Management of Focal Cartilage Lesions of the Knee: The Benefits of an Autograft Procedure

Обзор

Cartilage is a tissue whose primary function is to transmit and distribute loads when joints are under stress. It acts as a buffer between bones at the joints. Over time, or due to diseases and/or trauma, this surface can disappear, leading to pain and limited movement. Cartilage lesions are particularly difficult to treat because cartilage has a limited capacity for regeneration. When cartilage lesions are characterized by a localized defect, several surgical techniques are available to restore cartilage tissue to the affected area. The most frequently used surgical technique is bone marrow stimulation, also known as microfracture. The cartilage lesion is debrided, the subchondral bone exposed, and then a punch is used to perforate the subchondral bone, allowing a clot to form within the defect. This clot will proliferate and differentiate into scar tissue. However, this cellular differentiation results in fibrocartilaginous tissue rather than hyaline cartilage, sometimes with disappointing clinical outcomes. Other techniques for cartilage restoration exist and are used routinely, including more biological techniques such as Minced Cartilage Implantation (MCI). Autologous cartilage is first harvested from around the defect, chopped into very small fragments, and then reimplanted. Cartilage fragmentation activates cell proliferation and migration, followed by the synthesis of an extracellular, cartilaginous matrix. The effectiveness of this fragmentation is increased with fine fragments (\<0.3 mm). Cell proliferation and activity appear to be stimulated by the systematic addition of PRP (Platelet-Rich Plasma) during the MCI procedure. The expected benefit of an MCI approach lies in clinical improvement and better cartilage regeneration (observed on imaging) compared to microfracture. The objective is to conduct a controlled, randomized, blinded study (blinded to both the patient and the MRI assessor of the bone graft) to determine the benefit of an MCI approach versus microfracture.

Подробное описание

Objective : Primary objective: To demonstrate the benefit of the MCI approach in terms of lesion filling at 24 months post-surgery.

Secondary objectives:

* To demonstrate the clinical benefit (based on functional scores and the need for re-intervention) of the MCI approach at different follow-up visits. * To describe all post-operative complications. * To demonstrate the benefit of the MCI approach in terms of lesion filling at 24 months post-surgery in patients with lesions larger than 2 cm².

Outcome Measures :

Primary endpoint: Bone grafting will be measured by magnetic resonance imaging at 24 months using the MOCART score (Magnetic Resonance Observation of Cartilage Repair Tissue 2.0 Knee Score), which assesses the rate and quality of grafting. The evaluator will be blinded to the randomization arm.

Secondary endpoints:

* Functional scores at baseline, at 3, 9, and 24 months: * Visual Analog Scale (VAS) * Self Knee Value (SKV) * Knee Injury and Osteoarthritis Outcome Score (KOOS score) * and Tegner-Lysholm activity score * Postoperative complications from all causes at each visit * Need for reoperation at 3, 9, and 24 months post-surgery.

Single-center, controlled, randomized, blinded (patient and MRI assessor blinded), two parallel arms with a 1:1 ratio:

* Arm 1: Microfractures * Arm 2: Minced Cartilage Implantation (MCI)

Randomization will be stratified by:

* Age (\< 30 years vs ≥ 30 years) * Lesion size (\< 2 cm² vs ≥ 2 cm²)

Inclusion criteria:

* Male or female, aged over 18 years. * Patient who has signed an informed consent form. * Patient with focal cartilage lesions of the knee, classified as grade 4 on MRI according to the International Cartilage Repair Society classification (exposure of subchondral bone), regardless of their size, and for which surgery is indicated. * Be affiliated with a social security scheme or a beneficiary of such a scheme

Exclusion criteria:

* Revision knee surgery * Body Mass Index (BMI) \> 27 kg/m2 * Joint space narrowing on standard radiographic examination * Refusal of consent * Patient unable to read, write, or understand French * Vulnerable patient according to Article L1121-6 of the French Public Health Code (CSP) * Adult patient under guardianship, curatorship, or legal protection * Patient unable to personally give consent according to Article L.1121-8 of the French Public Health Code (CSP) or an adult protected by law * Pregnant or breastfeeding woman according to Article L1121-5 of the French Public Health Code (CSP) * Patient who has already participated in a study within the last 12 months * Patient already enrolled in another ongoing clinical trial

For patients randomized to the Microfracture arm, the procedure will be as follows: under arthroscopy, the lesion is prepared by debriding it.

Using a specific punch, perforations are made perpendicular to the exposed bone surface.

The technical principles are as follows:

* Perforation depth: approximately 3 to 4 mm, allowing access to the bone marrow, * Regular spacing between perforations: 3 to 4 mm, * Preservation of the integrity of the interfracture bone bridges to avoid excessive weakening of the bone endplate.

For patients randomized to the MCI arm, the procedure will be as follows: during surgery, after visualization and debridement of the lesion, cartilage tissue is harvested from a low-weight, and therefore low-stress, area. This cartilage tissue is then fragmented and mixed with PRP (Platelet-Rich Plasma), collected from the patient's blood. Platelets are unique in that they have a high concentration of universal growth factors, enabling them to heal virtually all organic tissues. Adding PRP to the fragmented cartilage tissue promotes cartilage regeneration and the incorporation of the graft into the lesion. To ensure the graft adheres to the bone tissue, it is secured biologically (with thrombin). Post-operative recovery is typical, with a gradual return to walking and other activities.

The participant participation scheme is as follows:

* Baseline: clinical examination + MRI + self-administered questionnaires * Inclusion and randomization after eligibility verification * Day 0: surgical intervention according to randomization (MCI vs. microfractures) * Discharge from hospital: clinical examination + complications * Post-surgery visit (M3 +/- 1 month): clinical examination + self-administered questionnaires + complications + need for re-surgery * Post-surgery visit (M9 +/- 1 month): clinical examination + self-administered questionnaires + complications + need for re-surgery * Post-surgery visit (M24 +/- 1 month): clinical examination + MRI with MOCART score calculation + self-administered questionnaires + complications + need for re-surgery

To demonstrate a difference in filling rate of 30 points (90% in the MCI arm versus 60% in the Microfractures arm) with a standard deviation of 40%, a type I error rate of 5%, and a power of 80%, 28 evaluable subjects per arm are required. To account for unanalyzable data and the potential for patients lost to follow-up, we propose including a total of 80 subjects (40 per arm) in this study.

Вмешательства

• Процедура Management of focal cartilage lesions of the knee: micro-fracture
  Patients will be randomized in the study to: * Either the Microfracture arm * Or the Minced Cartilage Implantation (MCI) arm
• Процедура Minced Cartilage Implantation (MCI)
  Patients will be randomized in the study to: * Either the Microfracture arm * Or the Minced Cartilage Implantation (MCI) arm

Первичные конечные точки

• Bone grafting [Срок оценки: at 24 months after surgery]

Вторичные конечные точки (6)

• Functional scores [Срок оценки: Baseline, at 3 months, 9 months, 24 months after surgery]
• Functional scores [Срок оценки: Baseline 3 months, 9 months, 24 months after surgery]
• Functional scores [Срок оценки: Baseline 3 months, 9 months, 24 months after surgery]
• Functional scores [Срок оценки: Baseline 3 months, 9 months and 24 months after surgery]
• Post-operative complications [Срок оценки: Immediately after surgery until max. 96 hours after surgery (corresponding to hospital discharge), 3 months, 9 months, 24 months after surgery]
• Re-intervention required [Срок оценки: at 3, 9, and 24 months post-surgery]

Критерии участия

Критерии включения

• Male or female, aged over 18 years.
• Patient who has signed an informed consent form.
• Patient with focal cartilage lesions of the knee, classified as grade 4 on MRI according to the International Cartilage Repair Society classification (exposure of subchondral bone), regardless of size, and for which surgery is indicated.
• Be affiliated with or a beneficiary of a social security scheme.

Критерии исключения

• Revision knee surgery
• Body Mass Index (BMI) > 27 kg/m²
• Joint space narrowing on standard radiographic examination
• Refusal of consent
• Patient unable to read, write, or understand French
• Vulnerable patient according to Article L1121-6 of the French Public Health Code (CSP)
• Adult patient under guardianship, curatorship, or legal protection
• Patient unable to give Personally, their consent according to Article L.1121-8 of the French Public Health Code (CSP) or an adult protected by law
• Pregnant or breastfeeding woman according to Article L1121-5 of the French Public Health Code (CSP)
• Patient who has already participated in a study within the last 12 months
• Patient already enrolled in another ongoing clinical trial

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Франция · 1 центр

• Clinique Louis Pasteur - Louis Pasteur Santé Lorraine — Essey-lès-Nancy

Публикации

• Wylie JD, Hartley MK, Kapron AL, Aoki SK, Maak TG. Failures and Reoperations After Matrix-Assisted Cartilage Repair of the Knee: A Systematic Review. Arthroscopy. 2016 Feb;32(2):386-92. doi: 10.1016/j.arthro.2015.07.025. Epub 2015 Sep 28. PMID 26422710
• Tsuyuguchi Y, Nakasa T, Ishikawa M, Miyaki S, Matsushita R, Kanemitsu M, Adachi N. The Benefit of Minced Cartilage Over Isolated Chondrocytes in Atelocollagen Gel on Chondrocyte Proliferation and Migration. Cartilage. 2021 Jan;12(1):93-101. doi: 10.1177/1947603518805205. Epub 2018 Oct 12. PMID 30311776
• Triana J, Hughes AJ, Rao N, Li ZI, Moore MR, Garra S, Strauss EJ, Jazrawi LM, Campbell KA, Gonzalez-Lomas G. Comparable Clinical and Functional Outcomes Between Osteochondral Allograft Transplantation and Autologous Chondrocyte Implantation for Articular Cartilage Lesions in the Patellofemoral Joint at a Mean Follow-Up of 5 Years. Arthroscopy. 2025 Mar;41(3):745-758. doi: 10.1016/j.arthro.2024.05. PMID 38844011
• Smith L, Jakubiec A, Biant L, Tawy G. The biomechanical and functional outcomes of autologous chondrocyte implantation for articular cartilage defects of the knee: A systematic review. Knee. 2023 Oct;44:31-42. doi: 10.1016/j.knee.2023.07.004. Epub 2023 Jul 27. PMID 37516029
• Schreiner MM, Raudner M, Marlovits S, Bohndorf K, Weber M, Zalaudek M, Rohrich S, Szomolanyi P, Filardo G, Windhager R, Trattnig S. The MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) 2.0 Knee Score and Atlas. Cartilage. 2021 Dec;13(1_suppl):571S-587S. doi: 10.1177/1947603519865308. Epub 2019 Aug 17. PMID 31422674
• Schneider S, Ossendorff R, Holz J, Salzmann GM. Arthroscopic Minced Cartilage Implantation (MCI): A Technical Note. Arthrosc Tech. 2020 Dec 19;10(1):e97-e101. doi: 10.1016/j.eats.2020.09.015. eCollection 2021 Jan. PMID 33532215
• Saris DB, Vanlauwe J, Victor J, Almqvist KF, Verdonk R, Bellemans J, Luyten FP; TIG/ACT/01/2000&EXT Study Group. Treatment of symptomatic cartilage defects of the knee: characterized chondrocyte implantation results in better clinical outcome at 36 months in a randomized trial compared to microfracture. Am J Sports Med. 2009 Nov;37 Suppl 1:10S-19S. doi: 10.1177/0363546509350694. Epub 2009 Oct 21. PMID 19846694
• Salzmann GM, Sah B, Sudkamp NP, Niemeyer P. Reoperative characteristics after microfracture of knee cartilage lesions in 454 patients. Knee Surg Sports Traumatol Arthrosc. 2013 Feb;21(2):365-71. doi: 10.1007/s00167-012-1973-y. Epub 2012 Apr 8. PMID 22484416

Идентификаторы

NCT: NCT07641868 · 2026-A00152-49

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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