Functional Hydrogels as Biomaterials by Jun Li & Yoshihito Osada & Justin Cooper-White

Author:Jun Li & Yoshihito Osada & Justin Cooper-White
Language: eng
Format: epub
ISBN: 9783662575116
Publisher: Springer Berlin Heidelberg

3.2.3 2D Versus 3D Environment

Although 2D cell culture offers a convenient platform to study stem cell behaviour and response to various physical, chemical or biological cues, it is far from being representative of the native 3D environment of the cells. Many parameters that have been shown to influence stem cell fate differ between a 2D and a 3D configuration, such as cell adhesion and morphology, the way cells sense the mechanical properties of the ECM and the transport of nutrients and gases [6].

Studies comparing the behaviour of hMSCs cultured in 2D and 3D have found that 3D conditions enhanced the differentiation potential of the cells [31]. It has been shown that the fate of hMSCs is influenced by the cell shape and cytoskeletal tension [57, 88, 134]. The way cells adhere to a 2D surface is different to attachment in a 3D environment, and by modifying the number and types of adhesions between the substrate and the cell, the morphology is likely to change, thus affecting the cell fate in terms of differentiation outcomes.

Similarly, the way cells move through a 3D environment is substantially different between a 2D and 3D environment. In 2D, cells are free to migrate and spread in any direction on the surface of the tissue culture plate. In 3D, cells need to remodel their physical environment or modify their shape in order to move through the pores of the network [136]. Again, these differences are likely to modify the cell/ECM interactions and therefore influence other fate choices, such as the differentiation outcome.

Central to many of these fate choices is the process of mechanotransduction [38], and this particular regulatory pathway is affected by the transition from a 2D to a 3D system: Huebsch et al. showed that the hMSC integrins involved in ECM interactions vary between a 2D and a 3D environment, which in turn can affect the way the cells sense and respond to the stiffness of the substrate [48]. For example, in opposition to the 2D situation, there was no correlation between the cell morphology and the cell fate, which indicates that other mechanotransduction mechanisms might be at play during the differentiation of stem cells in 3D.

Finally, when transitioning from a 2D to a 3D configuration, the diffusive parameters of the culture system are modified, which affects the transport of soluble factors, nutrients and gases [41]. Moreover, some ECM molecules can bind growth factors [87, 99] and slow down their progression. These two effects alter the diffusion of the nutrients and growth factors and generate local concentration gradients. Chemical gradients have been shown to have an effect on cell migration and differentiation, which in turn ensure the proper development of structured tissues both at the embryonic and adult stages [138]. Processes such as morphogenesis, wound healing, immune response, vascularisation, and axonal guidance are influenced by gradients [116]. Gradients in morphogens or chemokines can also be used to engineer interface tissues (e.g. from the cartilage to the bone) [109]. It is worth noting that physical gradients (e.

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