Rational Design of Thermoresponsive Microgel Templates with Polydopamine Surface Coating for Microtissue Applications

Functional microgels provide a versatile basis for synthetic in vitro platforms as alternatives to animal experiments. The tuning of the physical, chemical, and biological properties of synthetic microgels can be achieved by blending suitable polymers and formulating them such to reflect the heterogenous and complex nature of biological tissues. Based on this premise, this paper introduces the development of volume‐switchable core–shell microgels as 3D templates to enable cell growth for microtissue applications, using a systematic approach to tune the microgel properties based on a deep conceptual and practical understanding. Microscopic microgel design, such as the tailoring of the microgel size and spherical shape, is achieved by droplet‐based microfluidics, while on a nanoscopic scale, a thermoresponsive polymer basis, poly(N‐isopropylacrylamide) (PNIPAAm), is used to provide the microgel volume switchability. Since PNIPAAm has only limited cell‐growth promoting properties, the cell adhesion on the microgel is further improved by surface modification with polydopamine, which only slightly affects the microgel properties, thereby simplifying the system. To further tune the microgel thermoresponsiveness, different amounts of N‐hydroxyethylacrylamide are incorporated into the PNIPAAm network. In a final step, cell growth on the microgel surface is investigated, both at a single microgel platform and in spheroidal cell structures. Manufacturing of well‐designed core–shell templates, as a promising basis for complex and advanced 3D in vitro cell culture systems to replace, reduce, and refine animal testing. The microgels are tuned at nanoscopic, microscopic, and mesoscopic levels to obtain hydrogel scaffolds with functional and at the same time cell‐adhesive properties.