A Translational Approach Towards Ligament Regeneration

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DESCRIPTION (provided by applicant): The anterior crucial ligament (ACL) is the most commonly injured ligament of the knee. Due to inherently poor healing potential and limited vascularization, ACL ruptures do not heal and surgical replacement is often required. Current treatments include the use of autografts (usually with tissue from the patellar tendon or hamstring tendon) or allografts. The limitations associated with the use of autografts include a second surgery, which may cause donor site morbidity and limited availability. Allografts can potentially transmit disease and elicit an unfavorable immunogenic response from the host. Tissue engineering has emerged as an alternative strategy to overcome the limitations of the biological grafts. Our previous studies have led to the development of a tissue engineered synthetic ACL scaffold mimicking the hierarchical structural complexity and mechanics of natural ligament. Recent advances in stem cell technology have shown great potential of bone marrow derived as well as tissue specific cells in promoting the repair and regeneration of connective tissues due to phenotypic plasticity. The goal of this proposal is to develop a translational approach towards accelerated anterior crucial ligament regeneration by combining biomimetic and biofunctional scaffolds with advances in stem cell biology. Our goal will be achieved through the design and optimization of a cell-seeded, three- dimensional (3D) degradable scaffold with structural, mechanical and biological properties similar to natural ACL. 3D braiding in combination with surface modification techniques will be used to create scaffolds with optimized pore structure and surface properties to facilitate cell adhesion, migration, proliferation, and tissue in- growth, as well as mechanical properties comparable to natural ACL. The cell-scaffold constructs will be optimized for enhanced cellular performance and ligamentogenesis both in vitro and in vivo. Our overall hypothesis is that a cell-seeded, degradable, fibrous scaffold that s biomechanically comparable to natural ACL with appropriate surface properties can encourage and support the accelerated regeneration of a new ACL. The successful development of such tissue-engineered constructs will present an alternative to the currently available options for ACL repair.