Autologous chondrocyte implantation

Autologous chondrocyte implantation (ACI, ATC code M09AX02 (WHO)) is a biomedical treatment that repairs damages in articular cartilage. ACI provides pain relief while at the same time slowing down the progression or considerably delaying partial or total joint replacement (knee replacement) surgery. The goal of ACI is to allow people suffering from articular cartilage damage to return to their old lifestyle; regaining mobility, going back to work and even practicing sports again.

ACI procedures aim to provide complete hyaline repair tissues for articular cartilage repair. Over the last 20 years, the procedure has become more widespread and it is currently probably the most developed articular cartilage repair technique.

The surgical technique was first performed in Sweden in 1987; the results of the 9 year follow up are available in Lars Peterson et al. 2000. Brittberg published the first description of the technique on humans in 1994. He reported good and promising results with 23 patients for defects on the femoral condyles (Brittberg et al., 1994).The technique also seems promising with regard to long-term results.[1]

Procedure

This cell based articular cartilage repair procedure takes place in three stages. In a first stage, between 200 and 300 milligrams cartilage is sampled arthroscopically from a less weight bearing area from either the intercondylar notch or the superior ridge of the medial or lateral femoral condyle of the patient. The matrix is removed enzymatically and the chondrocytes isolated. These cells are grown in vitro in a specialised laboratory for approximately four to six weeks, until there are enough cells to reimplant on the damaged area of the articular cartilage. The patient then undergoes a second treatment, in which the chondrocytes are applied on the damaged area during an open-knee surgery (also called arthrotomy). These autologous cells should adapt themselves to their new environment by forming new cartilage. During the implantation, chondrocytes are applied on the damaged area in combination with a membrane (tibial periosteum or biomembrane) or pre-seeded in a scaffold matrix.

ACI Complications

The occurrence of subsequent surgical procedures (SSPs), primarily arthroscopy, following ACI is common. For example, in the Study of the Treatment of Articular Repair (STAR), 49% of Carticel ACI patients underwent an SSP on the treated knee, during the 4-year follow up. The most common serious adverse events (up to 5% of patients), include arthrofibrosis and joint adhesions, graft overgrowth, chondromalacia or chondrosis, cartilage injury, graft complication, meniscal lesion, graft delamination, and osteoarthritis. Source: Carticel.

A recent study from Germany, published in the November 2008 issue of the American Journal of Sports Medicine, analyzed 349 ACI procedures of the knee joint. Three different ACI techniques were used. A major proportion of complications after ACI can be summarized by 4 major diagnoses: symptomatic hypertrophy, disturbed fusion, delamination, and graft failure. Among those, the overall complication rate and incidence of hypertrophy of the transplant were higher for periosteum-covered ACI. Furthermore, an increased rate of symptomatic hypertrophy was found for patellar defects. Source: Philipp Niemeyer, MD, et al.: Characteristic Complications After Autologous Chondrocyte Implantation for Cartilage Defects of the Knee Joint. The American Journal of Sports Medicine 36:2091-2099 (2008).

Randomized clinical studies

Knutsen and coworkers have published the 2-year[2] and 5-year[3] follow-up results after surgery in patients randomized for ACI or microfracture treatment of localized articular defects of the knee joint. At the two-year follow-up the authors concluded that: "Both methods had acceptable short-term clinical results. There was no significant difference in macroscopic or histological results between the two treatment groups and no association between the histological findings and the clinical outcome at the two-year time-point." At the five-year follow-up the conclusions were similar: "Both methods provided satisfactory results in 77% of the patients at five years. There was no significant difference in the clinical and radiographic results between the two treatment groups and no correlation between the histological findings and the clinical outcome. One-third of the patients had early radiographic signs of osteoarthritis five years after the surgery. Further long-term follow-up is needed to determine if one method is better than the other and to study the progression of osteoarthritis."

Saris et al. studied histologic results and clinical outcome in a similar randomized study and concluded that: "One year after treatment, characterized chondrocyte implantation was associated with a tissue regenerate that was superior to that after microfracture. Short-term clinical outcome was similar for both treatments. The superior structural outcome may result in improved long-term clinical benefit with characterized chondrocyte implantation. Long-term follow-up is needed to confirm these findings."[4]

At present it seems fair to conclude that the repair tissue formed by ACI is as good or possible slightly better than a less invasive and simpler surgical technique 1–2 years after the surgery. ACI has not yet been shown to give better clinical outcome than microfracture at short-term or medium-term follow-up.

Minas et al. studied clinical outcome in a cohort study of 321 patients. They found that defects treated by ACI, which had a prior treatment with marrow stimulating techniques, such as microfracture, were three times more likely to fail than for defects treated by ACI, which did not have a prior marrow stimulating technique. They concluded that marrow stimulating techniques should be employed judiciously in larger cartilage defects that may require future treatment with ACI.[5]

References

  1. ↑ Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L (October 1994). "Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation". N. Engl. J. Med. 331 (14): 889–95. doi:10.1056/NEJM199410063311401. PMID 8078550.
  2. ↑ Knutsen G, Engebretsen L, Ludvigsen TC, Drogset JO, Grøntvedt T, Solheim E, Strand T, Roberts S, Isaksen V, Johansen O (March 2004). "Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial". J Bone Joint Surg Am. 86–A (3): 455–64. PMID 14996869.
  3. ↑ Knutsen G, Drogset JO, Engebretsen L, et al. (October 2007). "A randomized trial comparing autologous chondrocyte implantation with microfracture. Findings at five years". J Bone Joint Surg Am. 89 (10): 2105–12. doi:10.2106/JBJS.G.00003. PMID 17908884.
  4. ↑ Saris DB, Vanlauwe J, Victor J, et al. (February 2008). "Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture". Am J Sports Med. 36 (2): 235–46. doi:10.1177/0363546507311095. PMID 18202295.
  5. ↑ Minas T, Gomoll AH, Rosenberger R, Royce RO, Bryant T (May 2009). "Increased failure rate of autologous chondrocyte implantation after previous treatment with marrow stimulation techniques". Am J Sports Med. 37 (5): 902–8. doi:10.1177/0363546508330137. PMID 19261905.

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