The Ligamentization Process in Anterior Cruciate Ligament Reconstruction What Happens to the Human Graft? A Systematic Review of the Literature

Background: Surgical anterior cruciate ligament reconstruction using tendon grafts has become the standard to treat the functionally unstable anterior cruciate ligament-deficient knee. Although tendons clearly differ biologically from ligaments, multiple animal studies have shown that the implanted tendons indeed seem to remodel into a ligamentous anterior cruciate ligament-like structure. Purpose: The goal of this study was to systematically review the current literature on the ligamentization process in human anterior cruciate ligament reconstruction. Study Design: Systematic review. Methods: A computerized search using relevant search terms was performed in the PubMed, MEDLINE, EMBASE, and Cochrane Library databases, as well as a manual search of reference lists. Searches were limited to studies examining the healing of the intra-articular portion of the tendon graft based on biopsies of this graft obtained from a living human. Results: Four studies were determined to be appropriate for systematic review, none of them reaching a level of evidence higher than 3. All reports considered autografts. Biopsy specimens were evaluated by light or electron microscopy and analyzed for vascularization, cellular aspects, and appearance of extracellular matrix. All authors universally agreed that the tendon grafts survive in the intra-articular environment. Based on changes observed in the healing grafts with regard to vascularization, cellular aspects, and properties of the extracellular matrix, different chronologic stages in the ligamentization process were discerned. Conclusion: The key finding of this systematic review is that a free tendon graft replacing a ruptured human anterior cruciate ligament undergoes a series of biologic processes termed ligamentization. The graft seems to remain viable at any time during this course. Histologically, the mature grafts may resemble the normal human anterior cruciate ligament, but ultrastructural differences regarding collagen fibril distribution do persist. Different stages of the ligamentization process are described, but no agreement exists on their time frame. Problematic direct transmission of animal data to the human situation, the limited number of reports considering the ligamentization process in humans, and the potential biopsy sampling error attributable to superficial graft biopsies necessitate further human studies on anterior cruciate ligament graft ligamentization.