Matrix-assisted autologous chondrocyte implantation in the knee

Overview

Chapter synopsis

MACI (autologous cultured chondrocytes on porcine membrane) is indicated for symptomatic full-thickness chondral defects of the knee in patients 18–55 years of age. Although diagnostic imaging and clinical examination are important, arthroscopic assessment provides the final confirmation of the appropriateness of this two-staged, surface-based treatment for cartilage restoration. A chondral biopsy is performed to obtain healthy autologous cartilage to grow sufficient cells for reimplantation at the open second stage of the cell implantation technique. Postoperative rehabilitation allows for protection and stimulation of the maturing chondrocytes, ensuring the best opportunity for return to improved symptom-free function.

Important points

Indications

Symptomatic, predominantly full-thickness chondral defects (grade III to IV lesions) and osteochondritis dissecans lesions of the knee, including the femoral condyles, patella, trochlea, and in rare circumstances, the tibial plateau
Medium to large focal lesions, typically larger than 2 cm ²

Contraindications

Advanced or diffuse osteoarthritis
Diffuse, bipolar, sclerotic, or bone-on-bone cartilage lesions
Inflammatory arthropathy
Uncorrected malalignment, meniscal insufficiency, or ligamentous instability
Inability to comply with rehabilitation protocol
Hypersensitivity to bovine or porcine products

Symptoms of chondral defects

Pain with weight bearing or increased loading
Pain with stairs or getting into and out of a chair for patellofemoral defects
Complaints of mechanical symptoms such as locking, catching, or giving way; point tenderness in the involved area
Recurrent swelling or effusion

Surgical technique highlights

Chondral biopsy is required initially for the autologous chondrocytes to be cultured and expanded for reimplantation
MACI is an open procedure requiring adequate exposure for preparation and implantation
The defect is prepared by sharply demarcating the edge of the defect to vertical margins and removing all degenerated cartilage remnants down through the calcified cartilage layer without violating the subchondral plate.
The defect is sized by making a template and transferring the size and shape to the covering matrix membrane of absorbable type I/III collagen membrane with applied cultured autologous chondrocytes. Alternatively, depending on the size characteristics of the defect, custom geometric cutting guides may be utilized for defect and membrane preparation.
The inset membrane is affixed to the subchondral bone and defect perimeter with fibrin glue.
Continuous passive motion is an early key component of an extensive rehabilitation process that maximizes the maturation of the chondrocytes.

Clinical and surgical pearls

Adequate exposure is paramount to consistent defect preparation and matrix implantation.
Defects with uncontained edges may require alternate methods to securely attach the covering membrane, such as micro–suture anchors, trans-osseous drill holes, or soft tissue reapproximation.
Perform any concomitant procedures before completing the cell implantation, which should be the last portion of the procedure.
Ensure that the defect is sharply demarcated back to a rim of the healthiest appearing remaining cartilage, thereby allowing a stable, firm edge to which the matrix may be securely adhered and protected from eccentric forces during early motion.

Clinical and surgical pitfalls

Paramount to biologic repair of an articular cartilage defect, is establishing the most ideal balanced intra-articular environment within the knee.
This requires that mechanical alignment, ligamentous stability, and meniscal function be optimally treated either before or concomitantly with MACI.
Multiple or multifocal defects can be treated with MACI at the same implantation.
Early emphasis on range of motion helps prevent the potential complication of flexion and/or extension contracture.
The use of the inlay type I/III collagen membrane seeded with autologous chondrocytes has greatly diminished the complication of mechanical symptoms and/or graft hypertrophy requiring arthroscopic debridement, seen in about 25% of cases when the patient’s periosteum was initially used as a covering membrane with first generation ACI.

Articular cartilage defects are often encountered during routine knee arthroscopy and may be frequently noted on magnetic resonance imaging (MRI) in young athletes. ^, When symptomatic, cartilage lesions can contribute to functional disability comparable to that seen in advanced knee osteoarthritis. Despite the prevalence of articular cartilage injury, traditional methods for treatment and repair, such as chondroplasty or marrow stimulation, have not resulted in favorable long-term results. However, in 1994, Brittberg and colleagues first developed and described a technique for autologous chondrocyte implantation (ACI), which has since gained a major role in the treatment of large full-thickness chondral injuries. Contemporary outcomes are now available at over 20 years of clinical follow-up, and more than 75% of the patients have demonstrated improvement with relatively minor complications. Expanded indications further demonstrated that over 80% of patients had good-to-excellent, self-reported outcomes with patella and bipolar patellofemoral lesions with concomitant attention to optimizing patellofemoral biomechanics. ^, Additionally, very large lesions were shown to have good-to-excellent outcomes with proactive management of knee kinematics. In the ACI technique, a small biopsy specimen of healthy articular cartilage is obtained arthroscopically, then the native cartilage is allowed to undergo in vitro chondrocyte amplification in cell culture, returning autologous chondrocyte cells available for implantation into the defect at the second stage of the regeneration procedure. The rationale for use of autologous chondrocytes is to produce a repair issue that more closely resembles the morphologic characteristics of the type II hyaline cartilage, allowing greater durability and natural function of the knee joint.

As clinical experience with ACI expanded around the world, research continued to advance the surgical procedure and reduce unsatisfactory outcomes of technique-related complications. The incidence of 15% to 26% of patients with periosteal graft hypertrophy was noted to be reduced to less than 2.5% with use of a collagen membrane to contain the chondrocytes. As cell culturing methods progressed, the autologous chondrocytes were then able to be applied more uniformly into the collagen membrane and fixed to the bony bed to a defect with fibrin glue rather than employing tedious suturing. Further substantiation of the MACI technique (“third generation ACI”) came from the international multi-center prospective randomized study of matrix-applied autologous chondrocyte implantation (MACI) versus microfracture for defects with an average size of 4.8 cm ² , which showed clinically significant improvement over microfracture at 2 years. Subsequent 5-year follow-up of the same cohort furthermore concluded that MACI-treated symptomatic cartilage knee lesions were clinically and significantly improved compared to microfracture. In 2016, the United States Federal Drug Administration (FDA) approved MACI (autologous cultured chondrocytes on porcine collagen membrane) for repair of symptomatic, single or multiple full-thickness cartilage defects of the knee, to include the femoral condyles, trochlea, patella and tibial plateau in adults.

Preoperative considerations

History and clinical presentation

A thorough history is the initial step in determining whether MACI is the appropriate treatment for a suspected chondral defect. Patients with femoral condylar lesions commonly have pain with weight bearing or increased loading, and mechanical symptoms such as catching, locking, or giving way, and intermittent swelling or effusion are also common complaints. Patients often localize a specific area of pain or tenderness as well. The presence of a patellofemoral defect will produce similar complaints as well as anterior knee pain, with symptoms exacerbated by stairs, prolonged seating (i.e., movie theater sign), getting into and out of a chair or car. Patellar maltracking or instability symptoms may also be present, so it is prudent to match the patient’s complaints to the location of the chondral defect and determine if symptoms are originating from the defect or another coexisting pathology. Finally, individual patient characteristics must be considered during evaluation and treatment planning, and these may include age, body mass index (BMI), concomitant knee pathology, smoking, compliance, and functional expectations. With known chondral defects, additional information is frequently available through previous operative reports, clinical documentation, and intraoperative images. This will yield valuable information regarding the size, location, and number of defects present within the knee, and these factors must be considered to assess suitability of the defect for MACI.

Physical examination

Physical examination is helpful to correlate the patient’s presenting symptoms with the corresponding location of the chondral or osteochondral defect. A thorough assessment of the knee can quickly establish the presence of an effusion, particularly with ballottement of the suprapatellar pouch, and focal tenderness of the tibiofemoral or patellofemoral joint line. Range of motion deficits should be identified, and ligamentous stability, provocative meniscal findings, and dynamic patellofemoral maltracking are evaluated. Basic observation of gait and scrutiny of both coronal plane and rotation malalignment should be conducted, as this may also offer relevant information about the patient’s level of function.

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here