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

Abstract

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.

Multiparametric Material Functionality of Microtissue‐Based In Vitro Models as Alternatives to Animal Testing

“…This leads to a higher density of network strands per unit volume and thus to an increasing mechanical strength of PNIPAAm hydrogels with increasing temperature. [ 152 ] Möhwald and co‐workers for example have developed PNIPAAm microgel films for bioapplications, which show an increase of elastic modulus from 86 to 330 kPa with increasing temperature from 25.3 to 37.2 °C. [ 153 ] To further shift the VPTT of PNIPAAm and hence decrease or increase its mechanical strength at a given temperature (e.g., at physiological temperature) hydrophilic or hydrophobic comonomers can be incorporated into the PNIPAAm network.…”

“…Accordingly, PDA-coated PNIPAAmbased microgel templates were fabricated as in vitro models to allow for homogeneous and temperature-independent cell coating and adhesion on microgel surfaces to potentially mimic the blastula in embryogenesis, mammary glands, or alveolar epithelium. [152] Also, some types of PU materials enable protein adsorption due to hydrogen bonding between urethane groups and proteins as described by Sheikholeslam et al and Chernonosova et al [181,182] Both references included PU/gelatin composite materials for tissue engineering applications prepared by electrospinning, which showed good cell adhesion on these materials.…”

1H-NMR studies on the volume phase transition of DNA-modified pNipmam microgels

“…for biomedical applications. [1][2][3][4][5][6][7][8][9][10][11] In particular, the ability to undergo a temperature-induced collapse at a volume phase transition temperature (VPTT), which is determined by the lower critical solution temperature (LCST) of the constituting monomers, has been utilized so far in this respect. By reaching the VPTT, hydrogen bonds are disrupted which leads to a breakdown of the local water structure and allows the hydrophobic attractions to dominate.…”