In this proposal, we will investigate a potential new way of bone healing. It is widely known that implant materials have been used for many years to support tissue repair or regeneration. It is now thought that such implants may also induce natural bone healing responses by living tissues and cells. Specifically, bioactive glasses have shown this ability to induce osteoblast response for bone healing by releasing bioactive glass ions. The purpose of this proposed work is to explore this novel idea that bioactive glass ions play an active role in bone healing and bone regeneration. To investigate the influence of these ions on bone healing, we will examine how these glasses interact with cells from an intracellular and extracellular perspective. First, it is believed that bioactive glass ions, which are release by glasses during immersion in physiological fluid, may induce various responses by osteoblasts. Second, these bioactive glass ions (namely silicon and calcium) may combinatorially control osteoblast function such that bone regeneration is hastened or enhanced. Finally, we investigate how bioactive glasses ion release can be controlled using a programmed bioactive glass. The techniques used to determine the influence of bioactive glass ions on gene expression and extracellular activity includes gene microarrays, real time polymer chain reaction, immunoassays, and immunohistochemistry. To program bioactive glasses, chemical vapor deposition is used to build nanolayered and microlayered composite glasses that deliver target ion concentrations to cells for enhanced osteoblast function.
The aims and goals of this proposed work fit into the mission of NIH, that is, improving biomaterials by improving our understanding of cell-biomaterial interactions and exploring new methods in fabricating """"""""smart"""""""" biomaterials. The work proposed here investigates biomedical device-cell interactions for bone healing. Specifically, we wish to control and improve bone healing through controlled biomaterial degradation in physiological fluid. The proposed work is aimed at developing materials that are self-regulating for gene-related therapies. Therefore, improving our understanding of tissue-biomedical device interactions can lead to devices that improve tissue healing and ease patient suffering owed to debilitating conditions and diseased.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Mentored Quantitative Research Career Development Award (K25)
Project #
5K25DE018230-03
Application #
7630506
Study Section
Special Emphasis Panel (ZDE1-RK (06))
Program Officer
Hardwick, Kevin S
Project Start
2007-08-01
Project End
2012-06-30
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
3
Fiscal Year
2009
Total Cost
$121,770
Indirect Cost
Name
University of California San Francisco
Department
Dentistry
Type
Schools of Dentistry
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Nar, Mangesh; Staufenberg, Gerrit; Yang, Bing et al. (2014) Osteoconductive bio-based meshes based on poly(hydroxybutyrate-co-hydroxyvalerate) and poly(butylene adipate-co-terephthalate) blends. Mater Sci Eng C Mater Biol Appl 38:315-24
Saffarian Tousi, Neda; Velten, Megen F; Bishop, Timothy J et al. (2013) Combinatorial effect of Si4+, Ca2+, and Mg2+ released from bioactive glasses on osteoblast osteocalcin expression and biomineralization. Mater Sci Eng C Mater Biol Appl 33:2757-65
Varanasi, Venu G; Leong, Kelly K; Dominia, Lisa M et al. (2012) Si and Ca individually and combinatorially target enhanced MC3T3-E1 subclone 4 early osteogenic marker expression. J Oral Implantol 38:325-36
Varanasi, Venu G; Owyoung, Jeremy B; Saiz, Eduardo et al. (2011) The ionic products of bioactive glass particle dissolution enhance periodontal ligament fibroblast osteocalcin expression and enhance early mineralized tissue development. J Biomed Mater Res A 98:177-84
Varanasi, V G; Saiz, E; Loomer, P M et al. (2009) Enhanced osteocalcin expression by osteoblast-like cells (MC3T3-E1) exposed to bioactive coating glass (SiO2-CaO-P2O5-MgO-K2O-Na2O system) ions. Acta Biomater 5:3536-47