Functional Tissue Engineering of the Healing Anterior Cruciate Ligament: A Combined Experimental and Computational Approach

The anterior cruciate ligament (ACL) is the most important knee stabilizer and is frequently injured during sports and work related activities. Unfortunately, midsubstance ACL ruptures have a limited healing capacity. As such, surgical reconstruction using soft tissue autografts is often performed. However, long-term follow-up studies have revealed that 20-25% of patients had a less than satisfactory outcome. These negative results have renewed clinical interests in healing of a torn ACL by means of biological stimulation. Thus, there is a need for basic science studies in order to better understand such an approach and also to logically develop an effective functional tissue engineering (FTE) treatment for an injured ACL. The overall objective of this dissertation was to evaluate the positive impact of biological and mechanical augmentation on the healing of the ACL using a combined experimental and computational approach. The ability of an extracellular matrix (ECM) bioscaffold in combination with an ECM hydrogel to enhance ACL healing following suture repair was first demonstrated in the goat model. At 12 weeks of healing, ECM-treatment led to an increase in neo-tissue formation as well as improved biomechanical properties of the healing ACL compared to suture repair alone. Second, as the healing process of the ACL was relatively slow even with ECM treatment, mechanical augmentation to better restore initial joint stability was required. Therefore, a suture augmentation procedure was developed, and improved joint function was achieved versus suture repair alone at the time of surgery. Further, there was increased tissue formation and improved biomechanical properties of the healing ACL at 12 weeks of healing. Finally, as a step toward predicting long-term outcomes following these biological and mechanical augmentation procedures, a preliminary mathematical model was developed to describe the remodeling process of healing ligaments. The results of this work can now be used to guide future experiments using FTE treatments to enhance ACL healing. With a sound scientific basis, it is hoped that such exciting new technologies could then be translated into the clinical arena to improve patient outcome following ACL injuries