Mammalian Cell Interactions with Nanophase Materials

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Mammalian Cell Interactions with Nanophase Materials Rena Bizios Department of Biomedical Engineering and Rensselaer Nanotechnology Center, Rensselaer Polytechnic Institute, Troy, NY, 12180-3590, USA

ABSTRACT Adhesion of differentiated mammalian cells from various hard and soft tissues, including adult mesenchymal stem cells is different on nanophase than on microphase/conventional ceramics (such as alumina, titania and hydroxylapatite) as well as on composites of these ceramics with either poly(L-lactic) acid or poly(methyl) methacrylate. Most importantly, nanophase materials promote selective interactions, for example, of osteoblasts but not of fibroblasts. The type, amount and conformation of adsorbed proteins (such as fibronectin, collagen and vitronectin) are key aspects of the underlying mechanism(s) of subsequent cell interactions with nanophase materials. These cellular/molecular results provide evidence that nanophase biomaterials have the potential for improving the efficacy of implants and for promoting neotissue formation pertinent to tissue engineering, regenerative medicine and other clinical applications.

INTRODUCTION Current research on implantable biomaterials is motivated by the need for biomaterials with properties similar to those of the physiological tissues they are intended to replace. In addition there is the requirement that for the clinical success of implants, it is not enough to minimize undesirable tissue-biomaterial interactions. It is also necessary to promote specific functions of surrounding cells and tissues. In this respect, nanostructured materials (with grain sizes less than 100 nm in at least one dimension) are extremely promising. Supporting evidence has been provided by numerous, recent. in vitro studies, that utilized mammalian cells from various hard and soft tissues.

CELL ADHESION Among cell functions, adhesion is of primary and crucial importance for anchoragedependent cells because, when they do not adhere, those cells do not survive. Although cell proliferation can be expected to follow adhesion, proliferation (and other subsequent cell functions) need to be determined in separate and independent studies (specifically designed for that purpose) before definitive conclusions can be drawn. Understandably then, adhesion of mammalian cells to nanophase materials was the first function examined by researchers in this field. The first, statistically-significant

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evidence of enhanced adhesion of rat calvaria osteoblasts on flat, nanophase (versus microphase/conventional) ceramics (alumina, titania and hydroxylapatite) as a function of decreasing ceramic grain size was provided only a few years ago [1-2]. Most importantly, the enhanced adhesion was specific to osteoblasts, but neither to fibroblasts nor to endothelial cells [3]. Furthermore, the select preference and specific enhanced adhesion of osteoblasts was maintained only on composites of poly (L-lactic) acid (PLA) and nanophase (but not on polymer/conventional) ceramics (alumina, titania and hydroxyl