Anterior cruciate ligament (ACL) injuries occur most frequently in sports knee injuries, and most injured patients are indicated for ACL reconstruction. Standard treatment of ACL reconstruction uses the autologous knee flexor tendon as a graft for reconstruction, but it is often difficult to obtain adequate grafts from women and short patients. Besides, for patients suffering from recurrent rupture of the ACL, the autologous knee flexor tendon would not be available.
The graft, intended to be implanted for ACL reconstruction, is made from a bovine tendon and is used as a substitute of the autograft made from the patient’s own tendon.
It is an artificial ligament using animal-derived tissue as a starting material and adapts its own decellularization treatment and sterilization method, thereby maintaining the native ligament durability and biocompatibility. After implantation, the graft is also biodegradable and the host's own cells migrate from the surrounding tissues into the graft. Therefore, it enables successful anterior cruciate ligament reconstruction to be achieved as an alternative implant device without negative immunological adverse effects and better healing results.
“Decellularization of animal tissue” is the removal of cellular components which causes graft rejection in humans. The features of the decellularization technology include the following two simultaneous processes:
(1) Microwave irradiation, which takes advantage of the resonance phenomenon of water molecules, and
(2) Circulating surfactant that dissolves the cell membranes present in the pulsatile blood pressure and blood flow environment.
With this technology, it is now possible to remove the cell nucleus while maintaining the tendon’s original collagen hierarchical structure and tissue strength, even for tendons with a diameter of over 10 mm and/or a length of over 20 cm.
For lyophilization treatments and ethylene oxide gas sterilization, new technologies are also developed and utilized:
(1) Pre-treatment of acellularized tissue with disaccharides solution, and
(2) Ethylene oxide gas sterilization at low reaction temperatures
In order to maintain the strength of the tissue which is mainly composed of collagen, ethylene oxide gas sterilization was selected instead of gamma-ray sterilization. Under standard lyophilization treatments, the tissue remains solid even after long durations of saline solution immersion, but the current technology allows for sufficient hydration of the tissue and retention of the mechanical properties of the tissue after hydration.
This technique can be applied in the field of orthopedics to ACL reconstruction that requires an autograft made from the patient's own tendon.
ACL injury occurs most frequently in sports knee injuries and it is often damaged by a decelerating motion, such as the landing of a jump or a sudden change of direction. The annual number of surgical cases for ACL injury is reported to be approximately 18,000 in Japan and 170,000 in the United States. It is estimated that about 4 in 10,000 people will be injured in the general population per year.
The standard of care (the primary option) is patient autologous tendons worldwide. The other options are allograft (from donation) and synthetic fabrics; however, availably of allograft is limited, and outcome of synthetic fabric are not acceptable. Therefore, the grafts from decellularized animal tissue would have very high potential to be the primary option for ACL reconstruction.