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dc.rights.licenseCC BY-NC-ND. Users may download and share copies with attribution in accordance with a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License. No commercial use or derivatives are permitted without the explicit approval of the author.
dc.contributorCorr, David T.
dc.contributorChan, Deva
dc.contributorSun, Hui B.
dc.contributorWan, Leo Q.
dc.contributor.authorMubyana, Kuwabo
dc.date.accessioned2021-11-03T08:59:38Z
dc.date.available2021-11-03T08:59:38Z
dc.date.created2018-07-27T14:57:44Z
dc.date.issued2018-05
dc.identifier.urihttps://hdl.handle.net/20.500.13015/2179
dc.descriptionMay 2018
dc.descriptionSchool of Engineering
dc.description.abstractThe current standard for treatment of high grade tendon tears is surgical replacement grafts, however they present the challenge of limited tissue availability (allografts and autografts), donor site morbidity (autografts), and immune rejection (allografts and tissue engineered grafts). In recent years, several research groups have attempted to address this problem using scaffold-based tendon replacement grafts, and are faced with the challenge of developing a scaffold-based graft that (i) is biocompatible, (ii) emulates the properties of normal tendon tissue, and (iii) degrades at the ideal rate for successful tissue remodeling at the site of implantation, which if too soon, would lead to reinjury at the site, and if too late, would shield the endogenous tissue from the therapeutic benefits of gentle dynamic stretching and result in degeneration. Engineered scaffold-based tendon replacement grafts have yet to reach clinical implementation, and it is clear that a deeper understanding of how to enhance these grafts would help to advance these therapies and, potentially, improve the lives of patients.
dc.description.abstractThis thesis has provided unique insight on the roles of distinct mechanical stimuli and macromolecular crowding on tendon fiber development and maturation. The knowledge gained on cyclic uniaxial strain, quasi-static loading, and Ficoll-conditioning shows great promise for the advancement of tendon engineering strategies.
dc.description.abstractThe second aim examined the response of engineered, scaffold-free, dermal fibroblast-derived fibers to mechanical stimulation, namely cyclic uniaxial strain (designed to mimic motion-induced loading in the embryo), and quasi-static strain (to mimic limb lengthening-induced loading in the embryo). The results showed enhanced mechanical properties, collagen alignment, and collagen III deposition in the presence of loading and with loading duration. Moreover, cyclic strain increased stress-based properties (i.e., failure stress, Young’s modulus), but did not affect fiber extensibility. Conversely, the introduction of quasi-static strain increased fiber extensibility without affecting stress-based values. Taken together, these findings suggest distinctly different roles of cyclic and quasi-static strain in tendon development. In addition, the second aim assessed the response of a tendon-specific, progenitor cell type in this system, by using tendon stem/progenitor cells (TSPCs). There was limited success using TSPCs to engineer the tendon fibers. TSPC-derived fibers exhibited reduced extensibility after 34 hours in static culture and were too weak to be subjected to loading.
dc.description.abstractIn the first aim of my doctoral thesis, I developed a method to engineer individual scaffold-free tendon fibers using a micro-molded growth channel, which yielded higher throughput, greater consistency, and higher repeatability in the design of the growth channels than our laboratory’s previous technique for tendon fiber engineering. This micromold-based technique also enabled more extensive characterization of the response of engineered tendon fibers to mechanical and chemical cues.
dc.description.abstractPrimed with this knowledge, our laboratory has taken a more biomimetic approach to tendon tissue engineering—a scaffold-free approach that is inspired by key aspects of embryonic tendon development. By seeding a high density of cells into a growth channel without a provisional scaffold, and subjecting the cells to controlled mechanical and chemical cues, we are harnessing the cells’ innate ability to self-assemble, as seen in embryonic tenogenesis. It is a model of tissue regeneration rather than tissue remodeling.
dc.description.abstractThe final aim of this dissertation investigated the influence of macromolecular crowders on the mechanical properties of engineered scaffold-free tendon fibers. Two crowders, dextran sulfate (DsX) and Ficoll-cocktail, were tested. Fiber formation was unsuccessful in the presence of DsX. However, conditioning with Ficoll yielded significantly stronger, stiffer, and tougher fibers.
dc.language.isoENG
dc.publisherRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofRensselaer Theses and Dissertations Online Collection
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.subjectBiomedical engineering
dc.titleThe influence of mechanical stimulation and macromolecular crowding on engineered, scaffold-free tendon fibers
dc.typeElectronic thesis
dc.typeThesis
dc.digitool.pid178949
dc.digitool.pid178950
dc.digitool.pid178951
dc.rights.holderThis electronic version is a licensed copy owned by Rensselaer Polytechnic Institute, Troy, NY. Copyright of original work retained by author.
dc.description.degreePhD
dc.relation.departmentDept. of Biomedical Engineering


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CC BY-NC-ND. Users may download and share copies with attribution in accordance with a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License. No commercial use or derivatives are permitted without the explicit approval of the author.
Except where otherwise noted, this item's license is described as CC BY-NC-ND. Users may download and share copies with attribution in accordance with a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License. No commercial use or derivatives are permitted without the explicit approval of the author.