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Stem cell therapies have shown promising capabilities in regaining the functionality of scar tissue following a myocardial infarction. Biological sutures composed of fibrin have been shown to more effectively deliver human mesenchymal stem cells (hMSCs) to the heart when compared to traditional cell delivery mechanisms. While the biological sutures do show promise, improvements can be made. To enhance the fibrin sutures, we propose to incorporate native cardiac extracellular matrix (ECM) into the fibrin microthreads to produce a more in vivo-like environment. This project investigated the effects that ECM incorporation has on fibrin microthread structure, mechanics, stem cell seeding, and pro-angiogenic potential. Single microthreads composed of fibrin or fibrin and ECM were subjected to uniaxial tensile testing. It was found that the microthreads consisting of both fibrin and ECM had significantly high elastic moduli than fibrin only microthreads. Cell seeding potential was evaluated by performing a 24-hour hMSC seeding experiment using sutures of the varying microthread types. A CyQuant cell proliferation assay was used to determine the number of cells seeded onto each suture type. The results determined that there was no statistical difference between the numbers of cells seeded on the types of sutures. To examine the pro-angiogenic potential the microthreads had, a 24-hour endothelial progenitor outgrowth cell (EPOC) outgrowth assay was used. Fibrin and 15% ECM-fibrin microthreads were placed within the scratch of an EPOC culture and evaluated every 6 hours for 24 hours. We found that the 15% ECM microthreads had significantly increased the EPOC outgrowth, approximately 16% more distance travelled than fibrin microthreads and 18% more than no microthreads. Our combined results suggest that ECM does not affect hMSC attachment to biological sutures but does increase the pro-angiogenic potential of the microthreads due to their increase in guiding EPOC outgrowth.

published_or_final_version / Dentistry / Master / Master of Orthodontics

published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy

The basic principle of tissue engineering is the combination of appropriate cells with biomaterials under conditions that promote and lead to tissue formation. A tissue engineering scaffold is a material that supports cells for their growth, proliferation, and differentiation in the absence of native extracellular matrix (ECM). The ECM was originally thought to provide primarily a mechanical support for the cells, but through receptors on the surface of cells, the ECM takes part in promoting cell adhesion, migration, growth, differentiation, and apoptosis. Ideally, a tissue engineered scaffold should mimic both the form and function of native ECM. Additionally, like any other biomaterial for implantation, a tissue engineered scaffold should be biocompatible and not initiate tissue reactions or immune responses. This work focuses on the evaluation of the biocompatibility of novel alloy-based materials for orthopedic applications. In addition, in the context of bone regeneration, it examines the influence of select native ECM constituents on mesenchymal stem cell (MSC) osteogenic differentiation in 3-D contexts. On the other hand, given the crucial role of vasculogenesis in cell nutrition in the scaffolds, ECM mimics found to support osteogenesis were further evaluated for endothelial cell adhesion and migration. For the hydrogel systems presented in this manuscript, poly(ethylene glycol) diacrylate (PEGDA) networks were selected as the base scaffold due to the broad tunability of their mechanical properties and their previous use in bone regeneration applications. In addition, pure PEGDA hydrogels do not intrinsically promote cell adhesion. Thus, cell interactions with PEGDA gels are initially isolated to the interactions supported by the proteins tethered to the scaffold. This work attempts to contribute to the development of novel materials that provide biocompatibility and enhanced versatility in orthopedic applications. Moreover, in the context of bone regeneration, the use of selective ECM biomolecules in hybrid hydrogel scaffolds will aid in the understanding of MSC osteogenic responses to specific ECM constituents. Additionally, incorporation of ECM mimics that support both osteogenesis and vasculogenesis will provide a more controlled platform which will serve as a foundation for the fabrication of more efficient vascularized bone constructs.

Thesis (M. Phil.)--University of Hong Kong, 2008. / Also available in print.

Diss. (sammanfattning) Umeå : Univ., 2004. / Härtill 5 uppsatser.

Thesis (Ph. D.)--Ohio State University, 2008. / Title from first page of PDF file. Includes bibliographical references (p. 292-320).

Thesis (Ph. D.)--University of Hong Kong, 1998. / Includes bibliographical references (leaf 225-261).

Thesis (M.Orth.)--University of Hong Kong, 1999. / Includes bibliographical references (leaves 229-253). Also available in print.