Controllable microfluidic fabrication of monodisperse PCL microspheres for soft tissue augmentation

Monodisperse PCL microspheres with precise size regulation are fabricated via droplet-based microfluidics. • PCL microspheres exhibit superior long-term stability and excellent biocompatibility. • Monodisperse 42 μm PCL microspheres exhibit the most superior ability to stimulate collagen neogenesis. Polycaprolactone (PCL) microspheres are emerging as versatile biomaterials for minimally invasive soft tissue augmentation due to their tunable biodegradability and favorable biocompatibility. Nevertheless, the extent to which monodispersity governs the functional performance of PCL microspheres, particularly in modulating host tissue responses and regenerative efficacy, remains poorly understood. Herein, we propose a method to controllably prepare monodisperse oil-in-water (O/W) droplet templates using coaxial flow-focusing microfluidics, and then obtaining monodisperse PCL microspheres with programmable sizes via solvent evaporation. The droplet dimensions are inversely regulated by the outer-to-inner phase flow rate ratio, while PCL concentration in the organic phase exerts minimal influence on initial droplet size but markedly reduces the volume shrinkage during solidification, yielding microspheres that better retain their geometries. Notably, the resultant PCL microspheres can maintain structural integrity and size uniformity over two-month period under physiologically mimetic conditions. Comprehensive biocompatibility assessments reveal that PCL microspheres exhibit negligible hemolytic activity and cytotoxicity, demonstrating excellent hemocompatibility and cytocompatibility. Notably, in a rabbit soft tissue implantation model, monodisperse PCL microspheres with an average diameter of 42  μm elicit attenuated foreign body reactions and potentiate endogenous collagen deposition relative to the polydisperse microsphere control group. These results provide useful guidance for the application of PCL microspheres in soft tissue augmentation. Download: Download high-res image (210KB) Download: Download full-size image