Advisory Committee Chair
Ho-Wook Jun
Advisory Committee Members
Susan L Bellis
Renato P Camata
Thomas L Clemens
Timothy M Wick
Document Type
Thesis
Date of Award
2008
Degree Name by School
Master of Science in Biomedical Engineering (MSBME) School of Engineering
Abstract
Bone is a dense, connective tissue with an extracellular matrix (ECM) comprised of biological and organic/inorganic biphasic matrices. For this study, novel peptide amphiphile (PA) nanomatrices were synthesized to mimic the native bone ECM and evaluated with human mesenchymal stem cells (hMSCs) isolated from bone marrow. The ability of this nanoscale, biomimetic scaffold composed of PAs that are inscribed with cellular adhesive ligands to direct hMSC osteogenic differentiation without supplements, along with other cellular behaviors, was investigated. Typical osteogenic supplements include dexamethasone, β-glycerol phosphate, and ascorbic acid. The synthesized PA sequences were evaluated as two-dimensional nanomatrix coatings without the inorganic component. In the 2-D nanomatrix environment, it was hypothesized that the PA nanomatrix could induce osteogenic differentiation of hMSCs without the presence of soluble factors based only on the incorporated cell adhesive ligands. Three different ligand peptide sequences (i.e. RGDS, DGEA, KRSR) that promote either integrin- or non-integrin-mediated cell binding were isolated and functionalized within the PA nanomatrices. hMSCs were seeded on the designed PA nanomatrices to assess the influence of each ligand signal on cellular behaviors. Initial attachment results demonstrated the adhesive ligands within the nanomatrices could be individually recognized and invoke different cellular responses. Long-term studies assessed osteogenic differentiation. Analysis of alkaline phosphate and osteopontin iv secretion, markers for osteogenic differentiation, found the RGDS-containing nanomatrix to be the most promising. Evaluations of hMSC morphology and mineral deposition provided further support. Overall, the results clearly suggested that the PA nanomatrix directs osteogenic differentiation without the aid of supplements by mimicking the native ECM, providing an adaptable environment that allows for different adhesive ligands and types of cell-mediated binding to influence cellular behaviors. This is a promising discovery that allows for future experiments to further explore osteogenic differentiation driven by ligand signaling within the PA nanomatrix, along with eventually incorporating the inorganic components. Altogether, this research model establishes the beginnings of a new versatile approach to regenerate bone tissues, along with a variety of other tissues, by closely following the principles of natural tissue formation.
Recommended Citation
Anderson, Joel M., "Biomimetic Self -Assembled Nanomatrix For Bone Tissue Regeneration" (2008). All ETDs from UAB. 3551.
https://digitalcommons.library.uab.edu/etd-collection/3551