Acceleration of ligamentization and osseointegration processes after anterior cruciate ligament reconstruction with autologous tissue-engineered polyethylene terephthalate graft

BACKGROUND: Despite the advantages of excellent mechanical properties for rapid return to sports and early rehabilitation after anterior cruciate ligament (ACL) reconstruction with polyethylene terephthalate (PET) artificial ligament, the graft failure rate during long-term follow-up is relatively high due to poor graft-host incorporation. The purpose of the present study was to investigate the effect of autologous tissue-engineered PET (ATE-PET) grafts on osseointegration and ligamentization after ACL reconstruction. METHODS: Forty-eight New Zealand white rabbits were randomly divided into PET group (n=24) and ATE-PET group (n=24). In the ATE-PET group, the rabbits initially underwent subcutaneous implantation of the PET ligament. Two weeks later, unilateral ipsilateral ACL reconstruction was performed using an ATE-PET graft. In the PET group, the rabbits underwent ACL reconstruction using PET grafts as controls. Macroscopic observation, micro-computed tomography, histological and immunofluorescent staining, and biomechanical tests were conducted to evaluate the effects at 4 and 12 weeks postoperatively. RESULTS: The ATE-PET graft was highly pre-vascularized with myofibroblast aggregation after two weeks of subcutaneous implantation. With regard to the intraosseous part of the graft, the ATE-PET group had significantly higher bone mineral density and bone volume/total volume ratio at 12 weeks. Histologically, the width of the interface between the graft and bone was smaller. Regarding the intra-articular part, thicker tissue coverage with a glossy appearance was observed in the ATE-PET group at 12 weeks on macroscopic observation. Histological staining also showed more collagen fibers grew in the grafts with fewer inflammatory reactions of the ATE-PET group at both 4 and 12 weeks. Immunofluorescently, both α-SMA-positive vessels and α-SMA-positive myofibroblasts were found to be significantly greater around the graft in the ATE-PET group at 4 weeks and markedly declined at 12 weeks. Moreover, the ATE-PET group presented significantly greater failure load and stiffness than the PET group at 12 weeks (53.7±5.4 vs. 42.5±4.5 N, P<0.01; 12.9±3.0 vs. 9.8±1.3 N/mm, P=0.04). CONCLUSIONS: The ATE-PET artificial ligament with pre-vascularization and myofibroblast aggregation could effectively accelerate intra-articular graft ligamentization and intraosseous graft osseointegration, thus enhancing the biomechanical properties after ACL reconstruction in a rabbit model.