Injectable Microporous Annealed Particle Hydrogel Based on Guest-Host-Interlinked Polyethylene Glycol Maleimide...

Microporous annealed particle (MAP) hydrogels have emerged as a versatile biomaterial platform for regenerative medicine. MAP hydrogels have been used for the delivery of cells and organoids but often require annealing post injection by an external source. We engineered an injectable, self-annealing MAP hydrogel with reversible interparticle linkages based on guest-host functionalized polyethylene glycol maleimide (PEG-MAL) microgels. We evaluated the effect of guest-host linkages on different types of microgels fabricated by either batch emulsion or mechanical fragmentation methods. Batch emulsion generated small spherical microgels with controllable 10-100 μm diameters and mechanical fragmentation generated irregular microgels with larger diameters (100-200 μm). Spherical microgels (15 μm) showed self-healing behavior and completely recovered from high strain while fragmented microgels (133 μm) did not recover. Guest-host interactions significantly contributed to the mechanical properties of spherical microgels but had no effect on fragmented microgels. Spherical microgels were superior to the fragmented microgels for co-injection of immune cells and pancreatic islets due to their lower force of injection, demonstrating more homogeneously distributed cells and greater cell viability after injection. Based on these studies, the spherical guest-host MAP hydrogels provide a controllable, injectable scaffold for engineered microenvironments and cell delivery applications.