Development of a living anterior cruciate ligament replacement: Cellular repopulation of a decellularized allograft matrix

Damage to the ligaments that stabilize the knee is the most common knee injury requiring surgical treatment. Surgical treatment can involve repair or replacement of the ligament. In the case of one of the ligaments most often injured¿the anterior cruciate ligament (ACL)¿repair is not possible due to its poor healing. Therefore, the only viable treatment is to replace the damaged tissue. To date, the most successful replacements for the ACL are derived from tendonous tissues taken from the patient's knee or leg. These replacements, however, cannot match the properties of the original ACL tissue and only restore proper knee stability and function for a short period of time. Further, the harvesting of healthy tissue from the patient most often results in complications. As an alternative to harvesting healthy tendonous tissue from the patient, we propose to use ACL tissue harvested from cadeveric donors (allografts). We are developing methods to safely extract cellular materials from the allografts¿thereby removing the source of immunological incompatibility¿to allow transplantation. Further, we will be developing ways to seed these "decellularized" ACL donor allografts with cells taken from the patient receiving the graft to recreate a compatible "living" ACL replacement. These grafts would have advantages over current treatments including (i) avoiding the harvesting of healthy tissue and associated complications, (ii) avoiding immune complications, and (iii) regenerating the structure and function of the original ACL. If successful, this approach may be extended to replace other tissues such as skin, tendon, and blood vessels