The pace of progress in tissue engineering and biomedical research could be accelerated by developing improved biofabrication methods that are capable of precisely assembling cells into complex structures. Embedded 3D bioprinting, which often uses packed microgel particles as a support environment, is a promising way to manufacture and culture tissue constructs. The facile reconfigurability of noncohesive microgel support materials enables precise printing but possesses limited mechanical stability. By contrast, cohesive microgels provide enhanced stability yet create kinetic or energetic constraints to reconfiguration during embedded 3D printing processes. Here, we introduce a microgel system that combines the benefits of both cohesive and noncohesive microgels by grafting a poly(N-isopropylacrylamide) (PNIPAM) shell onto polyethylene glycol (PEG) microgel core. These PNIPAM-coated PEG microgels exhibit temperature-dependent interparticle interactions. At room temperature, the microgels remain noncohesive, minimizing constraints on particle reconfiguration and enabling high-quality biofabrication. Upon incubation at 37 °C, the microgels transition to a cohesive state, providing additional structural integrity during tissue culture. We find a phase partitioning behavior between PNIPAM polymer chains and bare PEG microgels that underpins the surface grafting process and correlates with a unique transition in its yielding behavior that is not exhibited by bare PEG microgels. Additionally, the PEG/PNIPAM microgels exhibit only weakly varying linear material properties across temperature shifts, in contrast to pure PEG microgels, which soften dramatically at higher temperatures. Tests of 3D bioprinting structures made from MDCK and 3t3 cells demonstrate the PNIPAM-coated PEG microgel system's ability to maintain cell viability and structure during tissue culture. The work reported here highlights the potential of this thermally tunable microgel system for use in advanced tissue engineering applications, offering precision during fabrication and stability during tissue culture.
Duraivel et al. (Sat,) studied this question.