Regeneration of the Anterior Cruciate Ligament Using Resorbable Metallic and Extracellular Matrix Bioscaffolds

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URL: http://d-scholarship.pitt.edu/25746/

Abstract

The anterior cruciate ligament (ACL) is the most frequently injured knee ligament. Because of its low healing capacity, the current standard of treatment is surgical ACL reconstruction. However, follow-up studies 10 years or more after surgery have shown that patients frequently experience long-term complications, including the early development of osteoarthritis. For this reason, scientists and clinicians have explored alternative treatment methods. With the advent of functional tissue engineering, there has been renewed interest in regenerating an injured ACL using biological augmentation. Still, due to the slow process of ACL healing, mechanical augmentation is also needed to restore stability to the knee immediately after surgery, as well as to load the ACL throughout the healing process.

The purpose of this dissertation was to develop and test a bioresorbable magnesium (Mg) device for mechanical augmentation of a transected ACL in a goat model. First, a ring-shaped device was designed based on the geometry of the goat ACL, and evaluated using a parametric finite element analysis. Then, a robotic/universal force-moment sensor testing system was used to measure the joint stability and in-situ forces in the ACL after repair of the ACL in cadaveric goat stifle joints using the Mg ring (“Mg ring repair”). Under externally applied loads simulating those used in clinical examinations, Mg ring repair could restore joint stability and in-situ forces in the ACL close to normal levels. With these positive findings, in vitro cytocompatibility testing was performed by culturing goat ACL fibroblasts with Mg degradation products. Results on cell proliferation and collagen production suggested that the presence of Mg neither impeded nor enhanced the healing process. Finally, the Mg ring was used to repair a surgically transected ACL in skeletally mature goats alongside biological augmentation using an extracellular matrix (ECM) sheet and hydrogel. In this in vivo study, by 6 weeks post-operatively, neo-tissue had begun to fill in the gap between the transected ends of the ACL. By 12 weeks, the ACL was found to have healed and the continuous neo-tissue was composed of aligned collagen fibers, but without hypertrophy. Biomechanically, the structural properties of the healing femur-ACL-tibia complex were improved compared to ECM treatment alone.

With the results from this dissertation, the advantages of using combined biological and mechanical augmentation to improve healing of a transected ACL have been demonstrated. Building off these findings, future studies can be performed to further enhance ACL healing, as well as extend the application to the healing of other injured ligaments and tendons. It is our hope that in the future, such an approach could be used clinically to improve short and long-term patient outcomes after orthopaedic surgery.

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