Instructive hydrogels with a physicochemical response

In general, naturally occurring polymers do not exhibit thermal responsiveness. Various strategies were envisioned to confer this physicochemical property to polysaccharides, such as chemical modification or formation of interpenetrated networks with other thermoresponsive polymers. Most of the published works report the use of thermoresponsive hydrogels based on PNlPAAm (Rzaev et a/., 2007). Examples of copolymers which may be grafted with PN IPAAm are chitosan (Martins e/ /., 2011), de xtran (Huang and Lowe, 2005 Huh et al, 2000), gelatin (Ohya and Matsuda, 2005), or 

2 Examples of triggered cross-linked hydrogels. (a)Temperature, pH, and light-triggered sol-gel transition, (b) Polymeric chains with grafted antibodies are cross-linked in the presence of specific antigens, (c) Polymeric chains with immobilized RGD are cross-linked in the presence of cells. 

A different candidate is Pluronic, an amphiphilic triblock copolymer of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), (PEO-PPO-PEO) (Frisman et al., 2011a,b Fusco et al., 2006 Ni et al., 2009 Shachaf et a/., 2010 ). 

The fabrication of engineered hydrogels that mimic the invasive characteristics of native provisional extracellular matrices with controllable degradation rate holds great promise in the development of new smart instructive materials (Hu et al., 2012 HubbeU, 1999 Lutolf et al., 2003b). It is important to note that the control of 3D cell migration within a biomaterial plays a critical role in TE (Ulijn et al., 2007). Insufficient cell migration in a scaffold is a major limitation in the formation of complex TE constructs. Thus, the 

In a different strategy, light was used to control hydrogel degradation in well-defined patterns. 

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