Artificial Surfaces for Building Bone

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Science's STKE  03 May 2005:
Vol. 2005, Issue 282, pp. tw167
DOI: 10.1126/stke.2822005tw167

Suitable biomaterials that may serve as culture supports for generating bone and other tissues have important applications in treating various skeletal diseases and injuries. The surface chemistry of self-assembled monolayers (SAMs) alters the presentation of the integrin-binding domain of fibronectin (FN) adsorbed to the SAM. Keselowsky et al. determined how FN adsorbed onto SAMs with surface chemistries that were either hydrophobic (CH3), neutral hydrophilic (OH), negatively charged (COOH), or positively charged (NH2) affected osteoblast differentiation. Bone-specific gene expression was quantified by reverse transcription polymerase chain reaction (RT-PCR) from MC3T3-E1 murine immature osteoblasts plated onto the different FN-SAM surfaces. Markers associated with osteoblast differentiation were increased in cells plated on either the OH or NH2 surfaces but not the COOH or CH3 surfaces. Mineralization in scattered foci (called nodules) was also observed on the OH and NH2 surfaces, and this was enhanced compared with that observed on FN-coated polystyrene. The addition of antibodies that blocked integrin binding to human FN (used to create the FN-SAM coated surface) to the cultures blocked formation of matrix mineralization on the OH and NH2 surfaces. Addition of β1 or β3 function-blocking antibodies (to inhibit the major FN-binding integrins α5β1 and αvβ3) resulted in inhibition of matrix mineralization for the β1 antibody and increased mineralization for the β3 antibody on OH, NH2, and COOH surfaces. These results are consistent with the known effects of these different integrins on osteoblast differentiation. Thus, surfaces that promote bone formation can be bioengineered to maximize the interaction of bone-promoting integrins and minimize the binding of bone-inhibiting integrins.

B. G. Keselowsky, D. M. Collard, A. J. Garcia, Integrin binding specificity regulates biomaterial surface chemistry effects on cell differentiation. Proc. Natl. Acad. Sci. U.S.A. 102, 5953-5957 (2005). [Abstract] [Full Text]

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