Microfracture Versus Adipose Derived Stem Cells for the Treatment of Articular Cartilage Defects

Study Overview
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Brief Summary
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The purpose of this study is to compare two biologic methods for the treatment of articular cartilage defects in the knee. The first method, microfracture, is the standard of care and is routinely used to recruit cells from the subchondral bone marrow to the site of cartilage loss. The second method is the application of adipose-derived stem cells (ADSCs) to the defect site. In theory, ADSCs on a collagen scaffold should enable the delivery of more specific progenitor cells to the site of injury, resulting in better regeneration and integration of articular cartilage at the site of a defect as compared to the microfracture method.

Detailed Description
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Patients enrolled in the ADSC cohort will undergo the following procedures: arthroscopic resection of approximately 5cc of the infrapatellar fat pad using a motorized shaver (standard use in arthroscopy). Fat will be collected in a sterile Aquavage Collection System (AV1200, MD Resources, Livermore, CA) and kept sealed until processing. Fat will then immediately be processed in the Harvest Adiprep System to separate a population of ADSCs. This system concentrates an average of 5 x 105 cells/ml. All specimens will be processed using routine sterile procedures within the operating room; cells destined for implantation will not leave the operating room. Concurrently, patients will undergo arthroscopy and similar preparation of the chondral defect and removal of the calcified cartilage layer. However, no puncture of the subchondral bone will be performed. A layer of fibrin glue (Tisseel) will be placed at the base of the defect to seal off any bleeding from the subchondral plate followed by the application of the acellular dermal matrix (Allopatch HD, MTF Corporation, Edison, NJ, USA)and ADSCs. An additional layer of Tisseel will then be applied over the cells and matrix. No additional fixation will be applied. The matrix and cells will be recessed below the articular surface by an average of 1mm. They will then complete outcome questionnaires and additional MRI scans at 6, 12, and 24 months post-operatively.

Official Title
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Randomized Controlled Trial of Microfracture Versus Adipose Derived Stem Cells for the Treatment of Isolated Articular Cartilage Defects

Conditions
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Degenerative Lesion of Articular Cartilage of Knee

Intervention / Treatment
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* Procedure: ADSC Application
* Procedure: Microfracture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be between ages 18 and 50 years. Must have a discrete, contained chondral defect less than 400mm^2 located on the medial or lateral femoral condyle Must have overall neutral lower limb mechanical alignment (<5 degrees varus or valgus). Exclusion Criteria: Ages younger than 18 years and older than 50 years. If they have undergone previous chondral procedures If they have pre-existing osteoarthritis (Kellegren-Lawrence Grade ≥2) If they have a BMI >30.

Ages Eligible for Study
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Minimum Age: 18 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADSC Application<br>Patients undergo an arthroscopic surgical procedure, ADSC application, followed by physical therapy. | Procedure: ADSC Application<br>* Patients will undergo arthroscopic resection of approximately 5cc of the infrapatellar fat pad, which will be collected for processing for a population of ADSCs. Patients will undergo arthroscopy and preparation of the chondral defect and removal of the calcified cartilage layer. Tisseel Fibrin glue will be placed at the base of the defect side, followed by the application of the acellular collagen dermal matrix, ADSCs, and an additional layer of fibrin glue.<br>|
| Active Comparator: Microfracture Arm<br>Patients undergo an arthroscopic surgical procedure, microfracture, followed by physical therapy. | Procedure: Microfracture<br>* Microfracture surgery is the standard of care for articular cartilage lesions. Patients will undergo arthroscopy with standard technique of microfracture preparation, including the creation of vertical, stable defect edges and removal of the calcified cartilage layer. A microfracture awl will then be used to perform the microfracture technique (6mm below the subchondral plate).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health Scores on the KOOS Questionnaire | The Knee Osteoarthritis Outcome Score (KOOS), a standard outcome questionnaire for the assessment of health-related quality of life, will be completed. | Completed at baseline, 6 months, 12 months, and 24 months post-operatively. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Activity Level on the Tegner Activity Scale | The Tegner Activity scale, a standard outcome questionnaire for assessment of activity levels, will be completed. | Completed at baseline, 6 months, 12 months, and 24 months post-operatively. | 
| Cartilage Composition Assessment by MRI Scan | Magnetic resonance imaging scans consisting of routine clinical sequences and T2 and T1p quantitative maps will be conducted. T1p and T2 mapping will be used to assess regenerative cartilage composition compared to surrounding normal cartilage, surface integrity, average cartilage thickness, and the percentage to which the defect is filled. | Assessed at baseline, 6 months, 12 months, and 24 months post-operatively. | 
| Functionality Scores on the Lysholm Scale | The Lysholm Scale, a standard outcome questionnaire for assessment of knee functionality, will be completed. | Completed at baseline, 6 months, 12 months, and 24 months post-operatively. | 
| Pain Scores on the Visual Analog Scale (VAS) | The Visual Analog Scale, a standard outcome questionnaire for assessment of pain levels, will be completed. | Completed at baseline, 6 months, 12 months, and 24 months post-operatively. | 
| Health Scores on Veterans-Rand (VR-12) Survey | The Veterans-Rand survey, a standard outcome questionnaire for assessment of health and quality of life, will be completed. | Completed at baseline, 6 months, 12 months, and 24 months post-operatively. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cartilage/transplantation, cartilage, articular/injuries, cartilage, articular/surgery, chondrocytes/cytology, knee injuries/surgery, knee joint/surgery, orthopedic procedures/methods, tissue engineering, tissue scaffolds, arthroscopy/methods, chondrocytes/transplantation, adipose tissue/cytology, cartilage, articular/cytology, chondrogenesis/physiology, osteogenesis/physiology, stem cell transplantation/methods, stem cells, tissue engineering/methods, cartilage, articular/pathology, chondrocytes/pathology, knee joint/pathology, platelet-rich plasma