Self-Healing Zwitterionic Microgels as a Versatile Platform for Malleable Cell Constructs and Injectable Therapies

Injectable and malleable hydrogels that combine excellent biocompatibility, physiological stability, and ease of use are highly desirable for biomedical applications. Here, a simple and scalable strategy is reported to make injectable and malleable zwitterionic polycarboxybetaine hydrogels, which are superhydrophilic, nonimmunogenic, and completely devoid of nonspecific interactions. When zwitterionic microgels are reconstructed, the combination of covalent crosslinking inside each microgel and supramolecular interactions between them gives the resulting zwitterionic injectable pellet (ZIP) constructs supportive moduli and tunable viscoelasticity. ZIP constructs can be lyophilized to a sterile powder that fully recovers its strength and elasticity upon rehydration, simplifying storage and formulation. The lyophilized powder can be reconstituted with any aqueous suspension of cells or therapeutics, and rapidly and spontaneously self-heals into a homogeneous composite construct. This versatile and highly biocompatible platform material shows great promise for many applications, including as an injectable cell culture scaffold that promotes multipotent stem cell expansion and provides oxidative stress protection.