Engineering 3 D cell-culture matrices : multiphoton processing technologies for biological and tissue engineering applications

www.expert-reviews.com ISSN 1743-4440 © 2012 Expert Reviews Ltd 10.1586/ERD.12.48 Conventional cell-culture systems used in biology do not accurately reproduce the structure, function or physiology of living tissue [1]. As a result, there are substantial discrepancies in behavior and responses of cells compared with in vivo environments. For example, Bokhari et al. have shown that HepG2 hepatocytes grown on 3D polystyrene scaffolds are less susceptible to certain toxicological challenges [2]. Their work suggested that testing drugs on liver cells should be performed in a 3D cell culture, since observed responses are more similar to that of natural tissue. Stegemann et al. have shown that the response of vascular smooth muscle cells (VSMCs) to the biochemical and mechanical signals differs depending on the extracellular environment [3]. The evaluation of interplay between different biomimetic factors is particularly challenging. For example, MJ Bissel’s group has shown that both appropriate matrix elasticity and presence of laminin are required in order for mammary epithelial cells to maintain their differentiated phenotype [4]. Similarly, Peyton et al. revealed a synergetic effect of matrix elasticity and RhoA activation on the VSMC phenotype [5]. Numerous other examples can be found in related reviews on this topic [6–8]. Until recently, cell-culture matrices were mainly considered from a standpoint of support and guidance of cell proliferation and tissue development. The early designs of tissue engineering constructs focused on bulk properties, while disregarding the individual cell environment. A number of approaches for the realization of porous matrices, in the form of hydrogels or scaffolds, have been developed in recent years; with a different degree of success they all aim at approximating the complexity of the natural cell environment. However, the majority of current methods for realization of 3D cell-culture matrices allow the study of only particular biomimetic aspects of a natural extracellular matrix (ECM) without the possibility to evaluate the interplay of different effects. The main reason for this is that, owing to the technical limitations of these Aleksandr Ovsianikov*1, Vladimir Mironov2, Jürgen Stampfl1 and Robert Liska1