J Knee Surg 2013; 26(03): 203-212
DOI: 10.1055/s-0032-1329231
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Factors Influencing the Outcome of Autologous Chondrocyte Implantation: A Systematic Review

Omar A. Behery
1   Division of Sports Medicine and Cartilage Restoration Program, Department of Orthopaedics, The Ohio State University, Columbus, Ohio
,
Joshua D. Harris
1   Division of Sports Medicine and Cartilage Restoration Program, Department of Orthopaedics, The Ohio State University, Columbus, Ohio
,
Jonathan M. Karnes
1   Division of Sports Medicine and Cartilage Restoration Program, Department of Orthopaedics, The Ohio State University, Columbus, Ohio
,
Robert A. Siston
2   Department of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, Ohio
,
David C. Flanigan
1   Division of Sports Medicine and Cartilage Restoration Program, Department of Orthopaedics, The Ohio State University, Columbus, Ohio
› Author Affiliations
Further Information

Publication History

26 April 2012

23 August 2012

Publication Date:
12 November 2012 (online)

Abstract

Autologous chondrocyte implantation (ACI) is an effective method of treatment of chondral defects of the knee. ACI outcomes are influenced by patient-, knee-, and lesion-specific factors. We compiled subject-level data from current studies on ACI and quantitatively analyzed this data set for associations between patient-, knee-, and lesion-specific factors and the outcome of ACI surgery. A systematic review of studies investigating ACI treatment outcomes in the knee was performed. Only studies that published subject-level data were included. Data on patient and lesion characteristics, as well as clinical outcome scores, were collected. Thirteen studies (305 defects) were included in this review. These studies showed that ACI treatment improves clinical outcomes in different patient populations. However, subject-specific variables such as patient age, gender, body mass index, duration of preoperative symptoms, as well as defect size and location were not associated with International Knee Documentation Committee score or visual analog scale score changes (p > 0.05 for all). Covariate analysis showed that patient age was related to symptom duration prior to surgery (p = 0.009). ACI surgery has been shown to improve outcomes in patients with chondral lesions of the knee. Despite evidence in the literature showing that multiple patient-, knee-, and lesion-specific factors may influence treatment outcomes, our review shows that these factors, solely, do not affect outcomes. However, together, they may synergistically affect outcomes.

 
  • References

  • 1 Arøen A, Løken S, Heir S , et al. Articular cartilage lesions in 993 consecutive knee arthroscopies. Am J Sports Med 2004; 32 (1) 211-215
  • 2 Curl WW, Krome J, Gordon ES, Rushing J, Smith BP, Poehling GG. Cartilage injuries: a review of 31,516 knee arthroscopies. Arthroscopy 1997; 13 (4) 456-460
  • 3 Hjelle K, Solheim E, Strand T, Muri R, Brittberg M. Articular cartilage defects in 1,000 knee arthroscopies. Arthroscopy 2002; 18 (7) 730-734
  • 4 Widuchowski W, Widuchowski J, Koczy B, Szyluk K. Untreated asymptomatic deep cartilage lesions associated with anterior cruciate ligament injury: results at 10- and 15-year follow-up. Am J Sports Med 2009; 37 (4) 688-692
  • 5 Flanigan DC, Harris JD, Trinh TQ, Siston RA, Brophy RH. Prevalence of chondral defects in athletes' knees: a systematic review. Med Sci Sports Exerc 2010; 42 (10) 1795-1801
  • 6 Wang Y, Ding C, Wluka AE , et al. Factors affecting progression of knee cartilage defects in normal subjects over 2 years. Rheumatology (Oxford) 2006; 45 (1) 79-84
  • 7 Alford JW, Cole BJ. Cartilage restoration, part 1: basic science, historical perspective, patient evaluation, and treatment options. Am J Sports Med 2005; 33 (2) 295-306
  • 8 Alford JW, Cole BJ. Cartilage restoration, part 2: techniques, outcomes, and future directions. Am J Sports Med 2005; 33 (3) 443-460
  • 9 Harris JD, Siston RA, Brophy RH, Lattermann C, Carey JL, Flanigan DC. Failures, re-operations, and complications after autologous chondrocyte implantation—a systematic review. Osteoarthritis Cartilage 2011; 19 (7) 779-791
  • 10 Henderson IJ, Tuy B, Connell D, Oakes B, Hettwer WH. Prospective clinical study of autologous chondrocyte implantation and correlation with MRI at three and 12 months. J Bone Joint Surg Br 2003; 85 (7) 1060-1066
  • 11 Wondrasch B, Zak L, Welsch GH, Marlovits S. Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle on radiographic and clinical outcome after 2 years: a prospective, randomized controlled pilot study. Am J Sports Med 2009; 37 (Suppl. 01) 88S-96S
  • 12 Vasiliadis HS, Danielson B, Ljungberg M, McKeon B, Lindahl A, Peterson L. Autologous chondrocyte implantation in cartilage lesions of the knee: long-term evaluation with magnetic resonance imaging and delayed gadolinium-enhanced magnetic resonance imaging technique. Am J Sports Med 2010; 38 (5) 943-949
  • 13 Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 1994; 331 (14) 889-895
  • 14 Bodian CA, Freedman G, Hossain S, Eisenkraft JB, Beilin Y. The visual analog scale for pain: clinical significance in postoperative patients. Anesthesiology 2001; 95 (6) 1356-1361
  • 15 Bekkers JE, de Windt TS, Raijmakers NJ, Dhert WJ, Saris DB. Validation of the Knee Injury and Osteoarthritis Outcome Score (KOOS) for the treatment of focal cartilage lesions. Osteoarthritis Cartilage 2009; 17 (11) 1434-1439
  • 16 Schmitt LC, Paterno MV, Huang S. Validity and internal consistency of the international knee documentation committee subjective knee evaluation form in children and adolescents. Am J Sports Med 2010; 38 (12) 2443-2447
  • 17 Crawford DC, Heveran CM, Cannon Jr WD, Foo LF, Potter HG. An autologous cartilage tissue implant NeoCart for treatment of grade III chondral injury to the distal femur: prospective clinical safety trial at 2 years. Am J Sports Med 2009; 37 (7) 1334-1343
  • 18 Gobbi A, Kon E, Berruto M , et al. Patellofemoral full-thickness chondral defects treated with second-generation autologous chondrocyte implantation: results at 5 years' follow-up. Am J Sports Med 2009; 37 (6) 1083-1092
  • 19 Steinhagen J, Bruns J, Deuretzbacher G, Ruether W, Fuerst M, Niggemeyer O. Treatment of osteochondritis dissecans of the femoral condyle with autologous bone grafts and matrix-supported autologous chondrocytes. Int Orthop 2010; 34 (6) 819-825
  • 20 Franceschi F, Longo UG, Ruzzini L, Marinozzi A, Maffulli N, Denaro V. Simultaneous arthroscopic implantation of autologous chondrocytes and high tibial osteotomy for tibial chondral defects in the varus knee. Knee 2008; 15 (4) 309-313
  • 21 Bhosale AM, Myint P, Roberts S , et al. Combined autologous chondrocyte implantation and allogenic meniscus transplantation: a biological knee replacement. Knee 2007; 14 (5) 361-368
  • 22 Amin AA, Bartlett W, Gooding CR , et al. The use of autologous chondrocyte implantation following and combined with anterior cruciate ligament reconstruction. Int Orthop 2006; 30 (1) 48-53
  • 23 Behrens P, Bitter T, Kurz B, Russlies M. Matrix-associated autologous chondrocyte transplantation/implantation (MACT/MACI)—5-year follow-up. Knee 2006; 13 (3) 194-202
  • 24 Halbrecht JL, Klick BC. Improvement in bone homeostasis following autologous chondrocyte implantation of the knee. Orthopedics 2006; 29 (1) 61-69
  • 25 Marcacci M, Berruto M, Brocchetta D , et al. Articular cartilage engineering with Hyalograft C: 3-year clinical results. Clin Orthop Relat Res 2005; 435 (435) 96-105
  • 26 Mithöfer K, Minas T, Peterson L, Yeon H, Micheli LJ. Functional outcome of knee articular cartilage repair in adolescent athletes. Am J Sports Med 2005; 33 (8) 1147-1153
  • 27 Vasara AI, Nieminen MT, Jurvelin JS, Peterson L, Lindahl A, Kiviranta I. Indentation stiffness of repair tissue after autologous chondrocyte transplantation. Clin Orthop Relat Res 2005; 433 (433) 233-242
  • 28 Henderson I, Tuy B, Oakes B. Reoperation after autologous chondrocyte implantation. Indications and findings. J Bone Joint Surg Br 2004; 86 (2) 205-211
  • 29 Peterson L, Minas T, Brittberg M, Nilsson A, Sjögren-Jansson E, Lindahl A. Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. Clin Orthop Relat Res 2000; 374 (374) 212-234
  • 30 Flanigan DC, Harris JD, Brockmeier PM, Siston RA. The effects of lesion size and location on subchondral bone contact in experimental knee articular cartilage defects in a bovine model. Arthroscopy 2010; 26 (12) 1655-1661
  • 31 Minas T, Nehrer S. Current concepts in the treatment of articular cartilage defects. Orthopedics 1997; 20 (6) 525-538
  • 32 Saris D, Dhert W, Verbout A. Joint homeostasis: The discrepancy between old and fresh defects in cartilage repair. J Bone Joint Surg Br 2003; 85 (7) 1067-1076
  • 33 Saris DB, Vanlauwe J, Victor J , et al; TIG/ACT/01/2000&EXT Study Group. Treatment of symptomatic cartilage defects of the knee: characterized chondrocyte implantation results in better clinical outcome at 36 months in a randomized trial compared to microfracture. Am J Sports Med 2009; 37 (Suppl. 01) 10S-19S
  • 34 Bhosale AM, Kuiper JH, Johnson WE, Harrison PE, Richardson JB. Midterm to long-term longitudinal outcome of autologous chondrocyte implantation in the knee joint: a multilevel analysis. Am J Sports Med 2009; 37 (Suppl. 01) 131S-138S
  • 35 Niemeyer P, Köstler W, Salzmann GM, Lenz P, Kreuz PC, Südkamp NP. Autologous chondrocyte implantation for treatment of focal cartilage defects in patients age 40 years and older: A matched-pair analysis with 2-year follow-up. Am J Sports Med 2010; 38 (12) 2410-2416
  • 36 Rosenberger RE, Gomoll AH, Bryant T, Minas T. Repair of large chondral defects of the knee with autologous chondrocyte implantation in patients 45 years or older. Am J Sports Med 2008; 36 (12) 2336-2344
  • 37 Minas T, Gomoll AH, Solhpour S, Rosenberger R, Probst C, Bryant T. Autologous chondrocyte implantation for joint preservation in patients with early osteoarthritis. Clin Orthop Relat Res 2010; 468 (1) 147-157
  • 38 Knutsen G, Engebretsen L, Ludvigsen T , et al. Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial. J Bone Joint Surg Am 2004; 86A (3) 455-464
  • 39 Micheli LJ, Browne JE, Erggelet C , et al. Autologous chondrocyte implantation of the knee: multicenter experience and minimum 3-year follow-up. Clin J Sport Med 2001; 11 (4) 223-228
  • 40 Mithoefer K, Hambly K, Della Villa S, Silvers H, Mandelbaum BR. Return to sports participation after articular cartilage repair in the knee: scientific evidence. Am J Sports Med 2009; 37 (Suppl. 01) 167S-176S
  • 41 Asik M, Ciftci F, Sen C, Erdil M, Atalar A. The microfracture technique for the treatment of full-thickness articular cartilage lesions of the knee: midterm results. Arthroscopy 2008; 24 (11) 1214-1220
  • 42 Gudas R, Kalesinkas R, Kimtys V , et al. A prospective randomized clinical study of mosaic osteochondral autologous transplantation versus microfracture for the treatment of osteochondral defects in the knee joint in young athletes. Arthroscopy 2005; 21 (9) 1066-1075
  • 43 Mithoefer K, Williams III RJ, Warren RF, Wickiewicz TL, Marx RG. High-impact athletics after knee articular cartilage repair: a prospective evaluation of the microfracture technique. Am J Sports Med 2006; 34 (9) 1413-1418
  • 44 Jakob RP, Franz T, Gautier E, Mainil-Varlet P. Autologous osteochondral grafting in the knee: indication, results, and reflections. Clin Orthop Relat Res 2002; (401) 170-184
  • 45 Jungmann PM, Salzmann GM, Schmal H, Pestka JM, Südkamp NP, Niemeyer P. Autologous chondrocyte implantation for treatment of cartilage defects of the knee: what predicts the need for reintervention?. Am J Sports Med 2012; 40 (1) 58-67
  • 46 Kreuz PC, Steinwachs MR, Erggelet C , et al. Results after microfracture of full-thickness chondral defects in different compartments in the knee. Osteoarthritis Cartilage 2006; 14 (11) 1119-1125
  • 47 Harris JD, Solak KK, Siston RA, Litsky A, Richards J, Flanigan DC. Contact pressure comparison of proud osteochondral autograft plugs versus proud synthetic plugs. Orthopedics 2011; 34 (2) 97
  • 48 Mithoefer K, Williams R, Warren R , et al. The microfracture technique for the treatment of articular cartilage lesions in the knee. A prospective cohort study. J Bone Joint Surg Am 2005; 87 (9) 1911-1920
  • 49 Gille J, Schuseil E, Wimmer J, Gellissen J, Schulz AP, Behrens P. Mid-term results of Autologous Matrix-Induced Chondrogenesis for treatment of focal cartilage defects in the knee. Knee Surg Sports Traumatol Arthrosc 2010; 18 (11) 1456-1464
  • 50 Gillogly SD, Myers TH, Reinold MM. Treatment of full-thickness chondral defects in the knee with autologous chondrocyte implantation. J Orthop Sports Phys Ther 2006; 36 (10) 751-764
  • 51 Harris JD, Siston RA, Pan X, Flanigan DC. Autologous chondrocyte implantation: a systematic review. J Bone Joint Surg Am 2010; 92 (12) 2220-2233
  • 52 Niemeyer P, Salzmann GM, Hirschmüller A, Südkamp NP. [Factors that influence clinical outcome following autologous chondrocyte implantation for cartilage defects of the knee]. Z Orthop Unfall 2012; 150 (1) 83-88
  • 53 McNickle AG, L'Heureux DR, Yanke AB, Cole BJ. Outcomes of autologous chondrocyte implantation in a diverse patient population. Am J Sports Med 2009; 37 (7) 1344-1350