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March 12, 2024
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BLOG: Matrix-induced autologous chondrocyte implantation for osteochondral defects

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Osteochondral defects of the knee articular cartilage are injuries frequently seen in orthopedics and sports medicine.

The author’s previous experience with patients with osteochondral defects (OCD) includes assisting chondroplasty and microfracture or osteochondral autograft transplant (OAT) procedures.

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Matrix-induced autologous chondrocyte implantation may be considered for osteochondral defects. Image: Adobe Stock

Newer surgical techniques utilize autologous chondrocyte implantation (ACI). There are two procedures: harvesting autologous chondral cartilage from a non-weight-bearing surface of the knee and sending the biopsy sample to a lab to grow new cells; and a procedure for reimplanting (gluing not suturing) the new cells into the OCD.

This blog is a review of OCD of the knee and various treatment options with a focus on matrix-induced ACI (MACI).

– Sam Dyer, PA-C, President, Physician Assistants in Orthopaedic Surgery

Osteochondral defects of the knee are lesions in the articular cartilage that commonly occur due to trauma or underlying tissue disorders. Articular cartilage plays a crucial role in knee joint preservation due to its specialized cellular organization and function.

Rachel Greene
Rachel Greene

Many joint-restoring techniques aim to reduce symptoms and the need for future arthroplasty, but available data are inconclusive about the effectiveness of these interventions due to the lack of longitudinal studies. Some of the most promising techniques include cartilage regeneration using autologous cells.

This blog provides an overview of MACI as treatment for symptomatic OCD and emphasizes the need for research analyzing long-term outcomes of patients.

Pathogenesis and prevalence

Osteochondral defects, or articular cartilage defects, can progressively degrade the knee joint due to repeated trauma or inflammatory disease. Articular cartilage is specialized connective tissue that minimizes friction to allow for smooth articulation and helps to absorb and distribute forces throughout the knee. Without a smooth articular surface, underlying bone becomes exposed which can cause bone spurs, sclerosis and narrowing of joint space. These irreversible changes typically lead to pain, stiffness and decreased function for patients. Once the damage reaches end-stage (ie, severe osteoarthritis), the only cure is arthroplasty.

The prevalence of OCD in the general U.S. population has been reported at 12%. It is not well understood which patients with osteochondral defects will progress to OA, although there is some evidence that more severe defects are correlated with worse outcomes. The CDC reports OA affects more than 32.5 million U.S. adults and is a leading cause of disability in the United States.

Treatment course

Determining a treatment route should be guided by shared decision-making between the

patient and the provider. Managing patients with articular cartilage defects is challenging due to the unique properties of articular cartilage. It lacks blood flow, lymphatic drainage and metabolism, which cumulatively limit the ability of the tissue to heal.

Conservative management primarily includes activity modification, physiotherapy and

pain management. However, these options are often insufficient for larger lesions and evidence of their efficacy varies widely. Common surgical options include OAT procedure, autologous matrix-induced chondrogenesis (AMIC) and ACI. There is a developing role for the different types of cartilage salvation; however, this article focused on MACI.

MACI received FDA approval in 2016 for symptomatic full-thickness OCD of the knee. To qualify for the MACI procedure, patients must meet inclusion criteria such as confirming defect on MRI.

There are no specified size qualifications for the defect, and patients with multiple lesions can qualify. The procedure involves two separate surgeries, several weeks apart. First, an orthopedic surgeon performs a knee arthroscopy with a biopsy of articular cartilage from a non-weight-bearing area of the knee joint, such as the femoral notch. The biopsy is sent to a cell processing lab to grow autologous chondrocytes on a collagen matrix for several weeks.

At the start of the second surgery, the collagen matrix implant, infused with autologous chondrocytes, is cut and shaped to be the exact size of the defect. Then, the collagen membrane is glued directly into the osteochondral defect.

Compared with past generations of ACI, the primary improvement of MACI is it glues, rather than sutures, the implant to the defect. Gluing the implant theoretically causes less surrounding tissue damage and allows for a more exact match to the defect, compared with suturing. Recent studies show both techniques are safe and effective, with MACI yielding superior outcome scores at 2 and 5 years postoperatively.

Outcomes

Patients who underwent MACI experienced significant KOOS improvements at 2 years postoperatively. On average, scores regarding activities of daily living improved 44 points (on a 0-100 scale) and scores regarding knee-related quality of life improved 38 points (on a 0-100 scale) after 2 years. The most common adverse events in MACI clinical trials for FDA approval were treatment failure, arthralgia and joint swelling with 34.7% of participants reporting one of these during a 2-year period. A meta-analysis of 1,000 patients who underwent MACI reported arthralgia as the most common adverse event with a prevalence of 0.8% and that treatment failure occurred in 0.003% of participants, although this study was based on lower-level evidence.

An educational review of treatments for OCD recommends MACI as the best intervention regarding efficacy and safety, followed by OAT. No randomized control trials have been conducted on AMIC or OCA, so outcomes cannot be directly compared with MACI. Current research demonstrates a clear benefit of MACI compared with microfracture, and available comparison studies between MACI and other cartilage regeneration techniques demonstrate comparable and inconclusive outcomes that warrant further investigation.

Conclusion

The variety of options for treating OCD demonstrates the challenge of regenerating quality articular cartilage. While some expect MACI to become the preferred approach due to its reduced intraoperative time, reduced invasiveness, surgical simplicity and reproducibility, more research is needed to assess the potential of MACI to meet this prediction. More specifically, areas in need of high-level, longitudinal evidence include comparisons between MACI and alternative treatments, outcomes of MACI past 5 years postoperatively, including effects on OA risk, and postoperative protocols for patients who undergo MACI.

Physician assistants in orthopedics have unique insight into the complexities of knee joint health and are the pioneers for advancing new technologies. Continuing research on articular cartilage, MACI and other cartilage regeneration technologies will be vital to equipping physician assistants and other orthopedic practitioners with the knowledge and tools they need to help improve patients’ lives.

References:

Basad E, et al. Knee Surg Sports Traumatol Arthrosc. 2010;doi:10.1007/s00167-009-1028-1.

Carey JL, et al Orthop J Sports Med. 2020;doi:10.1177/2325967120941816.

Howell M, et al. Curr Rev Musculoskelet Med. 2021;doi:10.1007/s12178-020-09685-1.

Osteoarthritis 2020 CDC. Available at:

https://www.cdc.gov/arthritis/basics/osteoarthritis.htm.

Saris D, et al. Am J Sports Med. 2014;doi:10.1177/0363546514528093.

Sophia Fox AJ, et al. Sports Health. 2009;doi:10.1177/1941738109350438.

Tamaddon M, et al. Biodes Manuf. 2018;doi:10.1007/s42242-018-0015-0.

Vijayan S, et al. Indian J Orthop. 2010;doi:10.4103/0019-5413.65136.

Sources/Disclosures

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Disclosures: Greene reports no relevant financial disclosures.