Description

Articular Cartilage Lesions

Damaged articular cartilage typically fails to heal on its own and can be associated with pain, loss of function, and disability, and may lead to debilitating osteoarthritis over time. These manifestations can severely impair an individual’s activities of daily living and adversely affect quality of life.

Treatment

Conventional treatment options include débridement, subchondral drilling, microfracture, and abrasion arthroplasty. Débridement involves the removal of synovial membrane, osteophytes, loose articular debris, diseased cartilage, and is capable of producing symptomatic relief. Subchondral drilling, microfracture, and abrasion arthroplasty attempt to restore the articular surface by inducing the growth of fibrocartilage into the chondral defect. Compared with the original hyaline cartilage, fibrocartilage has less capability to withstand shock or shearing force and can degenerate over time, often resulting in the return of clinical symptoms. Osteochondral grafts and autologous chondrocyte implantation (ACI) attempt to regenerate hyaline-like cartilage and thereby restore durable function.

With ACI, a region of healthy articular cartilage is identified and biopsied through arthroscopy. The tissue is sent to a facility licensed by the U.S. Food and Drug Administration (FDA) where it is minced and enzymatically digested, and the chondrocytes are separated by filtration. The isolated chondrocytes are cultured for 11 to 21 days to expand the cell population, tested, and then shipped back for implantation. With the individual under general anesthesia, an arthrotomy is performed, and the chondral lesion is excised up to the normal surrounding cartilage. Methods to improve the first-generation ACI procedure have been developed, including the use of a scaffold or matrix-induced autologous chondrocyte implantation (MACI) composed of biocompatible carbohydrates, protein polymers, or synthetics. The only FDA-approved MACI product to date is supplied in a sheet, which is cut to size and fixed with fibrin glue. This procedure is considered technically easier and less time-consuming than the first-generation technique, which required suturing of a periosteal or collagen patch and injection of chondrocytes under the patch.

Desired features of articular cartilage repair procedures are the ability (1) to be implanted easily, (2) to reduce surgical morbidity, (3) not to require harvesting of other tissues, (4) to enhance cell proliferation and maturation, (5) to maintain the phenotype, and (6) to integrate with the surrounding articular tissue. In addition to the potential to improve the formation and distribution of hyaline cartilage, use of a scaffold with MACIeliminates the need for harvesting and suture of a periosteal or collagen patch. A scaffold without cells may also support chondrocyte growth.

Regulatory Status

The culturing of chondrocytes is considered by the FDA to fall into the category of manipulated autologous structural cells, which are subject to a biologic licensing requirement. In 1997, Carticel® (Genzyme; now Vericel) received the FDA approval for the repair of clinically significant, “...symptomatic cartilaginous defects of the femoral condyle (medial lateral or trochlear) caused by acute or repetitive trauma.…”

In December 2016, MACI® (Vericel) received the FDA approved for “the repair of symptomatic, single or multiple full-thickness cartilage defects of the knee with or without bone involvement in adults.” MACI® consists of autologous chondrocytes that are cultured onto a bioresorbable porcine-derived collagen membrane. In 2017, production of Carticel® was phased out, and MACI® is the only ACI product available in the U. S.

A number of other second-generation methods for implanting autologous chondrocytes in a biodegradable matrix are currently in development or testing or are available outside of the U. S. They include Atelocollagen (Koken), a collagen gel; Bioseed® C (BioTissue Technologies), a polymer scaffold; CaReS (Ars Arthro), collagen gel; Cartilix (Biomet), a polymer hydrogel; Chondron (Sewon Cellontech), a fibrin gel; Hyalograft C (Fidia Advanced Polymers), a hyaluronic acid-based scaffold; NeoCart (Histogenics), an ACI with a 3-dimensional chondromatrix in a phase 3 trial; and Novocart®3D (Aesculap Biologics), a collagen-chondroitin sulfate scaffold in a phase 3 trial. ChondroCelect® (TiGenix), characterized as a chondrocyte implantation with a completed phase 3 trial, uses a gene marker profile to determine in vivo cartilage-forming potential and thereby optimizes the phenotype (e.g., hyaline cartilage vs fibrocartilage) of the tissue produced with each ACI cell batch. Each batch of chondrocytes is graded based on the quantitative gene expression of a selection of positive and negative markers for hyaline cartilage formation. Both Hyalograft C and ChondroCelect® have been withdrawn from the market in Europe.

Criteria

Autologous chondrocyte implantation may be considered medically necessary for the treatment of disabling full-thickness articular cartilage defects of the knee caused by acute or repetitive trauma when all of the following criteria are met:

• Adolescent individuals should be skeletally mature with documented closure of growth plates (e.g., ≥15 years)
• Adult individuals should be too young to be considered an appropriate candidate for total knee arthroplasty or other reconstructive knee surgery (e.g., <55 years) 
• Focal, full-thickness (grade III or IV) unipolar lesions of the weight-bearing surface of the femoral condyles, trochlea, or patella at least 1.5 cm² in size
• Documented minimal to absent degenerative changes in the surrounding articular cartilage (Outerbridge grade II or less), and normal-appearing hyaline cartilage surrounding the border of the defect
• Normal knee biomechanics or alignment and stability achieved concurrently with autologous chondrocyte implantation

Autologous chondrocyte implantation for all other joints, including the talar, and any indications other than those listed above is considered investigational.

Procedure Codes

Diagnosis Codes

Professional Statements and Societal Positions Guidelines

Practice Guidelines and Position Statements

American Academy of Orthopaedic Surgeons

In guidelines on the diagnosis and treatment of osteochondritis dissecans, the American Academy of Orthopaedic Surgeons (2010) did not recommend for or against a specific cartilage repair technique in symptomatic skeletally immature or mature individualswith an unsalvageable osteochondritis dissecans lesion. This finding of insufficient evidence was based on a systematic review that found four level IV studies addressing cartilage repair techniques for an unsalvageable osteochondritis dissecans lesion. Because each level IV articles used different techniques, different outcome measures, and differing lengths of follow-up, the Academy deemed the evidence for any specific technique inconclusive.

National Institute for Health and Care Excellence

The National Institute for Health and Care Excellence (2018) updated its 2005 guidance on the use of autologous chondrocyte implantation. The Institute"… as an option for treating symptomatic articular cartilage defects of the femoral condyle and patella of theknee (International Cartilage Repair Society grade III or IV) in adults, only if:

• the person has not had previous surgery to repair articular cartilage defects;
• there is minimal osteoarthritic damage to the knee (as assessed by clinicians experienced in investigating knee cartilage damage using a validated measure for knee osteoarthritis); and
• the defect is over 2 cm²."

Links

S-5048-01

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