Stem Cell‐Recruiting Injectable Microgels for Repairing Osteoarthritis

Abstract The differentiation potentials and viability of stem cells are often impaired during cell isolation and delivery. Inspired by the phenomenon where islands can recruit seabirds for nesting, “cell island” microgels (MGs), that is, growth factor‐loaded methacrylated hyaluronic acid and heparin blend MGs, which can recruit endogenous stem cells and promote chondrogenic differentiation, are constructed using microfluidic technology and photopolymerization processes, followed by non‐covalently binding platelet‐derived growth factor‐BB (PDGF‐BB) and transforming growth factor‐beta3 (TGF‐β3). The loading efficiency of PDGF‐BB and TGF‐β3 are 96% and 91%, respectively. In vitro and in vivo experiments find that the “cell island” MGs can enhance the migratory capacity of cells and recruit them from their niche via releasing PDGF‐BB. Meanwhile, by using hyaluronic acid, the “cell island” MGs provide a suitable microenvironment for cell attachment and spreading. Furthermore, the “cell island” MGs induce chondrogenic differentiation of the recruited cells via releasing TGF‐β3 and present a promising therapeutic effect for osteoarthritis. In sum, this developed “cell island” MG might serve as a temporary “nest site” to allow the migration, adhesion, and differentiation of endogenous stem cells, which can be a promising candidate rather than the conventional cell‐seeded scaffolds for promoting tissue regeneration.