Knee Osteoarthritis (Knee OA)
Conditions
Keywords
microfracture, Stromal Vascular Fraction, Cartilage Repair, WOMAC, WORMS, Regenerative Medicine
Brief summary
This prospective, randomized controlled clinical trial aims to evaluate the clinical and radiological effects of combining stromal vascular fraction (SVF) therapy with arthroscopic microfracture in patients with knee osteoarthritis. A total of 50 patients with symptomatic gonarthrosis were randomly assigned to either receive arthroscopic debridement and intra-articular SVF injection alone or SVF injection combined with arthroscopic debridement, microfracture. The primary outcome measures include changes in VAS, WOMAC, and Lysholm scores at 3, 6, 12, and 24 months. Radiological assessment was performed using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system. The study hypothesis is that the combination therapy will result in superior clinical and cartilage regeneration outcomes compared to SVF treatment alone.
Detailed description
This single-center, prospective, randomized controlled clinical study was conducted to compare the efficacy of stromal vascular fraction (SVF) therapy alone versus SVF therapy combined with arthroscopic microfracture in patients diagnosed with knee osteoarthritis (gonarthrosis). A total of 50 patients with symptomatic medial compartment osteoarthritis, classified as Kellgren-Lawrence grade II-III, were enrolled and randomized into two groups: Group A (n=25): Participants initially underwent arthroscopic debridement and microfracture, followed by intra-articular injection of autologous stromal vascular fraction (SVF) Group B (n=25): Participants underwent arthroscopic debridement, after which intra-articular injection of autologous stromal vascular fraction (SVF) was administered. Microfracture was not performed in this group. SVF was isolated from autologous lipoaspirate obtained via mini-liposuction and processed intraoperatively using a closed system. Arthroscopic microfracture was performed with standard technique, targeting cartilage defects in the medial and lateral femoral condyle. Clinical evaluations were performed preoperatively and at 3, 6, 12, and 24 months post-intervention using: Visual Analog Scale (VAS) for pain Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Lysholm Knee Scoring Scale Radiological outcomes were assessed using 3.0 Tesla MRI and scored with the Whole-Organ Magnetic Resonance Imaging Score (WORMS), focusing on cartilage integrity in predefined regions. The primary endpoint was the improvement in WOMAC score.Cartilage morphology based on WORMS at 12 and 24 months. Secondary endpoints included changes in Lysholm and VAS scores. Inter-group comparisons were analyzed using appropriate statistical methods with a significance threshold of p \< 0.05. The study aims to explore whether the addition of microfracture to SVF therapy yields superior clinical and structural benefits, potentially guiding future treatment protocols for early to moderate knee osteoarthritis.
Interventions
PROCEDUREArthroscopic Microfracture Combined with Autologous SVF Injection
This procedure involved arthroscopic debridement and microfracture of the knee joint. After microfracture, autologous SVF, isolated from adipose tissue through mechanical digestion and centrifugation, was administered intra-articularly under sterile conditions
PROCEDUREArthroscopic Debridement Followed by Autologous SVF Injection
This procedure included only arthroscopic debridement of the knee joint. After debridement, autologous SVF, isolated in the same manner from adipose tissue, was injected into the joint space intra-articularly without microfracture.
Sponsors
Istanbul University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Participants were blinded to their treatment allocation throughout the study. Although the operating surgeons were aware of the intervention due to the nature of the surgical procedures, outcome assessment was conducted by an independent radiologist who was blinded to group allocation.
Intervention model description
Two-group parallel design: Group A received arthroscopic microfracture combined with stromal vascular fraction injection, while Group B received stromal vascular fraction injection alone.
Eligibility
Sex/Gender
ALL
Age
49 Years to 71 Years
Healthy volunteers
No
Inclusion criteria
* Patients with stage II-III osteoarthritis of the knee * Patients with a mechanical axis deviation not exceeding 15 mm on the anteroposterior orthoroentgenogram x-ray
Exclusion criteria
* Patients with deformities on anteroposterior and lateral x-ray examinations * Patients with a BMI greater than 35 kg/m2 * Patients diagnosed with secondary gonarthrosis (Rheumatoid arthritis, secondary to trauma) * Patients with a history of intra-articular injections within the last 6 months * Patients with a history of knee joint surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) | Baseline, 3 months, 6 months, 12 months, and 24 months after the intervention | The WOMAC index (range: 0-96) is a validated questionnaire evaluating pain, stiffness, and physical function in osteoarthritis patients. Higher scores indicate worse symptoms. This outcome measures change in WOMAC score following SVF therapy with or without microfracture. |
| Change in WORMS (Whole-Organ Magnetic Resonance Imaging Score) | Baseline and 12,24 months after the intervention | The WORMS cartilage subscore (range: 0-84) is a semiquantitative MRI-based system assessing the morphology and integrity of articular cartilage in the knee joint. Higher scores indicate more severe cartilage damage. This outcome specifically evaluates radiological changes in cartilage structure after SVF therapy with or without microfracture. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Lysholm Knee Score | Baseline, 3 months, 6 months, 12 months, and 24 months after the intervention | The Lysholm Knee Score (range: 0-100) is a validated tool assessing knee function, including pain, instability, and swelling. Higher scores indicate better knee function. |
| Change in VAS (Visual Analog Scale) for Pain | Baseline, 3 months, 6 months, 12 months, and 24 months after the intervention | The VAS for pain (range: 0-10) is a subjective scale assessing pain intensity, where 0 = no pain and 10 = worst imaginable pain. Higher scores indicate worse pain. |
Countries
Turkey (Türkiye)
Participant flow
Recruitment details
Patients with moderate knee osteoarthritis were recruited from Istanbul University orthopedics outpatient clinics between 2022-2025. A total of 50 patients were screened and randomized.All participants met inclusion criteria and provided informed consent.
Pre-assignment details
Seven patients were excluded before assignment due to not meeting eligibility criteria (n=4) or declining participation (n=3).
Participants by arm
| Arm | Count |
|---|---|
| Microfracture Plus SVF Group Participants underwent arthroscopic debridement and microfracture, followed by intra-articular injection of autologous stromal vascular fraction (SVF) derived from adipose tissue. | 25 |
| SVF Only Group Participants underwent only arthroscopic debridement. Following this, autologous SVF derived from adipose tissue was injected intra-articularly, without performing microfracture. | 25 |
| Total | 50 |
Baseline characteristics
| Characteristic | Microfracture Plus SVF Group | SVF Only Group | Total |
|---|---|---|---|
| Age, Continuous | 58.8 Years STANDARD_DEVIATION 5.6 | 58.6 Years STANDARD_DEVIATION 5.3 | 58.7 Years STANDARD_DEVIATION 5.4 |
| Baseline Lysholm Score | 47.20 Score STANDARD_DEVIATION 5.02 | 47.80 Score STANDARD_DEVIATION 5.02 | 47.50 Score STANDARD_DEVIATION 4.97 |
| Baseline VAS (Pain) | 6.56 Score STANDARD_DEVIATION 1 | 6.44 Score STANDARD_DEVIATION 1 | 6.50 Score STANDARD_DEVIATION 0.99 |
| Baseline WOMAC Score | 50.92 Score STANDARD_DEVIATION 7.49 | 50.04 Score STANDARD_DEVIATION 7.38 | 50.48 Score STANDARD_DEVIATION 7.37 |
| Baseline WORMS(Whole-Organ Magnetic Resonance Imaging Score) | 68.72 Scores on a scale STANDARD_DEVIATION 2.48 | 69.04 Scores on a scale STANDARD_DEVIATION 2.62 | 68.88 Scores on a scale STANDARD_DEVIATION 2.53 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Turkey | 25 Participants | 25 Participants | 50 Participants |
| Sex: Female, Male Female | 17 Participants | 19 Participants | 36 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 25 |
| other Total, other adverse events | 0 / 25 | 0 / 25 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 |
Outcome results
Primary
Change in WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index)
The WOMAC index (range: 0-96) is a validated questionnaire evaluating pain, stiffness, and physical function in osteoarthritis patients. Higher scores indicate worse symptoms. This outcome measures change in WOMAC score following SVF therapy with or without microfracture.
Time frame: Baseline, 3 months, 6 months, 12 months, and 24 months after the intervention
Population: All randomized participants (n=50; 25 in the Microfracture plus SVF group and 25 in the SVF only group) completed the 24-month follow-up and were included in the final analysis. Therefore, the analysis population matches the assigned population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Microfracture Plus SVF Group | Change in WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) | Outcomes at 12 Months | 33.88 Score | Standard Deviation 5.98 |
| Microfracture Plus SVF Group | Change in WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) | Outcomes at 6 Months | 34.16 Score | Standard Deviation 16.32 |
| Microfracture Plus SVF Group | Change in WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) | Outcomes at 24 Months | 33.48 Score | Standard Deviation 6.4 |
| Microfracture Plus SVF Group | Change in WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) | Outcomes at 3 Months | 49.52 Score | Standard Deviation 7.58 |
| SVF Only Group | Change in WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) | Outcomes at 24 Months | 47.08 Score | Standard Deviation 7.68 |
| SVF Only Group | Change in WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) | Outcomes at 6 Months | 49.96 Score | Standard Deviation 7.87 |
| SVF Only Group | Change in WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) | Outcomes at 12 Months | 47.16 Score | Standard Deviation 7.02 |
| SVF Only Group | Change in WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) | Outcomes at 3 Months | 50.60 Score | Standard Deviation 8.64 |
Primary
Change in WORMS (Whole-Organ Magnetic Resonance Imaging Score)
The WORMS cartilage subscore (range: 0-84) is a semiquantitative MRI-based system assessing the morphology and integrity of articular cartilage in the knee joint. Higher scores indicate more severe cartilage damage. This outcome specifically evaluates radiological changes in cartilage structure after SVF therapy with or without microfracture.
Time frame: Baseline and 12,24 months after the intervention
Population: All randomized participants (n=50; 25 in the Microfracture plus SVF group and 25 in the SVF only group) completed the 24-month follow-up and were included in the final analysis. Therefore, the analysis population matches the assigned population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Microfracture Plus SVF Group | Change in WORMS (Whole-Organ Magnetic Resonance Imaging Score) | Outcomes at 24 Months | 40.64 Scores on scale | Standard Deviation 2.72 |
| Microfracture Plus SVF Group | Change in WORMS (Whole-Organ Magnetic Resonance Imaging Score) | Outcomes at 12 Months | 41.28 Scores on scale | Standard Deviation 2.48 |
| SVF Only Group | Change in WORMS (Whole-Organ Magnetic Resonance Imaging Score) | Outcomes at 12 Months | 68.76 Scores on scale | Standard Deviation 2.8 |
| SVF Only Group | Change in WORMS (Whole-Organ Magnetic Resonance Imaging Score) | Outcomes at 24 Months | 66.80 Scores on scale | Standard Deviation 6.25 |
Secondary
Change in Lysholm Knee Score
The Lysholm Knee Score (range: 0-100) is a validated tool assessing knee function, including pain, instability, and swelling. Higher scores indicate better knee function.
Time frame: Baseline, 3 months, 6 months, 12 months, and 24 months after the intervention
Population: All randomized participants (n=50; 25 in the Microfracture plus SVF group and 25 in the SVF only group) completed the 24-month follow-up and were included in the final analysis. Therefore, the analysis population matches the assigned population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Microfracture Plus SVF Group | Change in Lysholm Knee Score | Outcomes at 6 Months | 47.40 Score | Standard Deviation 5.02 |
| Microfracture Plus SVF Group | Change in Lysholm Knee Score | Outcomes at 12 Months | 82.20 Score | Standard Deviation 5.02 |
| Microfracture Plus SVF Group | Change in Lysholm Knee Score | Outcomes at 24 Months | 82.00 Score | Standard Deviation 4.08 |
| Microfracture Plus SVF Group | Change in Lysholm Knee Score | Outcomes at 3 Months | 46.80 Score | Standard Deviation 4.76 |
| SVF Only Group | Change in Lysholm Knee Score | Outcomes at 24 Months | 82.40 Score | Standard Deviation 5.61 |
| SVF Only Group | Change in Lysholm Knee Score | Outcomes at 3 Months | 47.6 Score | Standard Deviation 5.02 |
| SVF Only Group | Change in Lysholm Knee Score | Outcomes at 12 Months | 82.20 Score | Standard Deviation 5.02 |
| SVF Only Group | Change in Lysholm Knee Score | Outcomes at 6 Months | 46.40 Score | Standard Deviation 4.68 |
Secondary
Change in VAS (Visual Analog Scale) for Pain
The VAS for pain (range: 0-10) is a subjective scale assessing pain intensity, where 0 = no pain and 10 = worst imaginable pain. Higher scores indicate worse pain.
Time frame: Baseline, 3 months, 6 months, 12 months, and 24 months after the intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Microfracture Plus SVF Group | Change in VAS (Visual Analog Scale) for Pain | Outcomes at 3 Months | 5.60 Score | Standard Deviation 1.04 |
| Microfracture Plus SVF Group | Change in VAS (Visual Analog Scale) for Pain | Outcomes at 6 Months | 5.96 Score | Standard Deviation 1.17 |
| Microfracture Plus SVF Group | Change in VAS (Visual Analog Scale) for Pain | Outcomes at 12 Months | 2.76 Score | Standard Deviation 0.78 |
| Microfracture Plus SVF Group | Change in VAS (Visual Analog Scale) for Pain | Outcomes at 24 Months | 2.76 Score | Standard Deviation 0.66 |
| SVF Only Group | Change in VAS (Visual Analog Scale) for Pain | Outcomes at 24 Months | 5.40 Score | Standard Deviation 0.91 |
| SVF Only Group | Change in VAS (Visual Analog Scale) for Pain | Outcomes at 3 Months | 6.28 Score | Standard Deviation 1.06 |
| SVF Only Group | Change in VAS (Visual Analog Scale) for Pain | Outcomes at 12 Months | 5.76 Score | Standard Deviation 1.13 |
| SVF Only Group | Change in VAS (Visual Analog Scale) for Pain | Outcomes at 6 Months | 6.16 Score | Standard Deviation 1.07 |