Tackling the Challenges of Graft Healing After Anterior Cruciate Ligament Reconstruction-Thinking From the Endpoint.

Pauline Po Yee Lui,Shiyi Yao,Patrick Shu Hang Yung

doi:10.3389/fbioe.2021.756930

Abstract

Anterior cruciate ligament (ACL) tear is common in sports and accidents, and accounts for over 50% of all knee injuries. ACL reconstruction (ACLR) is commonly indicated to restore the knee stability, prevent anterior–posterior translation, and reduce the risk of developing post-traumatic osteoarthritis. However, the outcome of biological graft healing is not satisfactory with graft failure after ACLR. Tendon graft-to-bone tunnel healing and graft mid-substance remodeling are two key challenges of biological graft healing after ACLR. Mounting evidence supports excessive inflammation due to ACL injury and ACLR, and tendon graft-to-bone tunnel motion negatively influences these two key processes. To tackle the problem of biological graft healing, we believe that an inductive approach should be adopted, starting from the endpoint that we expected after ACLR, even though the results may not be achievable at present, followed by developing clinically practical strategies to achieve this ultimate goal. We believe that mineralization of tunnel graft and ligamentization of graft mid-substance to restore the ultrastructure and anatomy of the original ACL are the ultimate targets of ACLR. Hence, strategies that are osteoinductive, angiogenic, or anti-inflammatory should drive graft healing toward the targets. This paper reviews pre-clinical and clinical literature supporting this claim and the role of inflammation in negatively influencing graft healing. The practical considerations when developing a biological therapy to promote ACLR for future clinical translation are also discussed.

Highlights

1.1 Epidemiology of anterior cruciate ligament tears and current managementThe anterior cruciate ligament (ACL) is a band of dense connective tissues that courses from the femur to the tibia, the function of which is to prevent excessive knee anterior–posterior translation and to maintain joint stability (Duthon et al, 2006; Zantop et al, 2006)
IL-6 was significantly elevated in painful ligamentous injury of knee, showed negative correlation with Lysholm knee scores at 2 months, 6 months, and 1 year of follow-up, and showed negative correlation with Tegner level of sports activity at 1 year of follow-up High concentration of IL-6 and MMP-3 in the synovial fluid early post-Anterior cruciate ligament (ACL) injury was associated with aberrant gait biomechanics in the injured limb at 6 months post-ACL reconstruction (ACLR)
Patients that failed to reach the International Knee Documentation Committee scores (IKDC) Patient Acceptable Symptom State (PASS) threshold (n 9, 41%) had significantly greater IL-1α Individuals with lesser biomechanical loading on the ACLR limb at the 6-month follow-up exam, compared with the contralateral limb, demonstrate greater concentrations of plasma MMP-3 and IL-6 early after ACL injury and during the early postoperative period Patients with Remnant Preserved (RP)-ACLR had better knee stability within 3 months which was associated with higher expression of IL-8 in the synovial fluid compared with the patients with conventional ACLR Graft loosening was closely related to increased gene and protein expression of inflammatory cytokines (TNF-α, IL-6, and IL-8) within the first year of ACLR

Summary

Introduction

The anterior cruciate ligament (ACL) is a band of dense connective tissues that courses from the femur to the tibia, the function of which is to prevent excessive knee anterior–posterior translation and to maintain joint stability (Duthon et al, 2006; Zantop et al, 2006). ACL tears can impair knee function and increase the lifetime risk of knee osteoarthritis. Patients without and with meniscal tear had a 0%–13% and 21%–48% higher risk of developing knee osteoarthritis at 10 years after an ACL injury, respectively (Oiestad et al, 2009). The contribution of ACL tears to the burden of degenerative joint disease is substantial, accounting for an increase of 30,000–38,000 patients with symptomatic knee osteoarthritis and an additional 25,000–30,000 total knee arthroplasties each year in the United States. Conservative approaches for the management of ACL tears are poorly accepted by young active individuals. The continued active lifestyles of these individuals often lead to recurrent knee instability, chondral and meniscal injuries, and early onset of osteoarthritis (Raines et al, 2017)

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