University of Wisconsin System
Grant: $450,000 - National Science Foundation - Jun. 5, 2009
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Award Description: INTELLECTUAL MERIT: The chemical composition of bioactive silicate bioceramics or glasses & the leached Si&Ca concentrations strongly influence the complex process of osteointegration by affecting the texture of the amorphous silica&carbonated hydroxyapatite(Ca5(PO4)3OH, HCA)layers formed at the implant surface, the adsorption of proteins,&human mesenchymal stem cell(hMSC)attachment, proliferation&differentiation into osteoblasts that produce new bone. Distinct from ion concentrations, the effect of ion release rates on cellular activity,&the critical control exerted by silicate structure&dissolution mechanisms on ion release rates&overall concentrations,&on resulting surface texture has not been examined previously. The PIs hypothesize that, for surfaces of similar initial texture, silicate structure exerts a major control on the dissolution mechanism, affecting the concentration&rate of ions released, the texture of the precipitated amorphous silica&HCA layers, the activation of specific genes and, ultimately, hMSC proliferation&differentiation into osteoblasts. This hypothesis will be tested by performing batch&flow-through experiments&determining hMSC proliferation&differentiation on pseudowollastonite (beta-CaSiO3, psW)&wollastonite (alpha- CaSiO3, Wol). The psW polymorph possesses strained high-energy silicate three-rings that dissolve rapidly in water versus the stronger silicate chains in Wol that dissolve slower, while Bioglass 45S5 provides a positive control. Silicate structure&initial surface texture (roughness&particle size) effects will be examined independently. The dissolution&precipitation mechanisms&rates will be established by periodic solution analysis (pH, Si, Ca, P) using Inductively-Coupled Plasma Optical Emission Spectroscopy&by surface characterization using Scanning Electron Microscopy with Energy-Dispersive X-Ray Spectroscopy&High Resolution Transmission Electron Microscopy. Reacted pellets will be used as substrates for hMSC cultures in standard culture media supplemented with osteogenic differentiation factors. Proliferation&differentiation into osteoblasts will be quantified periodically by fluorescence&total DNA content, osteocalcin&alkaline phosphatase analyses (enzymes produced by osteoblasts),&identification of bone-specific genes (Cbfa-1, osteocalcin, osteopontin) using real time polymerase chain reaction. Periodic culture medium sampling will provide information on ion release rates in the presence of cells. The conceptual approach&experimental design provides a comprehensive group of ex vivo experiments that are closer to in vivo conditions than typical in vitro batch experiments in simulated body fluids, while examination of the effects of each parameter separately. BROADER IMPACTS: The results of the proposed work could have a significant impact on the development of third-generation cell-and gene-affecting bioceramics with improved osteointegration properties, by providing an a priori basis for designing bioactive materials that control Si, Ca&P levels at optimized levels for hMSC proliferation, differentiation&osteoblast activity. The results could thus help to reduce dependence on expensive ad hoc materials synthesis&in vitro testing, decrease the post-operative recovery period following orthopaedic implant surgery&increase the life-span of the implant in the human body. The biomedical implications are especially critical for an increasingly aging population in the USA, where a significant rise (~80%) is projected in the demand for hip&knee implant surgeries over the next three decades. The proposed work also provides an integrated, interdisciplinary training program including surface-chemistry, crystal structure&cell biology to graduate&undergraduate students. Results will be disseminated in peer-reviewed journals&at conferences; incorporated into graduate courses taught by the PI&co-PI;&used to develop a Museum Exhibit for K-12 students at University of Wisconsin.
Project Description: See Award Description
Jobs Summary: The University of Wisconsin - Madison appreciates the American Recovery and Reinvestment Act (ARRA) funding. This additional funding has allowed us to retain employees and create new jobs. The job classifications that have been created or retained for this award are: Research Support positions. (Total jobs reported: 1)
Project Status: Not Started
This award's data was last updated on Jun. 5, 2009. Help expand these official descriptions using the wiki below.
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