Augmentation of Anterior Cruciate Ligament Reconstruction Using Mesenchymal Stem Cells and Collagen Matrix Carrier

Study Overview
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Brief Summary
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The goal of this observational study is to compare patient outcomes for reconstructive surgery of ACL tears. This study utilizes two randomized groups, one being the control group that receives standard ACL reconstructive surgery, while the other is the test group at will receive an injection of stem cells taken from elsewhere within the body. The main objectives are to determine the usefulness of stem cells as a cost-effective implant in reconstructive surgery and to determine if the stem cells provide more optimized healing outcomes. Participants will: Receive ACL reconstructive surgery as normal One-half of the participants will receive stem cells at the repair site as the test group All participants will have 3, 6, 9, 12, 18, and 24 month followups to chart their recovery progress Thus, the outcomes of the group receiving stem cell injections will be compared directly with the outcomes of the standard ACL reconstructive care group.

Detailed Description
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The primary objective of this study is to develop a cost-effective, autologous biologic augmentation technique for ACL reconstruction. The technique involves encasing MSCs harvested from the patient's ACL stump tissue with the GraftNet device in a porous bovine collagen matrix carrier around the ACL autograft. This study is key to determining a reproducible and effective autologous biologic augmentation technique that can be utilized at the point-of-care during ACL reconstruction surgery. FTA results as well as measurements from MRI evaluation will be recorded and utilized to quantify the healing and ACL graft maturation processes. MRI evaluation will be performed in accordance with accepted ACL imaging protocols. This data will then be compared to FTA results and MRI evaluation from patients who did not undergo the bioaugmentation technique for ACL reconstruction. Study design will be a prospective, blinded randomized, single center trial. Patients at the Andrews Institute who meet the inclusion criteria will have the study explained in detail and informed consent will be obtained as outlined below. Fifty patients will be blinded, randomized, and undergo a Bone-Patellar Tendon-Bone (BTB) ACL reconstruction surgery. Twenty-Five randomized patients will receive standard of care (SOC) BTB ACL reconstruction surgery. Twenty-Five randomized patients will receive BTB ACL reconstruction surgery augmented with the patient's ACL stump tissue harvested with the GraftNet device and a porous bovine collagen matrix carrier around the ACL autograft. At each follow up visit after ACL reconstruction, patient reported outcome measures (PROMs) will be collected by the research team to assist in assessing the overall health and rehabilitation of each participant. The following patient reported outcomes will be collected in written or electronic format after informed consent has been obtained from each participant:Tampa Scale of Kinesiophobia, International Knee Documentation Committee Subjective Knee Evaluation Form (IKDC), Patient Reported Outcome Measurements Information System (PROMIS), Single Assessment Numeric Evaluation (SANE), and Magnetic Resonance Imaging (MRI).

Official Title
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A Randomized, Single Blinded Study of the Augmentation of Anterior Cruciate Ligament Reconstruction Using Stump-Derived Mesenchymal Stem Cells Versus Standard of Care Anterior Cruciate Ligament Reconstruction

Conditions
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ACL Tear

Intervention / Treatment
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* Procedure: ACL reconstruction
* Procedure: Mesenchymal stem cell implantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients between the ages of 14 and 50 who are scheduled to have ACL reconstruction by one of the investigating physicians Exclusion Criteria: Patients requiring ACL and posterior cruciate ligament combined surgery Patients with a history of an autoimmune disease, diabetes, a blood/clotting disorder History of previous surgery on the injured knee Patients outside of the acceptable age range of this study

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 50 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
Interventional Model Description: Participants are randomized into one of two groups, the first group receiving stump stem cell infusion and the second group receiving standard of care ACL reconstruction
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACL reconstruction utilizing stump-derived mesenchymal stem cells<br>This is the test group of this study. These participants will receive the augmented ACL reconstruction treatment involving extraction and injection of mesenchymal stem cells. Stem cell tissue will be harvested from each participant using the GraftNet device intraoperatively. During the intra-articular preparation phase of the reconstruction, the stem cell tissue will be applied to the ACL graft using a bovine collagen matrix. | Procedure: ACL reconstruction<br>* Orthopedic surgical operation in which a ruptured anterior cruciate ligament is repaired and reattached to the muscle connection points with a graft, a fashioned ligament that is meant to serve as a replacement for the ruptured muscle tissue.<br>Procedure: Mesenchymal stem cell implantation<br>* Stem cells are to be extracted from tissue at the stump of the ACL attachment point and inserted on the graft in the hopes of improving healing response<br>|
| Other: Standard of care ACL reconstructive surgery<br>This is the control group of this study. These participants will receive standard ACL reconstructive surgery without any augmentations. | Procedure: ACL reconstruction<br>* Orthopedic surgical operation in which a ruptured anterior cruciate ligament is repaired and reattached to the muscle connection points with a graft, a fashioned ligament that is meant to serve as a replacement for the ruptured muscle tissue.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessing functional movement using Functional Testing Algorithm | Battery of tests used to determine the participant's capability of movement during the post-op recovery process; provides physical functional evidence of biomechanical recovery | 3 months post-operative | 
| Assessing functional movement using Functional Testing Algorithm | Battery of tests used to determine the participant's capability of movement during the post-op recovery process; provides physical functional evidence of biomechanical recovery | 6 months post-operative | 
| Assessing functional movement using Functional Testing Algorithm | Battery of tests used to determine the participant's capability of movement during the post-op recovery process; provides physical functional evidence of biomechanical recovery | 9 months post-operative | 
| Assessing functional movement using Functional Testing Algorithm | Battery of tests used to determine the participant's capability of movement during the post-op recovery process; provides physical functional evidence of biomechanical recovery | 12 months post-operative | 
| Assessing functional movement using Functional Testing Algorithm | Battery of tests used to determine the participant's capability of movement during the post-op recovery process; provides physical functional evidence of biomechanical recovery | 18 months post-operative | 
| Assessing functional movement using Functional Testing Algorithm | Battery of tests used to determine the participant's capability of movement during the post-op recovery process; provides physical functional evidence of biomechanical recovery | 24 months post-operative |