Autologous chondrocyte implantation using a bilayer collagen membrane: A preliminary report

Journal of Orthopaedic Surgery, Jun 2003 by Cherubino, P, Grassi, F A, Bulgheroni, P, Ronga, M

ABSTRACT

Purpose. To present preliminary clinical experience with Matrix-induced autologous chondrocyte implantation, a new tissue-engineering technique for treatment of deep cartilage defects, in which autologous chondrocytes are seeded on a tridimensional scaffold provided by a bilayer type I-III collagen membrane.

Methods. From December 1999 to January 2001, 13 patients underwent implantation procedure for deep cartilage defects. Age of patients ranged from 18 to 49 years (mean age, 35 years). The mean defect size was 3.5 cm^sup 2^ (range, 2.0-4.5 cm^sup 2^). Clinical and functional evaluation were performed using various score systems for the ankle and the knee, and magnetic resonance imaging was performed at 6 and 12 months postoperatively. Membrane structure and cellular population were investigated by light microscopy, scanning electron microscopy, and electrophoresis before implantation.

Results. The mean follow-up was 6.5 months (range, 2-15 months). No complications were observed in the postoperative period. The 6 patients with a minimum follow-up of 6 months showed an improvement in clinical and functional status after surgery. Magnetic resonance images showed the presence of hyaline-like cartilage at the site of implantation; there was evidence of chondroblasts and type II collagen inside the seeded membrane.

Conclusion. Matrix-induced autologous chondrocyte implantation offers several advantages with respect to the traditional cultured cell procedure. These include technical simplicity, short operating time, minimal invasiveness, and easier access to difficult sites. It appears to be a reliable method for the repair of deep cartilage defects.

Key words: chondral defect; chondrocytes; tissue engineering

INTRODUCTION

During the past decade, interest in the management of cartilage lesions has grown owing to the introduction of new therapeutic options. Autologous chondrocyte implantation is a well-established procedure for the treatment of large, full-thickness chondral defects of different joints. Its main field of application is the knee, with the first clinical experience reported in 1987.1

It has been shown that autologous chondrocyte implantation can lead to the formation of hyaline-like cartilage in sites of repair; this represents a significant advantage with respect to conventional techniques relying on the repair potential of bone marrow, such as abrasions, drilling, and microfractures.2-5 Moreover, autologous chondrocyte implantation can overcome the limits of more recent techniques-namely, mosaicplasty-for the treatment of large chondral lesions, where dead spaces between grafts are filled with fibrocartilage and surface irregularities can be present.6 In the autologous chondrocyte implantation technique, a suspension culture of autologous chondrocytes is injected into the defect, which is previously covered with a periosteal patch; satisfactory medium- and long-term clinical results have been achieved.2-4,7

Matrix-induced autologous chondrocyte implantation (MACI; Verigen, Leverkusen, Germany) can be considered an evolution of conventional autologous chondrocyte implantation. It is a tissue-engineering technique that requires the use of a type I-III bilayer membrane of collagen seeded with cultured autologous chondrocytes. MACI has been adopted at the Institute of Orthopaedics and Traumatology, University of Insubria, Italy since December 1999. This study reports the results of using MACI on 6 patients, with a minimum follow-up of 6 months.

MATERIALS AND METHODS

The first surgical step was the arthroscopic assessment of the joint and the harvesting of articular cartilage (5 mm x 10 mm) from a non-weightbearing area of the knee. In our series of patients, all biopsies were performed at the superior medial edge of the femoral trochlea. The biopsy material was immediately placed in a nutrient medium tube and forwarded to a cell laboratory (Verigen, Germany), along with 100 ml of autologous blood, distributed in 10 tubes. An enzymatic process that separates the chondrocytes from the matrix, and cell culture (using autologous serum and growth factors) over 3 to 4 weeks induced them to multiply to become about 15 to 20 million dedifferentiated cells. The cells were seeded on a type I-III collagen bilayer membrane and sent back to the hospital for the scheduled date of implantation.

The implant procedure was performed in a tourniquet-controlled bloodless field. In cases of knee lesions, the joint was approached through a small parapatellar skin incision and arthrotomy (Fig. 1a). For the ankle, osteotomy of the malleolus was usually performed to gain good exposure of the chondral defect. The softened borders of the defect were debrided without any bleeding of the subchondral bone plate. In cases of accidental bleeding, haemostasis was achieved by local application of epinephrine and thrombin.

By taking an impression, the outline of the defect was transferred to the seeded membrane, which was cut out with scissors (Fig. 1b). Using fibrin glue (Fig. 1c), the membrane was implanted in the defect and its stability was tested by making some movements of the joint (Fig. 1d). After wound closure, the joint was covered with a compressive elastic bandage. Continuous passive motion was started on the first postoperative day for the knee and on the third postoperative day for the ankle, achieving daily increases in range of motion. Isometric strengthening of the quadriceps began in the first week, while partial weightbearing was allowed after 2 months and full weightbearing shortly thereafter. Return to sports was related to the type of joint impact required by the specific activity: sports requiring low loading stresses on the knee (e.g. swimming and cycling) were allowed 3 months after surgery, while sport activities that required jumping, twisting, and running with quick stops and starts (e.g. soccer and basketball) were delayed for at least 10 months.