Mimicking the Graded Wavy Structure of the Anterior Cruciate Ligament.

Anterior cruciate ligament (ACL) is the connective tissue providing mechanical stability to the knee joint. ACL reconstruction upon rupture remains a clinical challenge due to the high mechanical properties required for proper functioning. ACL owes its outstanding mechanical properties to the arrangement of the ECM and to the cells with distinct phenotypes present along the length of the tissue. Tissue regeneration appears as an ideal alternative. In this study, we developed a tri-phasic fibrous scaffold that mimics the structure of collagen in the native ECM, presenting a wavy intermediate zone and two aligned uncurled extremes. The mechanical properties of the wavy scaffolds presented a toe region, characteristic of the native ACL, and an extended yield and ultimate strain as compared to traditional aligned scaffolds. The presentation of a wavy fiber arrangement affected the cell organization and the deposition of a specific ECM characteristic of fibrocartilage. Cells cultured in wavy scaffolds grew in aggregates, deposited an abundant ECM rich in fibronectin and collagen II, and expressed higher amounts of collagen II, X and tenomodulin as compared to aligned scaffolds. In-vivo implantation in rabbits showed a high cellular infiltration and the formation of an oriented ECM, as compared to traditional aligned scaffolds. This article is protected by copyright. All rights reserved.