MZG Wire for Augmentation of ACL Reconstruction

Study Overview
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Brief Summary
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Anterior Cruciate Ligament Reconstruction (ACLR) is the standard treatment of ACL injury. The most common grafts used for ACLR are autografts such as hamstring tendon graft. As this process requires the healing of two inhomogeneous tissues -bone with tendon, ACLR can be compromised by poor self-healing response. The use of biodegradable materials as implants to stimulate healing has been developed in orthopaedics for decades. In the ACLR model, our team and others reported that Mg based interference screw could consistently enhance ACLR by upregulating the expression of osteogenic and angiogenic factors experimentally. To improve on the potential insufficient mechanical strength of Mg-based screws in clinical applications, the investigators have developed a magnesium-zinc-gadolinium (MZG) alloy wire as a suture for braiding the tendon graft, following the standard procedure in our centre for the preparation of graft during ACLR. In a validated rabbit model, previous research found the MZG alloy wire showed good formability in material tests when being used as braiding suture, accompanied with the accelerated tunnel healing as shown by significantly more bone formation, and histologically with more regeneration of fibrocartilages at bone tendon healing interface. To further determine its efficacy and safety, MZG wire was tested in comparison with conventional suture in 16 goats as our pilot study. Radiological analysis of the femoral bone tunnel showed the bone volume fraction was significantly higher in MZG alloy wire group, with no significant difference seen in the safety tests. To determine whether the MZG alloy wire and its degradation over time after ACLR can promote graft healing and promote functional recovery in patients, the investigators propose to investigate the effect of using MZG alloy wire as a braiding suture in ACLR in a randomized controlled trial, with 30 patients in the intervention group using MZG alloy wire and 30 in the control group using conventional suture. As a direct measurement, High Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) will be used to measure the microarchitecture in the bone shell tunnel. This novel use of MZG alloy wire as a braiding suture in ACLR, which is a standard procedure for the preparation of graft, that is not related to the fixation of the graft. This can incorporate the benefit of an Mg-based component for its degradation in vivo and release of osteogenic and angiogenic by-products, but without the risk of compromising the fixation of the tendon graft and without the need for additional steps during surgery.

Official Title
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The Clinical Translation of a Biodegradable Magnesium Zinc Gadolinium Wire Developed for Augmentation of ACL Reconstruction, From Benchside to Bedside

Conditions
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Anterior Cruciate Ligament Rupture

Intervention / Treatment
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* Device: Magnesium Zinc Gadolinium alloy wire


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-40 Unilateral ACL tear for primary ACLR (Single bundle, Hamstring) confirmed clinically and radiologically. Exclusion Criteria: Concomitant multiple ligament injuries requiring additional surgical procedures, Preoperative radiographic signs of arthritis, Revision ACLR Femoral tunnel interference screws Contralateral knee with ACL deficiency or reconstruction Medical co-morbidities Long-term steroid intake Non-compliance to our rehabilitation protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MZG Wire group<br>Intervention: Magnesium Zinc Gadolinium (MZG) wire as braiding suture to braid the tendon graft. | Device: Magnesium Zinc Gadolinium alloy wire<br>* MZG wire will be used as a braiding suture to braid tendon graft, which is a standard preparation of graft and is not related to fixation of the tendon graft<br>|
| No Intervention: control group<br>2-0 vicryl suture as control, size and length matched MZG alloy wire | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone shell size | HR-pQCT (ExtremCT II, Scanco, Switzerland) will be used to measure the bone shell size at graft tunnel interface. The involved knees will be investigated. A total of 1344 axial slices with an image matrix of 2304 × 2304 were collected at a nominal isotropic voxel size of 60.7μm. The scan region was defined by the scout view image acquired in the sagittal plane.The total scanning length was 81.6mm which covered the tunnel from proximal tibia to distal femoral condyle (X-ray settings: 68kVp, 1470μA, 100ms integration time, 156mAs per stack (168 slices).Image segmentation will be performed to select the bone shell features at graft tunnel interfaces near femoral and tibial intra-articular apertures with standardized threshold values at a thickness of  2.5 mm (40 slices). Geometric transformation will be performed to adjust for the variations in angle between scanning axis and tunnel axis by a cosine function. | 2 weeks and 3, 6, 12 and 24 months post-operation. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| International Knee Documentation Committee | Consists of 10 questions on symptoms and activity ranging from 0 to 100 where 100 implies perfect knee function. | Pre-operation, 2 weeks and 3, 6, 12 and 24 months post-operation. | 
| Tegner activity score | This is an activity level scaled from 1 (low activity) to 10 (high activity). | Pre-operation, 2 weeks and 3, 6, 12 and 24 months post-operation. | 
| Passive Knee laxity | To measure anterior-posterior knee laxity, the KT-1000 knee ligament arthrometer (MEDmetric Corp, San Diego, CA, USA) will be used. A manual force test will be applied until a 30lb sound signal is activated. Three trials will be performed. A side difference of 3 mm above is considered clinically relevant. | 3, 6, 12 and 24 months post-operation. | 
| Isokinetic muscle strength | The dynamometer (Biodex System 4, Biodex Medical Systems Inc., New York, USA) will be used for measuring Isokinetic muscle strength in N. Subjects will perform a standardized warm-up exercise (5 min cycling) followed by the test. Concentric/concentric contractions of knee extension/flexion will be tested at 60°/s and 180°/s. Subjects will be seated on the dynamometer chair with their hips flexed to 85°. | 3, 6, 12 and 24 months post-operation | 
| Serum myokine evaluation | To evaluate the safety of MZG alloy wire with respect to inflammatory responses, 5 ml blood samples will be collected for C-reactive protein measurement using ELISA kit. Measurements of Ca, Mg, P, Cr, Urea, ALT, AST, TP, ALB, GLB will be taken to monitorpotential effect of the MZG alloy wire. The blood tests will be performed at baseline, day 1 post-op, 2 weeks, 6 weeks and 12 weeks post-op, since the degradation of MZG wire is faster based on our preclinical study results. | Pre-operation, Day 1, 2 and 6 weeks and 3 months post-operation | 
| Single leg hop distance | The average of single leg hop distance in cm with three attempts will be measured during the single leg hop test. | 6, 12 and 24 months post-operation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ACLR, MZG wire, Bone tendon interface healing