Enhancing cartilage repair in osteoarthritis via an injectable biomimetic synovial fluid incorporating of umbilical cord-derived mesenchymal stem cells

Osteoarthritis (OA) treatment currently lacks an effective integration of mechanical protection and biological repair. The present study aimed to design a stem cell delivery system that combines a biomimetic synovial fluid with human umbilical cord mesenchymal stem cells (Uc-MSCs) for the synergistic treatment of OA. Firstly, an injectable lubricant was prepared by the combination of polyacrylic acid amphiphilic ionomer (PG) and mussel adhesive protein (MAP). Uc-MSCs were incorporated into this matrix to form a biomimetic synovial fluid (Uc-MSCs@PG/MAP). The lubrication performance, antioxidant capacity, and cytocompatibility of Uc-MSCs@PG/MAP were assessed, revealing excellent lubrication, reactive oxygen species (ROS) scavenging ability, and the capacity to maintain stem cell viability. The as-developed synovial fluid not only enhances joint lubrication but also functions as a carrier for the delivery of umbilical cord - derived mesenchymal stem cells. In vivo experimental results indicate that it reduces early-stage stress through hydrodynamic lubrication and promotes late-stage cartilage regeneration via stem cell differentiation and paracrine signaling. This combined approach significantly outperforms monotherapies by inhibiting matrix metalloproteinase-13 (MMP-13) and pro-inflammatory cytokines (TNF-αand IL-6). This strategy successfully integrates “mechanical lubrication” with “biological regeneration,” presenting a highly translatable and minimally invasive solution for the management of OA.