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2021 ISAKOS Biennial Congress ePoster

Prospective Clinical Feasibility Study Of A Plla Scaffold In Primary Acl Reconstruction With 5-Year Follow-Up

Kees van Egmond, MD, Nieuwleusen, Overijssel NETHERLANDS
Isala Clinic, Zwolle, Europe, NETHERLANDS

The FDA has not cleared the following pharmaceuticals and/or medical device for the use described in this presentation. The following pharmaceuticals and/or medical device are being discussed for an off-label use: Biorez, L-C ligament

Summary

The first-in-man study of a PLLA scaffold for primary reconstruction of the ACL demonstrated the feasibility of an acellular tissue-engineered scaffold;

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Abstract

Introduction

Anterior cruciate ligament (ACL) rupture is one of the most serious sports-related injuries, and nearly 200,000 ACL reconstructions are performed each year in the US. Surgical reconstruction using an autograft remains the gold standard treatment option, but graft selection remains debated and outcomes are affected by the associated donor-site morbidity. The only alternative, allograft, is prone to higher rates of failure, and is inherently limited in quality and availability. To date, a demand remains for a safe, ‘off-the-shelf’ implant for ACL reconstruction, and tissue engineering is one approach that can provide a regenerative solution. Recently, a bioresorbable, acellular, poly(L-lactic acid) (PLLA) scaffold was developed for ACL reconstruction, composed of three-dimensionally braided polymeric microfilaments to guide cellular infiltration and growth of new ligament tissue. Therefore, the object of this study was to assess the safety and feasibility of the PLLA scaffold, for primary ACL reconstruction in a prospective, consecutive, clinical study.

Methods

Fifteen patients (ages 18 to 46 years old) with ACL ruptures were implanted (<18 weeks post-injury) with a PLLA scaffold for ACL reconstruction. The primary endpoint for the study was defined as the absence of graft failure or revision ACL surgery at one year. The study was performed in a highly active patient cohort, with 11 of 15 patients reporting a pre-injury Tegner score of 9 out of 10. Secondary endpoints were determined by safety rates per complications, subjective patient-reported outcomes (2000 IKDC scale, KOOS pain, Tegner, and Lysholm scores), clinical function (Lachman test, KT-1000, pivot shift, anterior drawer, and single leg hop test), and imaging measures (radiographic, MRI, and CT). In the case of graft failure, arthroscopic confirmation was performed prior to or on the same day as revision surgery, and biopsies were taken from the intra-articular region during revision surgery and processed for histological and molecular weight analyses.

Results:. No infections, allergic reactions, or synovitis were reported indicating safety of the implant. Patient-reported IKDC scores (and additional patient-reported outcome measures, Table 1) showed progressive improvement at 6 and 12 months compared to baseline values. Physician-reported clinical evaluations of knee function showed little to no laxity or knee instability at the one year follow-up. However, review of MRI at 6 and 12 months showed a hyper-intense signal indicative of (what?, please complete sentence (Figure 1A). Five graft ruptures occurred between 12 and 36 months follow-up, with one additional rupture at 44 months in a total follow-up of 5 years. Five of the re-ruptures occurred while subjects were playing soccer. One re rupture occurred with a minor trauma. Histological analysis of graft biopsies obtained during revision surgeries revealed a fully cellularized scaffold containing a peripheral synovial cell layer, neovascularization, and robust extracellular matrix. A chronic inflammatory response, marked by foreign body giant cells, was observed adjacent to remnant PLLA (Figure 1A). For the remaining patients, MRI revealed thinning of the ligament and regional hyper-intensity that persisted through 18 and 24 months (Figure 1B). Although 10 individuals without failure at 36 months follow-up continued to report normal ACL function, IKDC scores decreased at 18 months and plateaued through 36 months follow-up though neither were statistically significant. (Table 1).

Discussion And Conclusion

The first-in-man study of a PLLA scaffold for primary reconstruction of the ACL demonstrated the feasibility of an acellular tissue-engineered scaffold; however, tissue regeneration was inconsistent in this 15-patient cohort, resulting in clinically unacceptable failure rates in this limited study. Six patients experienced ruptures between 12 and 60 months, suggesting insufficient load-bearing capacity of the new ligament tissue in the presence of a weakening scaffold. These findings suggest that further innovation is required to optimize scaffold properties in order to achieve long-term clinical efficacy with a bioresorbable implant for ACL reconstruction.