Long-term In-vivo Evaluation Of A Resorbable PLLA Scaffold For Regeneration Of The ACL

OBJECTIVES: A synthetic device for ACL reconstruction has long been sought to eliminate co-morbidities of autograft harvest, and variability, potential for disease and allogeneic reaction with allograft. We hypothesized that a PLLA graft and hamstring autograft would regenerate similarly in an ovine model of ACL rupture. METHODS: 125 ACL reconstructions were performed with PLLA grafts in 79 sheep and autograft tendons in 46 sheep. 3 combinations of fixation were used: (1) titanium screws outside-in on tibia, inside-out on femur, (2) screws outside-in on tibia & femur, (3) screw outside-in on the femur, suspension fixation on femur. The PLLA graft was made of 3-D braided fibers with loose braid intra articularly and tight braid for fixation. ACL reconstructions were evaluated 6 weeks through 4 years for clinical function, synovitis, serology, gross reaction, scoring of cartilage and menisci, histology, radiography, micro-CT, MRI, and pathology of organs. Strength of the BLB complex was measured at 6 weeks, and 6 and 12 months. RESULTS: Sheep with PLLA grafts were fully functional post-op; autograft sheep exhibited early morbidity. There was no evidence of synovitis, serology and gross findings were normal. Micro CT, radiographs, MRI, and histology indicated resorption of PLLA grafts and regeneration of the ACL at 12 months. Intra articular histology of PLLA- and auto- grafts showed neo-ligamentization at 3 months, increased collagenous deposition and cellularity with time, a reconstituted ACL at 1 year, and continued maturation. Intra-articularly, PLLA grafts were intact at 6 weeks, and 3 & 6 months, and nearly fully resorbed at 1 year. Histology in the tibial bone tunnel (6 - 48 months) showed the PLLA graft between the screw and aperture filled with new collagenous tissue and tendon-bone healing. At 18, 24, and 48 months, PLLA grafts were intact and encapsulated by bone. Pathology of lymph nodes and organs indicated occasional presence of PLLA particulate. Histology and pathology yielded no adverse findings locally, systemically, or functionally. Biomechanical testing of BLB complexes with inside-out screw fixation on the femur (1) was found to impede healing and function of the PLLA graft. Testing of sheep with suspension fixation (3) showed PLLA grafts to bear a load of 423N (n=6, SD 119N) at 6 weeks, 491N (n=5, SD 116N) at 6 months, and 386N (n=6, SD 220N) at 12 months. In comparison, autograft at 6 weeks, 6 months, and 12 months failed at 111N (n=5, SD 40N), 526N (n=3, SD 185N), and 525N (n=5, SD 171N), respectively. Outside-in fixation for the tibia and femur (2) showed the PLLA graft to bear loads at 6 and 12 months of 320N (n=6, SD 142N) and 601N (n=6, SD 186N). Autograft failed at loads of 358N (n=1) and 422N (n=3, SD 164N). CONCLUSION: Histology was consistent for autograft and PLLA grafts, which is ascribed to the PLLA resembling autograft in early load bearing, gradual resorption and consequent load transfer to newly formed tissue (absence of stress shielding), and maturation of tissue. The difference in resorption in the bone tunnels versus intra articularly is ascribed to the more vascular, biologically dynamic environment of the ACL. Reliable fixation for the PLLA graft was achieved with outside-in screw fixation. Inside-out screw fixation is a contraindication. This is the first study to demonstrate regeneration of the ACL, resorption of an implant intra articularly using a bioresorbable polymer, and is the longest in-vivo evaluation of PLLA in ligament repair of which we are aware.