synthetic scaffold. This relies on the understanding of the functions and properties of the tissue microenvironment (TME), the specific extracellular environment within endogenous tissues. Although existing studies demonstrated the effect of each of the topographical, mechanical and biochemical properties on cell behaviors in isolation, the effect of these properties within the native TME are complicated and ill defined. This thesis aims to investigate how topographical, mechanical and biochemical features of natural TME contribute to the modulation of the biochemistry, morphology and functions of cells, and to translate this knowledge into the fabrication of biomaterials. Tissue cryosections as a cell culture model system was established. It allowed robust assessment of cell phenotypes in a near-natural TME. Mesenchymal stem cells (MSC) cultured on bone, cartilage and tendon cryosections adopted different morphology, supporting the idea that tissue cryosections forms a robust platform for cell-TME studies. Then, Achilles tendon TME was chosen for proof of concept. This tendon cryosection induced different cell types to adopt different morphologies, indicating that the effect of TME is cell type specific. The proliferation of MSC cultured on cryosection was suppressed, however it was instructed to commit tenogenic differentiation. Then, the necessity of TME topographical properties in forming this instruction was delineated by seeding MSC onto cross-sectional tendon cryosection. Although this surface contained native biomechanical and biochemical cues, it could not promote differentiation. This highlighted the necessity of topographical cues within the TME. Next, nano-grooved titanium surface that resembles the topographical cues of tendon TME was used to replicate the function of TME. This surface successfully promoted morphogenesis of MSC but not differentiation. This implicated that biomechanical and biochemical cues are both necessary for instructing desired cell phenotypes. The proteomes of MSC cultured on nanogrooved and planar surfaces were then studied using quantitative proteomics. This revealed some expected changes such as up regulation of cytoskeleton and cell-adhesion proteins, suggesting mechanotransduction events might have been induced by nano-grooved surface. However, expressions of RNA-binding proteins were also regulated, representing novel findings. These proteins were also found in the proteome of cellmicroenvironment interface identified through the use of subcellularfractionation and proteomics. This consolidated their involvement in cellmatrix interactions. The topographical and mechanical properties of cryosection were replicated by using bioimprinting. This imprint induced the morphogenesis of MSC, but tenocytic differentiation was induced only when collagen 1 was coated. However incorrect mechanical properties would abolish such phenotypic guidance. This suggests that topographical, mechanical and biochemical information in a TME are individually indispensable, and it is possible to functionally reconstruct a TME by bioimprinting and ECM protein coating. In summary, this study investigated the topographical, mechanical and biochemical properties in tendon TME and their combined effect on controlling cell phenotypes. It illustrates that biomimetic approach that mimics these three properties of a tissue can effectively control cell phenotypes. Further investigation on better biomimetic methods and its molecular mechanisms will help establishing strategies for constructing functional tissues. / published_or_final_version / Orthopaedics and Traumatology / Doctoral / Doctor of Philosophy