State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Laboratory of Advanced Materials, Fudan University, Shanghai, 200433, PR China.
Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, PR China.
Acta Biomater. 2020 Apr 1;106:102-113. doi: 10.1016/j.actbio.2020.01.045. Epub 2020 Feb 1.
With developments in tissue engineering, artificial ligaments are expected to be future materials for anterior cruciate ligament (ACL) reconstruction. However, poor healing of the intraosseous part after ACL reconstruction significantly hinders their applications in this field. In this study, a bioactive clay Laponite (LAP) was introduced into the regenerated silk fibroin (RSF) spinning dope to produce functional RSF/LAP hybrid fibers by wet-spinning. These RSF/LAP hybrid fibers were then woven into artificial ligament for ACL reconstruction. The structure and mechanical properties of RSF/LAP hybrid fibers were extensively studied by different means. Results confirmed the presence of LAP in RSF fibers and revealed that the addition of LAP slightly deteriorated the comprehensive mechanical properties of RSF fibers. However, they were still much tougher (with higher breaking energy) than those of degummed natural silkworm silk that was earlier used for making artificial ligament. The artificial ligament woven from RSF/LAP hybrid fibers showed better cytocompatibility and osteogenic differentiation with mouse pre-osteoblasts in vitro than those made from degummed natural silkworm silks and pure RSF fibers. Furthermore, in vivo study in a rat ACL reconstruction model demonstrated that the presence of LAP in the artificial ligament could significantly enhance the graft osseointegration process and also improve the corresponding biomechanical properties of the artificial ligament. Based upon these results, the RSF/LAP hybrid fibers, which can be mass produced by wet-spinning process, are believed to have a great potential for use as artificial ligament materials for ACL reconstruction. STATEMENT OF SIGNIFICANCE: In this study, we successfully introduced Laponite (LAP), a kind of clay that has the function of osteogenic induction, into regenerated silk fibroin (RSF) fibers, which was prepared by a mature wet-spinning method developed in our lab. We believe that through artificial spinning, additional functional components can be added into RSF fibers, which one can hardly achieve with natural silks. We showed that the artificial ligament woven from RSF/LAP hybrid fibers had better cytocompatibility and osteogenic differentiation for mouse pre-osteoblasts in vitro, and significantly enhanced the graft osseointegration process and improved the corresponding biomechanical properties in a rat ACL reconstruction model in vivo, compared to those artificial ligaments made from degummed natural silkworm silks and pure RSF fibers.
随着组织工程学的发展,人工韧带有望成为前交叉韧带(ACL)重建的未来材料。然而,ACL 重建后骨内部分的愈合不良严重阻碍了它们在该领域的应用。在这项研究中,将具有生物活性的粘土 Laponite(LAP)引入再生丝素(RSF)纺丝溶液中,通过湿法纺丝制备功能性 RSF/LAP 杂化纤维。然后将这些 RSF/LAP 杂化纤维编织成用于 ACL 重建的人工韧带。通过不同的方法广泛研究了 RSF/LAP 杂化纤维的结构和力学性能。结果证实了 LAP 存在于 RSF 纤维中,并表明添加 LAP 略微降低了 RSF 纤维的综合力学性能。然而,与以前用于制造人工韧带的脱胶天然桑蚕丝相比,它们仍然更加坚韧(具有更高的断裂能)。由 RSF/LAP 杂化纤维编织而成的人工韧带在体外与小鼠成骨前体细胞的细胞相容性和成骨分化性优于由脱胶天然桑蚕丝和纯 RSF 纤维制成的人工韧带。此外,在大鼠 ACL 重建模型中的体内研究表明,人工韧带中存在 LAP 可以显著增强移植物的骨整合过程,并改善人工韧带的相应生物力学性能。基于这些结果,我们相信,通过湿法纺丝工艺可以大规模生产的 RSF/LAP 杂化纤维,具有作为 ACL 重建人工韧带材料的巨大潜力。 意义声明:在这项研究中,我们成功地将具有成骨诱导功能的粘土 Laponite(LAP)引入到由我们实验室开发的成熟湿法纺丝方法制备的再生丝素(RSF)纤维中。我们相信,通过人工纺丝,可以向 RSF 纤维中添加额外的功能成分,而这在天然丝中很难实现。我们发现,与由脱胶天然桑蚕丝和纯 RSF 纤维制成的人工韧带相比,由 RSF/LAP 杂化纤维编织而成的人工韧带具有更好的体外细胞相容性和成骨分化能力,并且在大鼠 ACL 重建模型的体内研究中,明显增强了移植物的骨整合过程,并改善了相应的生物力学性能。