Optimizing outcomes of ACL surgery-Is autograft reconstruction the only reasonable option?

Abstract

Anterior cruciate ligament (ACL) injuries occur at a high frequency in the United States with approximately 400,000 ACL reconstructions being performed each year. While ACL reconstruction is our current gold standard of treatment, it does not restore joint motion, or prevent the premature development of posttraumatic osteoarthritis (PTOA) in many patients. Thus, new treatments for an ACL injury, which are less invasive and minimize patient morbidity, including cartilage damage, are highly desirable. We have used a tissue-engineered approach to stimulate ligament healing, to improve upon current treatment options. In this review, we describe and discuss our work moving a tissue engineering strategy from the concept to bench, preclinical, clinical trials and ultimately FDA 510(k) de Novo approval, providing clinicians and patients with a viable alternative to ACL reconstruction.

Keywords: ACL reconstruction; ACL repair; anterior cruciate ligament; bridge-enhanced ACL repair; clinical trial; platelet; posttraumatic osteoarthritis; scaffold-enhanced ACL repair; tissue engineering.

Figure 1:

Scar mass as seen at three months after (A) simple suture repair and (B) scaffold enhanced suture repair where a protein scaffold carrying blood components was placed between the torn ligament ends at the time of repair. Ligaments treated with the scaffold enhancement had a larger and more organized scar mass at three months, with a gross appearance closer to that of an intact porcine ACL. (Figure from Joshi et al, AJSM 2009).

Figure 2:

The yield load and stiffness of the ACL at one year after ACL transection (light blue bar), ACL reconstruction (dark blue bar) and repair enhanced with a scaffold (medium blue, “bridge-enhanced ACL repair”) at one year after surgery. There was no significant difference in mechanical properties between the ACL reconstruction group and the scaffold enhanced repair group. Both reconstruction and scaffold enhanced repair had significantly improved mechanical properties when compared to ACL transection.

Figure 3:

Porcine knees at one year after ACL transection with no further treatment (left panel), ACL reconstruction (center panel) and scaffold-enhanced ACL repair (right panel). In the ACL transection and ACL reconstruction knees, breakdown of the cartilage in the medial femoral condyle is noted (red arrows), while in the scaffold enhanced repair group, there was no significant loss of cartilage integrity (green arrow; adapted from Murray and Fleming, AJSM 2013).

Figure 4:

Magnetic resonance imaging from 9 of the 10 patients in the scaffold enhanced repair group in the first-in-human study (sagittal view, 24 months after scaffold enhanced repair). All subjects had intact anterior cruciate ligament (ACL) fibers from the femoral to tibial attachment sites (arrows). The intact fibers have low signal intensity (black) reflecting highly organized tissue with little free water. (Used from Murray et al, OJSM, 2019).

Figure 5:

Magnetic resonance imaging from 7 of the 10 patients in the autograft ACL reconstruction group in the first-in-human study (sagittal view, 24 months after ACL reconstruction). All subjects had intact grafts coursing from the femoral to tibial tunnels (arrows). The intact fibers have low signal intensity (black) reflecting highly organized tissue with little free water. (Used from Murray et al, OJSM, 2019), with some variability among patients in the amount of highly organized tissue and less organized tissue in the region of the graft.

Figure 6:

Primary outcomes from the 100-patient randomized control trial of autograft ACL reconstruction vs scaffold enhanced repair in young, active patients, including the IKDC score and side-to-side difference in instrumented AP knee laxity measurements at 24 months after surgery. The age-matched norms for IKDC score have a mean of 88 points and the mean difference in AP knee laxity for uninjured patients has been previously reported to be 1 mm.