Sustained and controllable local gene therapy is a potential method for treating osteoarthritis (OA). Here, monodisperse gelatin methacryloyl microspheres produced under one-step innovative microfluidic technology were applied to construct “nano-micron” combined gene hydrogel by absorbing gene nanoparticles consisting of microRNA-140 and multifunctional gene vectors, arginine, histidine, and phenylalanine-modified generation 5 polyamidoamine (named G5-AHP). The “nano-micron” combined gene hydrogel showed better injectability in sustainable and matrix metalloproteinases-responsive degradation methods and provided a novel cell-free approach to alleviate the progression of OA.
