MACI vs. ACI: How the Third Generation ACI Repairs Knee Cartilage

While orthopedic surgeons have used autologous chondrocyte implantation (ACI) for decades, matrix-induced ACI (MACI) is the third and latest ACI generation to repair cartilage defects in the adult knee. What differentiates MACI from previous generations of ACI is its simplified, cutting-edge approach to chondrocyte delivery.

Knee cartilage regeneration before and after MACI

Effectiveness of MACI in joints other than the knee has not been established. Safety and effectiveness of MACI in patients over the age of 55 years have not been established.

Earlier Generations of ACI

Phase one of an ACI consists of an arthroscopy where a surgeon harvests cartilage cells, which are then treated and multiplied in a lab to form a new autologous cartilage implant. Phase two consists of implantation surgery.

The first two generations of ACI required longer, more complex implantation procedures. In implantation surgery for the first generation of ACI, a surgeon made two incisions. The first incision was to the knee and exposed the patient's cartilage damage, while the second was over the tibia and allowed the surgeon to harvest periosteum tissue. This tissue was used to shape a periosteal cover approximately the size of the patient's cartilage defect. The surgeon sutured the periosteal cover in place over the patient's cartilage defect to form a seal and inject the new chondrocytes under the cover. This procedure had variable success. The most common complication reported was periosteal hypertrophy (scar tissue) around the edge of periosteal cover.

The second generation of ACI, or collagen-covered ACI (CACI), used a biodegradable collagen membrane to implant cartilage cells rather than a periosteal cover. CACI avoided the drawbacks of the periosteal cover but had its own complications that resulted from suturing the collagen cover. This included surgical complexity, microtrauma to tissue and cell leakage.

How is MACI Different?

MACI, the latest advancement in ACI, delivers cells via a resorbable type I/III porcine collagen membrane that makes surgical implantation easier for surgeons. As opposed to the previous generations of ACI, the chondrocytes are applied directly to the membrane during manufacturing, simplifying the implantation process. During implantation, MACI's durable membrane is secured in place with fibrin glue rather than time-intensive and cumbersome sutures. This means the surgeon can deliver the implant with smaller incisions during a shorter, less invasive procedure. The MACI membrane's versatility means that it can be used to treat defects in multiple areas of the knee and more difficult to treat defects, including uncontained defects. Previous ACIs were limited in their indication for the treatment of cartilage defects.

The most frequently occurring adverse reactions reported for MACI (≥5%) were arthralgia, tendonitis, back pain, joint swelling, and joint effusion. Serious adverse reactions reported for MACI were arthralgia, cartilage injury, meniscus injury, treatment failure, and osteoarthritis. Please see full ISI and link to PI below.

During manufacturing, characterized cells are distributed onto the membrane using Vericel's proprietary Uniform Loading Unit (ULU), which allows for a uniform delivery of cells to cartilage defects, regardless of defect size and shape. It is dual-sided; a porous side allows cell attachment, and a smooth side aids joint articulation. This membrane can be sized to fit the exact shape and dimensions of the patient's cartilage membrane. Plus, the implant is resilient and strong; it permits sutures or suture anchor fixation when needed.

MACI Manufacturing

This MACI membrane is aseptically manufactured at Vericel's FDA-licensed facility. Before each procedure, rigorous assay testing is done to certify the implant's viability, identity and potency prior to product release. Following manufacturing, physicians may use a MACI implantation tray to shape the membrane to fit the patient's cartilage defect.


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Please see below for full indication and ISI.