Micromotion friction microspheres massage cells to promote interfacial tissue fusion and regeneration

Micromotion friction is a novel biomechanical stimulation approach that applies small mechanical forces to cells, mimicking the native biomechanical environment to enhance cellular physiological activity. Herein, combining microfluidic technology and photopolymerization, we report a micromotion friction site constructed by hydroxyapatite and doxycycline coupled to methacryloylated hyaluronic acid polyanionic hydrogel microspheres with a size of about 150 μm. The microspheres provided stable mechanical massage protection at the cell-tissue interfaces through electrostatic and steric repulsion interactions, enabling adjustable micromotion friction levels from the microscale to nanoscale. Our study demonstrated that microspheres can effectively stimulate cellular activity through micromotion friction to support interface tissue fusion and regeneration during anterior cruciate ligament reconstruction. In the early and middle stages, they actively provided microscale rolling lubrication (friction coefficient: 0.028-0.072) while slowly releasing anti-inflammatory factors to relieve inflammation. In the later stage, articular endogenous hyaluronidase triggers microsphere self-decomposition, transitioning to nanoscale hydration lubrication (friction coefficient: 0.027-0.078) and culminating in the complete release of tissue growth factors to enhance bone tunnel proliferation. In vivo studies demonstrated that microspheres induce extracellular matrix synthesis and micromotion friction functional factor secretion, thereby promoting interfacial tissue fusion and regeneration. Micromotion friction microspheres with actively massaging cells efficiently enhance cellular synthetic activity, suggesting a promising approach for tissue regeneration and highlighting a novel mechanical tool for regenerative medicine.