Advanced Injectable Microgels: Porous, Small-Sized, and Lubricated Systems for Targeted Synergistic Therapy in Osteoarthritis

Microgels have attracted increasing attention as drug carriers for osteoarthritis (OA) treatment due to their injectability and modifiability. However, effectively designing high-efficiency drug-loading and multifunctional microgel carriers to achieve synergistic therapy of OA remains a challenge. Here, monodisperse, small-sized, porous, lubricated microgels composed of hyaluronic acid and polysulfomethylacrylate are developed using a multiple Pickering emulsion process. Then, the surface of microgels is modified with the cartilage-targeting peptide screened through phage display technology to create targeted microgels. The microgels exhibit porosity, small size (≈20 µm) and a swelling ratio of up to 4136.67%, which facilitate efficient loading, targeted delivery, and controlled release of miR-140, maintaining the metabolic balance of cartilage matrix and inhibiting the development of OA. Additionally, the microgels demonstrate remarkable lubrication performance attributed to the formation of the hydration layer around the hydrophilic groups of the polymers. The in vivo data demonstrate synergistic lubrication and sustained targeted release of miR-140 by the microgels, resulting in reduced joint wear, decreased osteophyte formation, and effective alleviation of OA progression. This work not only offers a novel method for the preparation of multifunctional microgels, but also lays the foundation for providing new strategies and clinical translation in OA the treatment.