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METHODS TO QUANTITATIVELY ASSESS THE PERFORMANCE OF CONNECTIVE TISSUE PROGENITOR CELLS IN RESPONSE TO SURFACE MODIFIED BIOMATERIALS

Raut, Vivek P

Abstract Details

2013, Doctor of Philosophy, Case Western Reserve University, Biomedical Engineering.
The field of orthopaedic tissue engineering includes a broad range of treatment options that seek to regenerate or accelerate the repair of bone tissue. Formation of new bone by the activity of connective tissue progenitor cells (CTPs) is a central feature of each of these treatment options. CTPs are defined as the heterogeneous population of stem and progenitor cells that are resident in native tissues and are capable of proliferation to give rise to progeny that will differentiate to express one or more connective tissue phenotypes. The strategy of using a cell-based therapy to achieve bone regeneration may include: targeting CTPs, and guiding their downstream progression towards the osteogenic pathway using a combination of scaffolds, bioactive factors, and mechanical and biophysical methods. Recent advancements in biomaterials science include promising technologies for modifying biomaterial surfaces with pro-survival or pro-osteogenic bioactive ligands. Before testing the pre-clinical efficacy of these surface modified biomaterials in animal models, it is important to test and optimize the influence of these materials on cells in an in vitro setting. The purpose of this dissertation is to introduce and demonstrate a new method to assess the response of CTPs to surface-modified biomaterials using a standardized automated colony forming unit (CFU) assay. Individual components of the method are verified for their compliance with the technical specifications. The method is validated using ß-TriCalcium Phosphate (TCP), a bone scaffold material that was modified with Epidermal Growth Factor (EGF), a pro-survival and proliferation bioactive ligand, using a novel TCP-binding peptide. The amount of tethered EGF on the TCP surface was quantified, and its stability was demonstrated. Surfaces modified with tethered EGF were shown to enhance the colony forming efficiency of CTPs obtained from human bone marrow and the trabecular surface of bone. These data support the potential of tethered EGF presentation on the surface of implantable TCP biomaterials as a means of enhancing the performance of local and transplanted CTPs in a setting of bone repair or other tissue engineering applications.
George Muschler, MD (Advisor)
159 p.

Recommended Citations

Citations

  • Raut, V. P. (2013). METHODS TO QUANTITATIVELY ASSESS THE PERFORMANCE OF CONNECTIVE TISSUE PROGENITOR CELLS IN RESPONSE TO SURFACE MODIFIED BIOMATERIALS [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1372334668

    APA Style (7th edition)

  • Raut, Vivek. METHODS TO QUANTITATIVELY ASSESS THE PERFORMANCE OF CONNECTIVE TISSUE PROGENITOR CELLS IN RESPONSE TO SURFACE MODIFIED BIOMATERIALS. 2013. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1372334668.

    MLA Style (8th edition)

  • Raut, Vivek. "METHODS TO QUANTITATIVELY ASSESS THE PERFORMANCE OF CONNECTIVE TISSUE PROGENITOR CELLS IN RESPONSE TO SURFACE MODIFIED BIOMATERIALS." Doctoral dissertation, Case Western Reserve University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=case1372334668

    Chicago Manual of Style (17th edition)