Scull Grant, Thompson Jacob D, Osareh Melika, Rey Ysabel, Aligwekwe Adrian, Finkelstein Sofie, Schnabel Lauren V, Fisher Matthew B, Brown Ashley
Lampe Joint Department of Biomedical Engineering, North Carolina State University & University of North Carolina at Chapel Hill, Raleigh, North Carolina, USA.
Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina, USA.
J Biomed Mater Res A. 2025 Apr;113(4):e37901. doi: 10.1002/jbm.a.37901.
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.
膝关节肌肉骨骼损伤很常见且使人虚弱，最常见的软组织损伤是前交叉韧带（ACL）撕裂和半月板撕裂。这些撕裂伤自然愈合情况不佳，涉及支架的生物疗法往往也不成功，部分原因是关节的滑液环境。粘性滑液含有高浓度的降解酶，包括纤溶酶，这会阻止临时纤维蛋白支架的稳定形成。缺乏临时支架的形成会阻碍撕裂组织的桥接以及随后为实现永久性组织修复而进行的重塑。可以将凝血因子（如纤维蛋白原和凝血酶）与合成血小板样颗粒（PLP）结合后引入滑液中，以促进纤维蛋白支架的形成。PLP与纤维蛋白纤维结合并使其收缩，以增强纤维蛋白支架的硬度、密度和稳定性。因此，本研究的目的是探究PLP在增强滑液中纤维蛋白支架形成和降解能力方面的作用，并对所得支架的结构、密度和力学性能进行表征。我们研究了高粘度或低粘度滑液中的效果，因为粘度会随损伤而变化，且个体之间也存在差异。在向滑液中添加凝血因子和PLP后，我们发现低粘度滑液组的纤维蛋白支架密度、结构和最大力学性能有所增加，但高粘度滑液组没有。此外，通过用透明质酸酶降低滑液粘度，添加PLP后支架密度的增加得以恢复，这表明滑液粘度对稳定支架形成具有重要作用。这项技术有助于开发一种更有效的用于关节内肌肉骨骼损伤的基于纤维蛋白的治疗方法。
