Osteoblast Response to Zirconia-Hybridized Pyrophosphate Stabilized Amorphous Calcium Phosphate

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dc.contributor.authorWhited, Bryce Matthewen
dc.contributor.committeechairLove, Brian J.en
dc.contributor.committeecochairGoldstein, Aaron S.en
dc.contributor.committeememberCotton, John R.en
dc.contributor.departmentBiomedical Engineeringen
dc.date.accessioned2014-03-14T20:36:37Zen
dc.date.adate2005-06-22en
dc.date.available2014-03-14T20:36:37Zen
dc.date.issued2005-05-04en
dc.date.rdate2007-06-22en
dc.date.sdate2005-05-13en
dc.description.abstractBiodegradable polyesters, such as poly(DL-lactic-co-glycolic acid) (PLGA), have been used to fabricate porous bone scaffolds to support bone tissue development. These scaffolds allow for cell seeding, attachment, growth and extracellular matrix production in vitro and are replaced by new bone tissue when implanted into bone sites in vivo. Hydroxyapatite (HAP) and μ-tricalcium phosphate (μ-TCP) ceramics have been incorporated into PLGA bone scaffolds and have been shown to increase their osteoconductivity (support cell attachment). Although HAP, μ-TCP, and biodegradable polyesters are osteoconductive, there is no evidence that these scaffold materials are osteoinductive (support cell differentiation). Calcium and phosphate ions, in contrast, have been postulated to be osteogenic factors that enhance osteoblast differentiation and mineralization. Recently, a zirconia-hybridized pyrophosphate stabilized amorphous calcium phosphate (Zr-ACP) has been synthesized which permits controlled release of calcium and phosphate ions and thus is hypothesized to be osteoinductive. Incorporation of Zr-ACP into a highly porous poly(DL lactic-co-glycolic acid) (PLGA) scaffold could potentially increase the osteoinductivity of the scaffold and therefore promote osteogenesis when implanted in vivo. To determine the osteoinductivity of Zr-ACP, a MC3T3-E1 mouse calvarial-derived osteoprogenitor cell line was used to measure cell response to Zr-ACP. To accomplish this objective, Zr-ACP was added to cell culture at different stages in cell maturation (days 0, 4 and 11). DNA synthesis, alkaline phosphatase (ALP) activity, osteopontin synthesis and collagen synthesis were determined. Results indicate that culture in the presence of Zr-ACP significantly increased cell proliferation, ALP activity and osteopontin synthesis but not collagen synthesis. To determine the feasibility of incorporating Zr-ACP into a PLGA scaffold, PLGA/Zr-ACP composite foams (5% or 10% (w/v) polymer:solvent with 25 wt% or 50 wt% Zr-ACP) were fabricated using a thermal phase inversion technique. Scanning electron microscopy revealed a highly porous structure with pores ranging in size from a few microns to about 100 μm. The amorphous structure of the Zr-ACP was maintained during composite fabrication as confirmed by X-ray diffraction measurements. Composite scaffolds also showed significantly greater compressive yield strengths and moduli as compared to pure polymer scaffolds. The results of this study indicate that Zr-ACP enhances the osteoblastic phenotype of MC3T3-E1 cells in vitro and can be incorporated into a porous PLGA scaffold. Porous PLGA/Zr-ACP composites are promising for use as bone scaffolds to heal bone defects.en
dc.description.degreeMaster of Scienceen
dc.identifier.otheretd-05132005-200348en
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-05132005-200348/en
dc.identifier.urihttp://hdl.handle.net/10919/32699en
dc.publisherVirginia Techen
dc.relation.haspartWhited_Thesis.pdfen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectosteogenesisen
dc.subjectdifferentiationen
dc.subjectosteoblasten
dc.subjectBone tissue engineeringen
dc.subjectpolylactic aciden
dc.subjectcalcium phosphateen
dc.titleOsteoblast Response to Zirconia-Hybridized Pyrophosphate Stabilized Amorphous Calcium Phosphateen
dc.typeThesisen
thesis.degree.disciplineBiomedical Engineeringen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.levelmastersen
thesis.degree.nameMaster of Scienceen

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