Bio ACL Reconstruction Amnion Collagen Matrix Wrap and Stem Cells

Study Overview
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Brief Summary
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Collagen based -membrane derived from amniotic tissue can be used to help reestablish the natural synovial lining of the reconstructed ACL, in effect acting as both a barrier from the synovial fluid and as a scaffold to contain autologous mesenchymal stem cells and growth factors contiguous with the graft, thus aiding and perhaps accelerating the natural maturation and ligamentization process of the implanted graft tissue. Acceleration and improvement in graft maturation and strength would be a significant advancement in sports medicine allowing safer and earlier return to sports and activity

Detailed Description
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Histologic studies have determined that graft ligamentization following anterior cruciate ligament (ACL) reconstruction may take from 6 to 18 months. (1) It has been reported that incomplete graft maturation and incorporation is one cause of clinical graft failure. Animal studies have illustrated improved tendon healing/integration in ACL models augmented with stem cell technologies. (2-4). Basic scientists theorize that optimization of stem cell treatments for tissue regeneration requires that a regenerative triad be employed, i.e., use of a scaffold, stem cells and growth factors. In the intra-articular environment, research has shown that a scaffold such as an amnion wrap is necessary to contain the stem cells and growth factors in close proximity to the ACL graft. (2, 4, 5) The normal, uninjured human ACL is covered by a layer of synovial tissue which contributes to the blood supply and nutrition of the native ACL. It is theorized that the lack of a synovial lining after injury and following traditional ACL reconstruction contributes to slow ligamentization and possible failure of reconstructed grafts.(5) Two studies have demonstrated accelerated maturation and ligamentization of human ACL graft augmented with point of care blood products. (6, 7) In one, leucocyte poor platelet rich plasma was injected directly into the body of the graft. (6) In the other, the platelet derived growth factors were loaded in a gelatin carrier which was wrapped around the graft. (7) In both studies accelerated and increased ligament maturation was documented compared to the controls. Collagen membranes derived from amniotic tissue have been successful to aid healing when used in difficult wounds and meniscal repair surgery. (8, 9) The use of a collagen based -membrane derived from amniotic tissue may be used to help reestablish the natural synovial lining of the reconstructed ACL, in effect acting as both a barrier from the synovial fluid and as a scaffold to contain autologous mesenchymal stem cells and growth factors contiguous with the graft. Thus aiding and perhaps accelerating the natural maturation and ligamentization process of the implanted graft tissue. Acceleration and improvement in graft maturation and strength would be a significant advancement in sports medicine allowing safer and earlier return to sports and activity.

Official Title
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Pilot Study: Augmentation of ACL Reconstruction With Bone Marrow Stem Cells and Amnion Collagen Matrix Wrap

Conditions
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ACL - Anterior Cruciate Ligament Rupture

Intervention / Treatment
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* Other: Bio ACL
* Other: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients between the ages of 18 and 45 who are scheduled to have anterior cruciate ligament reconstruction with autologous grafts by one of the investigating physicians will be screened for participation in this study. Patients must be willing to undergo MRI scans post -operatively at 3, 6, 9 months and 1 year Exclusion Criteria: Patients with prior procedures or significant prior injuries to the same knee are excluded. - - Any patient who will have difficulty obtaining internet access, does not have an active e-mail address, or is unable to comprehend study documents or give informed consent will be excluded. Patient who are unable to complete MRI examinations due to claustrophobia or anxiety will be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Interventional Model Description: ACL harvested for autograft reconstruction of the ACL with either hamstring or patellar tendon grafts. The graft will be wrapped in a collagen wrap and injection with aspirate from the patient's bone marrow. The control group will have standard ACL reconstruction with either hamstring or patellar tendon grafts.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bio-ACL (Amion)<br>Intervention: ACL Autograft Reconstruction with Amion Collagen Scaffold. Stem Cells isolated from bone marrow aspirate from distal femur will be injected inside the Amion Collagen Scaffold. | Other: Bio ACL<br>* Bone marrow aspirate will be centrifuged using the Arthrex Angel system to optimally concentrate the cells for implantation. The graft for the experimental groups will be wrapped with a sterile amnion matrix wrap, supplied by Arthrex<br>* Other names: Amnion;|
| Active Comparator: Control<br>Intervention: Normal ACL Autograft Reconstruction with either patella or hamstring autograft will be performed in the control group. | Other: Control<br>* Normal ACL reconstruction technique with either patella or hamstring autograft<br>* Other names: Standard ACLr;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in ACL | MRI region of interest mapping to produce mean T2 values | 3 months, 6 months, 9 months, 12 months post-op | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in patient-reported pain rating | Visual analog scale will be used to assess pain | 3 months, 6 months, 9 months, 12 months post-op | 
| Changes in Knee injury and Osteoarthritis Outcome Score (KOOS) | Patients will complete KOOS questionnaire on SOS | 3 months, 6 months, 9 months, 12 months post-op | 
| Changes in Short Form 12 (SF-12) patient ratings | Patients will complete SF-12 questionnaire on SOS | 3 months, 6 months, 9 months, 12 months post-op | 
| Changes in Single Assessment Numerical Evaluation (SANE) patient ratings for function | Patients will complete the SANE questionnaire on SOS | 3 months, 6 months, 9 months, 12 months post-op | 
| Marx Activity Scale Rating | Patients will complete the Marx Activity questionnaire on SOS | 12 months post-op | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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amion, stem cell, acl