Mechanically sensitized hydrogel microspheres trigger membrane receptor switch for cartilage repair.

The development of cell scaffolds with unique mechanical properties and their interaction with stem cells will substantially advance stem cell bioengineering. In this study, mechanically sensitized microspheres with a self-prestressed mechanical structure were developed using oxidized bacterial nanocellulose (OBNC) as a scaffold. This study is the first to demonstrate that mechanical stress can trigger membrane receptor switch, enhancing the sensitivity of cells to the microenvironment and promoting interactions between stem cells and cell scaffolds for cartilage repair and regeneration. OBNC microspheres use local mechanical stress stimulation of stem cells through a self-stressing mechanical structure to trigger membrane receptor switch, thereby increasing the sensitivity of integrin receptors to the extracellular matrix (ligand). Moreover, OBNC microspheres can self-adapt to fill irregular cartilage injury sites and integrate cell scaffolds based on the strong adhesion of loaded stem cells following activation. Triggering of membrane receptor switch by nanoliposomes carrying OBNC scaffolds promotes the chondrogenic differentiation of stem cells, which repair and regenerate cartilage. In vitro and in vivo experiments revealed that the interaction between OBNC microspheres and stem cells effectively repaired cartilage damage caused by osteoarthritis. The results of this study provide new insights into the application of mechanical properties in stem cell bioengineering.