Noninvasive Fibrin Targeting Colloid-Mediated Intra-Articular Repair

Abstract

Musculoskeletal knee injuries are common and debilitating, with the most prevalent soft tissue injuries being anterior cruciate ligament (ACL) and meniscal tears. These tears do not heal well naturally, and biological therapies involving scaffolds are often unsuccessful, due in part to the synovial fluid environment of the joint. Viscous synovial fluid contains high concentrations of degradative enzymes, including plasmin, which prevents the stable formation of provisional fibrin scaffolds. Lack of provisional scaffold formation prevents bridging of torn tissue and subsequent remodeling for permanent tissue repair. Coagulation factors such as fibrinogen and thrombin, reinforced with synthetic platelet-like particles (PLPs), can be introduced to synovial fluid to promote fibrin scaffold formation. PLPs bind to and retract fibrin fibers to enhance stiffness, density, and stability of fibrin scaffolds. Therefore, the objective of this work is to investigate the role of PLPs in enhancing fibrin scaffold formation and degradation capabilities within synovial fluid and to characterize the resulting scaffold structure, density, and mechanics. We investigated effects in synovial fluid with high or low viscosity, as viscosity can change with injury and can vary between individuals. Following the addition of clotting factors and PLPs to synovial fluid, we found an increase in fibrin scaffold density, structure, and maximum mechanics for low viscosity, but not high viscosity, synovial fluid groups. Furthermore, by lowering the viscosity of synovial fluid with hyaluronidase, the increase in scaffold density following PLP addition was restored, indicating the strong role of synovial fluid viscosity on stable scaffold formation. This technology contributes to the development of a more robust fibrin-based therapy for intra-articular musculoskeletal injuries.