Prospective Clinical Feasibility Study of a Poly-L-Lactic Acid Scaffold in Primary Anterior Cruciate Ligament Reconstruction with Three-Year Follow Up - Abstract
Background: This study assessed the safety and feasibility of the L-C Ligament, a bioresorbable scaffold, for ACL reconstruction. This acellular scaffold is constructed of poly (Llactic) acid (PLLA) microfilaments that are three-dimensionally braided together to direct ligament regeneration. Purpose: To evaluate patient outcomes up to 3-years follow-up following ACL reconstruction with the PLLA scaffold. Methods: Fifteen patients with ruptures of the ACL (<18 weeks after injury) were enrolled in this prospective, first-in-human study. The PLLA scaffold was used to anatomically reconstruct the ACL using outside-in technique with titanium interference screws. The primary endpoint of the study was the incidence of graft ruptures. Secondary endpoints included device-related adverse event rates, subjective patient-reported outcomes (2000 IKDC scale, KOOS pain, Tegner, and Lysholm scores), clinical function (Lachman, KT-1000, pivot shift, anterior drawer, and single leg hop test), and imaging analyses (MRI and CT). In the case of graft rupture, biopsies were taken from the intra-articular region and processed for histological and molecular weight analysis. Results: This firstinhuman study of primary ACL reconstruction, the PLLA scaffold demonstrated an improvement in patient-reported and clinical function scores at 12 months (IKDC: 90.1 ± 13.5; KOOS: 94.4 ± 10.7) over baseline (IKDC: 60.2 ± 12.7? KOOS: 75.6 ± 15.4). IKDC Physical Knee exam also showed the patients to have normal or nearly normal (Grade A or B) function at 12 months, with >80% of patients having normal laxity according to KT-1000 measurements. No infections, synovitis, or allergic reactions were reported for the duration of the study. However, review of MRI at 6 and 12 Months showed a hyper-intense signal indicative of chronic inflammation and in turn incomplete ligament maturation. After returning to activity and sport, five patients experienced graft ruptures between 12 and 36 months. Histological analysis of graft biopsies obtained during revision surgery revealed connective tissue ingrowth into the scaffold, presence of new vasculature, and a peripheral synovial layer. A chronic inflammatory response was observed adjacent to remnant polymer, with molecular weight analysis showed 87% loss at 35 months. The 10 remaining patients continue to report normal ACL function. Conclusion: The first-in-man study of a PLLA scaffold for primary ACL reconstruction demonstrated the feasibility of a tissue-engineering approach; however, tissue remodeling was incomplete in this 15-patient cohort over 36 months. Five patients experienced ruptures between 12 and 36 months, suggesting insufficient load-bearing capacity of the new ligament tissue in the presence of a resorbing scaffold. Further innovation is required to optimize scaffold properties to achieve long-term clinical efficacy with a bioresorbable implant for ACL reconstruction.