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Failed Autologous Chondrocyte Implantation

Complete Atraumatic Graft Delamination after Two Years. Full-thickness chondral injuries occur with an incidence between 5% and 10% in knee injuries with acute hemarthrosis

T. Muellner1, 2, A. Knopp1, T.C. Ludvigsen1, L. Engebretsen1

1 Department of Orthopaedic Surgery, Ulleval Hospital and Oslo University, Kirkeveien 166, 0407 Oslo, Norway

2 Univ. Clinic of Traumatology, University of Vienna Medical School, Waehringerguertel 18-20, A-1090 Vienna, Austria

 

Introduction

Full-thickness chondral injuries occur with an incidence between 5% and 10% in knee injuries with acute hemarthrosis.16 Due to subsequent pain and decreased function, as well as chondral lesions often progress to osteoarthritis, cartilage repair procedures have become common and the cartilage repair techniques have been intensively investigated.13 Many factors contribute to the treatment approach of symptomatic unipolar full thickness chondral lesions, and each cartilage repair technique has its own reported complications.14 Reports about complications after autologous chondrocyte implantation (ACI) are rare and usually occur in the first 8 months postoperatively. Minas T.14 found a rate of 37% complications (26 out of 70) that required surgery. Beside loss of range of motion in the early phase, later interventions were for catching symptoms with pain and effusion, which developed as a result of periostal hypertrophy. A failure rate of 7% (5 out of 70) occurred due to falls in the recovery in 3 patients and due to adhesions to the graft in multiply transplanted knees in 2 patients.14 

However, to the authors´ present knowledge, there are no reports available about an atraumatic complete graft delamination occuring 2 years after ACI. We report one patient, who had complete resolution of his complaints even during strenuous activities after an ACI and was admitted to the hospital with a locked knee 2 years after the ACI.

Case Report

In 1997, a 42 years old man had a bicycle accident. He fell on his right knee and was admitted to the orthopaedic outpatient clinic. Radiographs showed no fracture and on clinical examination he presented symptoms of a lateral meniscal tear. Asked if he had previous knee problems, the patient claimed that for the last approximately 6 months a slowly increasing knee pain stopped him from strenuous cross-country-skiing, long-distance-running, or bicycling. The patient underwent arthroscopical surgery that revealed intact menisci but a full-thickness cartilage defect on the lateral femoral condyle. The defect measured twenty-five by twenty-five millimeters. The defect was arthroscopically debrided using a shaver and cartilage biopsy was obtained from the outer edge of the superior medial femoral condyle. Approximately 200 to 300 mg of healthy cartilage was harvested and then placed in the biopsy vial and sent to Genzyme (Genzyme Tissue Repair, Cambridge, MA). Clinically the patient did not improve and four months later an autologous chondrocyte implantation (ACI) was performed. The defect was exposured using a lateral arthrotomy. The chondral defect was first debrided circumferentially back to a healthy rim of surrounding articular cartilage with careful attention to avoid violating the subchondral bone. A periosteum patch was obtained from the proximal tibia and placed over the defect with the camium layer down to the bone. Multiple interrupted 6-0 absorbable sutures (Vicryl®, Ethicon, Summerville) secured the patch in place and fibrin glue further sealed the suture line. After injecting the autologous chondrocytes, the small remaining opening was closed with two sutures. After was hemostasis achieved the wound was closed in layers. The patient was set on a well-controlled gradual and progressive rehabilitation program, emphasizing continuous passive motion and non weight bearing for 6 weeks. During the first six months, the patient gradually improved. He had less pain, but sometimes crepitations and effusions occurred. A MRI investigation showed normal cartilage repair six months after the ACI (Figure 1).

One year after the ACI, the patient improved significantly and started to increase his physical activities. 14 months after the ACI the patient reached his former level of activity which included participation in the Birke Beiner and Vasa cross-country skiing races (56 km and 90 km, respectively). MRI showed normal cartilage signals and subchondral edema in the lateral femoral condyle (Figure 2). In October 1999 the patient was seen again at the orthopaedic outpatient clinic with a locked knee after an evening of strenous dancing. He described the sensation of a loose body in the suprapatellar pouch. MRI showed a loose body in the suprapatellar pouch and at the place of the former ACI again a cartilage defect could be seen. During arthroscopic evaluation the clinical diagnosis of a cartilage delamination was confirmed, and using an arthrotomy the cartilage defect was treated with osteochondral grafting, in a technique previously described by Hangody et al10, 11 six 6.5mm and three 4.5mm measuring grafts were obtained from the outer edges of the superior femoral condyles and around the intercondylar notch (Figure 3, Figure 4). The wound was closed in layers. Continuous passive motion was begun the first postoperative day, and partial weight-bearing was allowed with 10kg for 2 weeks, and in the following 8 weeks with 30kg. Thirteen weeks after the last operation the patient started to work as a male nurse again. He had no effusions, a free range of motion, still a difference in the thigh circumference of 4 cm. In March 2000 he started cross country ski training again and was able to ski approximately 35 km without problems.

A biopsy taken from normal appearing hyaline cartilage (Figure 5A) and the delaminated cartilage (Figure 5B) were sent for histological examination The specimen were fixeded in 4% formaldehyde solution, embedded in paraffin, further decalcified, and 5 µm-thick sections were prepared. After staining with hematoxylin-eosin (HE) the sections were examined under light microscopy. The delaminated cartilage showed a more or less wavy, irregular orientation of the collagen fibres, and few cells, mainly fibrocytes. The inner zone was calcified and contained chondrocytes without a normal nuclear structure. Compared to the normal cartilage, no specific zones could be identified.

Discussion

Articular cartilage exhibits little intrinsic capacity to heal after injury. 4 Already in 1743, Hunter stated that ”ulcerated cartilage is a troublesome thing, once destroyed is not repaired.”8 Since then a great number of investigations have been performed on the potential of the cartilage to restore itself, and a number of procedures have been used to take advantage of this potential.2, 3, 5, 9 Recently, arthroscopic techniques employing delivery of pluripotential marrow stem cells to the articular cartilage, have become very popular. These techniques were originally performed during open surgery.6, 18 To avoid tissue damage due to heat caused by drilling, Steadman and associates have introduced the microfracture technique where an arthroscopic awl is used to make multiple holes or ”microfractures” in the subchondral bone plate.19 While Akizuki and associates1 did not find an improvement of the clinical results, despite the presence of repair tissue, in osteoarthritic knees with eburnation after abrasion arthroplasty, Friedman and associates7 reported on an overall improvement of 60% following abrasion arthroplasty. Steadman and associates20 reported on pain relief in 75% of their young and active patients after microfracture at 3 to 5 years. In another study autologous perichondrium grafts in the treatment of full-thickness chondral defects in the knee was noted to provide a significant clinical improvement up to 2 years after transplantation.12 However, calcific radiodensity occured after 2 years in 21 of 30 patients implanted. Minas and Nehrer15 reported on the failure of 7 of 10 patients transplanted. The use of periostium alone showed early promise, but according to Minas, the long-term results have been disappointing both for the weightbearing femoral condyles and for the patella.14 

ACI has been shown to achieve clinical improvement in 92% of patients treated isolated weightbearing femoral condyle lesions in a 2- to 9-year follow-up.17 Minas reported on a 7% failure rate (5 patients) in his first 70 patients.14 However, the rate of complications requiring additional surgical intervention was 37% (26 out of 70 patients). These complications occured in the first 8 months postoperatively. To the authors present knowledge, there are no reports of a complete graft delamination which occurred 2 years after ACI. After ACI, the patient reported about complete recovery and was able to participate again in strenuous activities e.g. competitive cross-country skiing. Mosaicplasty was chosen as the second treatment option for our patient, although the defect was large, and worked well at least for the first six months.

Acknowledgements

Supported by a grant of the Austrian Society for Surgery and by the Austrian Society for Sports Medicine. No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

References

1.         Akizuki S, Yasukawa Y, Takizawa T: Does arthroscopic abrasion arthroplasty promote cartilage regeneration in osteoarthritic knees with eburnation? A prospective study of high tibial osteotomy with abrasion arthroplasty versus high tibial osteotomy alone. Arthroscopy 13: 9-17, 1997

2.         Brittberg M, Lindahl A, Nilsson A, et al.: Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 331: 889-95, 1994

3.         Brittberg M, Nilsson A, Lindahl A, et al.: Rabbit articular cartilage defects treated with autologous cultured chondrocytes. Clin Orthop, 326: 270-83, 1996

4.         Buckwalter JA, Mankin HJ: Articular cartilage. Part II: Degeneration and osteoarthrosis, repair, regeneration, and transplantation. J Bone Joint Surg 79, Am: 612-32, 1997

5.         Chu CR, Convery FR, Akeson WH, et al.: Articular cartilage transplantation. Clinical results in the knee. Clin Orthop, 360: 159-68, 1999

6.         Ficat RP, Ficat C, Gedeon P, et al.: Spongialization: a new treatment for diseased patellae. Clin Orthop, 144: 74-83, 1979

7.         Friedman MJ, Berasi CC, Fox JM, et al.: Preliminary results with abrasion arthroplasty in the osteoarthritic knee. Clin Orthop, 182: 200-5, 1984

8.         Goldberg VM, Caplan AI: Biologic restoration of articular surfaces. Instr Course Lect 48, 623-7, 1999

9.         Grande DA, Pitman MI, Peterson L, et al.: The repair of experimentally produced defects in rabbit articular cartilage by autologous chondrocyte transplantation. J Orthop Res 7: 208-18, 1989

10.       Hangody L, Kish G, Karpati Z, et al.: Arthroscopic autogenous osteochondral mosaicplasty for the treatment of femoral condylar articular defects. A preliminary report. Knee Surg Sports Traumatol Arthrosc 5: 262-7, 1997

11.       Hangody L, Kish G, Karpati Z, et al.: Mosaicplasty for the treatment of articular cartilage defects: application in clinical practice. Orthopedics 21: 751-6, 1998

12.       Homminga GN, Bulstra SK, Bouwmeester PS, et al.: Perichondral grafting for cartilage lesions of the knee. J Bone Joint Surg Br 72: 1003-7, 1990

13.       Messner K, Maletius W: The long-term prognosis for severe damage to weight-bearing cartilage in the knee: a 14-year clinical and radiographic follow-up in 28 young athletes. Acta Orthop Scand 67: 165-8, 1996

14.       Minas T: The role of cartilage repair techniques, including chondrocyte transplantation, in focal chondral knee damage. Instr Course Lect 48, 629-43, 1999

15.       Minas T, Nehrer S: Current concepts in the treatment of articular cartilage defects. Orthopedics 20: 525-38, 1997

16.       Noyes FR, Bassett RW, Grood ES, et al.: Arthroscopy in acute traumatic hemarthrosis of the knee. Incidence of anterior cruciate tears and other injuries. J Bone Joint Surg 62 Am: 687-95, 1980

17.       Peterson L: Current approaches and results of chondrocyte implantation, American Acedemy of Orthopeadic Surgeons 64th Annual Meeting American Acedemy of Orthopeadic Surgeons, Rosemont, IL, San Francisco, CA, pp. 183, 1997.

18.       Pridie KH: Abstract: A method of resurfacing osteoarthritic knee joints. J Bone Joint Surg 41 Br: 618-9, 1959

19.       Steadman JR, Rodkey WG, Briggs KK, et al.: The microfracture technic in the management of complete cartilage defects in the knee joint. Orthopade 28: 26-32, 1999

20.       Steadman JR, Rodkey WG, Singleton SB, et al.: Microfracture technic for full-thickness chondral defects. Technique and clinical results. Op Tech Orthop 7, 300-4, 1997

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