Tissue Engineering of the Anterior Cruciate Ligament on Resorbable Embroidered Scaffolds: Design of a Hybrid Scaffold Structure Composed of a Biomechanical Unit , a Bio-Functional Unit and a Vital Unit

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The replacement of the anterior cruciate ligament (ACL) by a tissue engineering approach could be the favored surgical practice in future superseding the transplantation of autologous tendons with limited availability. An essential requirement for the application is a sufficient biomechanical resistance of the surrogate structure. The proposed project focusses on the design of a hybrid scaffold structure capable for ACL tissue engineering. The hybrid structure is composed of a biomechanical unit for the compensation of forces, a bio-functional unit to support an enhanced bio-integration and a vital unit including tissue-specific cells of the mid-substance and enthesis to accelerate tissue regeneration. The approach is based on the tailored triphasic scaffold structure, subsequent functionalization and cell seeding strategies already established in the parent project.To complement the embroidered scaffolds, further functional units such as cell barriers or control structures are included requiring technological advancement, adaption and optimization of the embroidery process along with the applied materials. Bio-integration could be enhanced by a novel method of fluorinating the surface of the synthetic polymer in a gaseous phase as well as by infiltrating collagen preparations into the textile structure. The collagen preparations are processed to stable foams performing an interconnected and aligned pore system inside the textile structure. A scientific question addressed here is the enhanced cell adherence on the fluorinated surfaces of the synthetic polymers. The novel hybrid structures will be seeded with small spheroids prepared by the hanging-drop method already established in the parent project. The hybrid structures seeded with different cell types will be mechanically stimulated and an optimized protocol will be established to the benefit of all cell types of ACL enthesis and mid-substance. Co-cultivation with osteogen and chondrogen differentiated as well as ligament cells will be performed in vitro. Additionally, the positive effect of a cell barrier on the prevention of cell migration and the formation of an enthesis will be studied. An optimized procedure will be chosen and evaluated for ligamentogenesis in a dynamic nude mice model as well as in an orthotopic rabbit ACL reconstruction model.At the end of the project a procedure, comprising the manufacturing of the biomechanical, the bio-functional and the bio-integrative units as well as the cell seeding and cultivation strategies, will be determined directly applicable for a subsequent large animal testing.