Among the five ligaments in the knee the anterior cruciate ligament (ACL) is among the most important for stability and also the most commonly injured. Due to a lack of vascularization, the ACL has poor healing potential, therefore moderate to severe damage warrants medical intervention. Ligaments are complex, highly organized tissues; they are longitudinally arranged with a great deal of order that begins at the molecular level and carries through to the tissue level. The components of the ligament and their location and orientation heavily influence the tissue's mechanical behavior. ACL replacements have faced a variety of limitations that prevented their extensive use, including implant fatigue or fraying of the device. In the face of these problems, investigators have begun to examine a variety of matrix based techniques to create options for ACL repair, replacement, and regeneration. This article will discuss ACL structure and mechanics, past replacement options and their limitations, and recent tissue engineered options for ACL repair. These techniques employ a wide variety of designs, materials, and methods to heal damaged ACL tissue or regenerate lost tissue in order to regain full ACL strength and mechanics.
In our general population, sprains and strains account for 5.7 million visits to emergency rooms in the United States each year1. A strain is an injury to the muscle or tendon due to overuse or trauma. A sprain is a damaged or torn ligament resulting from excessive force or motion having been applied to a joint. While a sprain can occur in any joint, the most common joints to be injured are the knees, ankles, and fingers. Not only must the initial injury be managed and considered, but it would also be very beneficial to have a therapy that prevents chronic joint instability. For those who experience an ankle sprain, for example, it is astounding that the majority are likely to suffer a recurrent injury in that joint2. When the injury results in a torn ligament or tendon, either from recurrent injury or serious initial trauma, ligament and tendon surgical replacement or repair are the only current options. It is estimated that between 100,000 and over 250,000 patients have anterior cruciate ligament (ACL) disruptions each year in the United States, with nearly 50,000 of these injuries requiring surgical reconstruction2. Anyone injured with sprains or strains would greatly benefit from a permanent, nonsurgical strengthening of the ligaments or tendons.
Due to their lack of sufficient vascularization, ligament and tendon healing can be lengthy and cumbersome. Proliferative therapy, or prolotherapy, is a somewhat controversial alternative treatment for these injuries that involves the injection of a solution that causes initial small-scale cell damage to induce a robust injury response for tissue healing.The combination of proliferative therapy with carbon nanostructures to produce a living composite ligament may significantly improve healing and stability of damaged ligaments and tendons. While the prolotherapy would induce a healing response that causes the fibroblasts in the tissue to produce new collagen, the addition of the nanostructures could immediately improve strength; preventing further injury and further strengthening the tissue once it has been healed by serving as a constant irritant to fibroblasts to produce structural ECM. In several in vitro studies, the cellular viability of rat patellar tendon fibroblasts in response to the different treatments was measured. After treatment, cell populations experienced increases in cellular viability. The results of these basic studies show the potential of prolotherapy and carbon nanostructures in ligament and tendon healing at a fundamental, cellular level. They also point to another mechanism for tissue healing after prolotherapy that is separate from the body's wound healing cascade.
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