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Important Risk Factors for Treatment Failure with ACI

Physicians use knowledge of risk factors to assess which patients might respond best to each treatment approach available for many problems. In this study, German surgeons take a closer look at factors that might increase the risk of revision surgery after autologous chondrocyte implantation or ACI.

ACI is a cell-therapy approach to treat deep or large defects in the knee joint cartilage. It involves using cartilage cells (chondrocytes) to help regenerate articular (joint surface) cartilage. Studies show that in about one-fifth of patients who have this treatment, there is a failure of the cartilage cells to regenerate and fill in the hole.

In cases of treatment failure, a second (revision) surgery is required. Surgeons would like to spare patients both the failed results and the need for more surgery. Identifying risk factors that could increase the likelihood of treatment failure would be helpful. Surgeons could screen patients before surgery and perhaps choose a different treatment approach if it looks like there are indicators that autologous chondrocyte implantation (ACI) might fail.

To conduct this study, 413 patients who had the first ACI procedure for a full-thickness defect (down to the bone) were followed. Anyone who had a failed response was examined more carefully. Data collected about patients with failed outcomes was analyzed.

The kinds of information collected included age, sex (male or female), type of defect (size, location), body mass index (BMI, a measure of obesity), smoking history, and number of previous knee injuries or surgeries. Follow-up was a minimum of at least two years. Some patients were followed for up to 11 years.

Criteria for a second surgery included continued knee pain, loss of knee function, and MRI evidence of pathology. Patients with other knee injuries (e.g., ruptured ligaments, torn meniscus) were not included so there would be no confusion about who had a true failed implantation and who had other causes of knee pain.

Just about one-fifth of the group (21.3 per cent) needed revision surgery. They didn't all have the same exact problem. Problems ranged from too much cartilage regrowth (called transplant hypertrophy) to not enough (insufficient regeneration). In some cases, there were loose pieces of cartilage in the joint space or bone cysts that formed.

The factors that were most significant for failed ACI included being female, having a previous bone marrow treatment, the use of a periosteum patch to cover the ACI, and previous knee surgery (or surgeries) on that knee. There was no apparent link between age, smoking history, body size, or defect size or location.

A periosteal patch is a thin layer of bone harvested from a nonweight-bearing portion of the knee joint used to cover the implanted cartilage cells. It's a bit like placing a manhole cover over an open hole. It protects the healing lesion that has been filled with chondrocytes (cartilage cells).

Whenever possible, minimally invasive arthroscopic surgery was done to address the problem. Sometimes the surgeon just had to clean out the area of any bits of debris, bone, or excess cartilage. This procedure is called debridement. In some cases, the surgeon opted for a different surgical approach rather than revise or repeat the chondrocyte implantation.

What conclusions did the researchers come to from this study? The four factors identified can be easily evaluated in patients before considering autologous chondrocyte implantation (ACI) as the treatment of choice for cartilage defects. These factors should be included in the decision-making process and determination of prognosis.

Two recommendations were made regarding the surgical procedure itself. First, whenever possible, contributing knee problems (e.g., ligament instability, boney malalignment) should be treated along with the ACI procedure. And second, making sure the transplanted cartilage is attached to nearby healthy cartilage might help.

The issue of nicotine use may require additional study. Past research results have linked nicotine with greater risk of developing cartilage defects and delayed healing. Nicotine appears to have a toxic effect on chondrocytes (cartilage cells) and may contribute to the formation of holes and defects in the cartilage. The role of nicotine in failed chondrocyte transplantation was not obvious in this study.


Pia M. Jungmann, MD, et al. Autologous Chondrocyte Implantation for Treatment of Cartilage Defects of the Knee. What Predicts the Need for Reintervention? In The American Journal of Sports Medicine. January 2012. Vol. 40. No. 1. Pp. 58-67.

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*Disclaimer:* The information contained herein is compiled from a variety of sources. It may not be complete or timely. It does not cover all diseases, physical conditions, ailments or treatments. The information should NOT be used in place of visit with your healthcare provider, nor should you disregard the advice of your health care provider because of any information you read in this topic.
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