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Editorial Commentary: Autologous Chondrocyte Implantation Versus Microfracture for Knee Articular Cartilage Repair: We Should Focus on the Latest Autologous Chondrocyte Implantation Techniques
Editorial Commentary: Autologous Chondrocyte Implantation Versus Microfracture for Knee Articular Cartilage Repair: We Should Focus on the Latest Autologous Chondrocyte Implantation Techniques John Wilson Belk, B.S., and Eric McCarty, M.D.
Abstract: The clinical efficacy of autologous chondrocyte implantation (ACI) versus microfracture (MFx) for repair of articular cartilage lesions in the knee has gained significant attention in the orthopaedic sports medicine community in recent years. Bone marrow stimulation with MFx often is considered a first-line treatment option, given the ease and low cost of the procedure, as well as the good short-term outcomes. However, multiple studies have recently shown the outcomes of knee MFx to worsen after 5 years postoperatively, particularly for larger lesions. Because of this, ACI has been proposed as a first-line rather than salvage procedure for focal chondral defects in the knee. Although it is important to understand the differences in clinical outcomes between ACI and MFx at mid-term follow-up, longer-term outcomes need to be further investigated. In addition, it may be more appropriate to focus on the comparison of MFx with newergeneration techniques of chondrocyte implantation matrixeassociated ACI rather than a collation of historical 2-step ACI using periosteum and newer techniques.
See related article on page 289
F
ollowing injury, articular cartilage has been limited to no ability to spontaneously repair, largely due to its avascular status.1,2 If left untreated, full-thickness chondral defects can lead to degenerative joint symptoms such as pain, swelling, and joint dysfunction,3 and thus often require surgical intervention. Multiple studies have suggested microfracture (MFx) as a firstline treatment option due to its low cost and ability to introduce blood content into the injury site through bone marrow stimulation.4-7 However, because of the tendency for outcomes following MFx to worsen after 5 years postoperatively,8-11 autologous chondrocyte implantation (ACI) recently has gained traction as a first-
University of Colorado School of Medicine The authors report the following potential conflict of interest or source of funding: E.M. reports other from Zimmer Biomet, grants from Smith & Nephew, grants from Arthrex, and grants from Mitek, outside the submitted work. Full ICMJE author disclosure forms are available for this article online, as supplementary material. Ó 2019 by the Arthroscopy Association of North America 0749-8063/191076/$36.00 https://doi.org/10.1016/j.arthro.2019.09.004
304
line procedure.12 The clinical outcomes following ACI versus MFx have been well reported at the short- to mid-term follow-up, although further investigation of long-term outcomes is needed to determine the clinical efficacy of these treatment options. The study reported in this issue by Guo-Hau, FengJen, Sheng-Hao, Pao-Ju, Jia-Fwu, Ching-Feng, and RuYu13 entitled “Autologous Chondrocyte Implantation Versus Microfracture in the Knee: A Meta-analysis and Systematic Review” provides an in-depth mathematical analysis of randomized controlled trials for determining clinical outcomes of ACI versus MFx for repair of articular cartilage lesions in the knee at mid-term follow-up. The authors should be praised for their work on this topic and for providing reliable data that may be useful for orthopaedic surgeons in the operating room. However, given the shortage of studies that evaluate ACI or MFx at the long-term follow-up, the efficacy of these procedures at 10 to 20 years postoperatively remains unclear. Multiple studies over the last few years have reported clinical outcomes of articular cartilage repair with ACI versus Mfx, with conflicting results. Some studies have
Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 36, No 1 (January), 2020: pp 304-306
EDITORIAL COMMENTARY
shown no difference between groups,14-16 some have suggested MFx as the preferred line of treatment,5,17 and some have shown ACI to be significantly better when compared with MFx.18-21 Although the statistical analysis provided by Guo-Hau et al.13 may prove useful, we must have more data on the long-term outcomes of ACI and MFx before designating a superior line of treatment or even lack thereof for repair of articular cartilage lesions in the knee. It appears that the conflicting results reported in the literature might be at least partially explained by the surgical technique for ACI used in these studies. The studies that show either no difference between groups or a preference for MFx mainly used ACI-P,5,14-16 a 2step procedure in which a cartilage biopsy is collected via knee arthroscopy, and the cultured chondrocytes are then implanted into the injury site and covered by a portion of the patient’s periosteum. Conversely, studies that demonstrate improved outcomes with ACI should be interpreted cautiously due to the heterogeneity in surgical technique. These studies18-22 used matrixassociated autologous chondrocyte implantation (MACI), a NeoCart implant, or ChondroCelect ACI, all of which use different methods for cell-extraction. Of these 3 techniques, only one is currently available for use for surgeons in the United States (MACI). MFx has been demonstrated as the preferred line of treatment over ACI due to the increased technical demand of the ACI procedure. However, there is much debate regarding the sustainability of improved outcomes at the short- to mid-term follow-up with MFx. Additional high-quality studies on repair of articular cartilage lesions in the knee with ACI versus MFx are necessary to better define the 10- to 20-year clinical and functional outcomes between these 2 groups and to delineate the indication of a superior treatment option, if one exists. Furthermore, it may be more appropriate to follow closely the outcomes of newer advanced techniques of chondrocyte implantation (MACI) rather than historical (ACI-P).
References 1. Buckwalter JA. Articular cartilage injuries. Clin Orthop Relat Res 2002;402:21-37. 2. 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;14:1119-1125. 3. Brix MO, Stelzeneder D, Chiari C, et al. Treatment of fullthickness chondral defects with Hyalograft C in the knee: Long-term results. Am J Sports Med 2014;42:1426-1432. 4. Bekkers JE, Inklaar M, Saris DB. Treatment selection in articular cartilage lesions of the knee: A systematic review. Am J Sports Med 2009;37:148S-155S (suppl 1).
305
5. Lim HC, Bae JH, Song SH, Park YE, Kim SJ. Current treatments of isolated articular cartilage lesions of the knee achieve similar outcomes. Clin Orthop Relat Res 2012;470:2261-2267. 6. Mithoefer K, McAdams T, Williams RJ, Kreuz PC, Mandelbaum BR. Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: An evidence-based systematic analysis. Am J Sports Med 2009;37:2053-2063. 7. Williams RJ III, Harnly HW. Microfracture: Indications, technique, and results. Instr Course Lect 2007;56: 419-428. 8. Gobbi A, Karnatzikos G, Kumar A. Long-term results after microfracture treatment for full-thickness knee chondral lesions in athletes. Knee Surg Sports Traumatol Arthrosc 2014;22:1986-1996. 9. Goyal D, Keyhani S, Lee EH, Hui JH. Evidence-based status of microfracture technique: A systematic review of level I and II studies. Arthroscopy 2013;29:1579-1588. 10. Solheim E, Hegna J, Inderhaug E, Øyen J, Harlem T, Strand T. Results at 10-14 years after microfracture treatment of articular cartilage defects in the knee. Knee Surg Sports Traumatol Arthrosc 2016;24:1587-1593. 11. Von Keudell A, Atzwanger J, Forstner R, Resch H, Hoffelner T, Mayer M. Radiological evaluation of cartilage after microfracture treatment: A long-term follow-up study. Eur J Radiol 2012;81:1618-1624. 12. Welch T, Mandelbaum B, Tom M. Autologous chondrocyte implantation: Past, present, and future. Sports Med Arthrosc 2016;24:85-91. 13. Gou-Hau G, Feng-Jen T, Sheng-Hao W, et al. Autologous chondrocyte implantation versus microfracture in the knee: A meta-analysis and systematic review. Arthroscopy 2020;36:289-303. 14. Knutsen G, Drogset JO, Engebretsen L, et al. A randomized multicenter trial comparing autologous chondrocyte implantation with microfracture: Long-term follow-up at 14 to 15 years. J Bone Joint Surg Am 2016;98:1332-1339. 15. Knutsen G, Engebretsen L, Ludvigsen TC, et al.; Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial. J Bone Joint Surg Am 2004;86:455-464. 16. Kraeutler MJ, Belk JW, Purcell JM, McCarty EC. Microfracture versus autologous chondrocyte implantation for articular cartilage lesions in the knee: A systematic review of 5-year outcomes. Am J Sports Med 2018;46:995-999. 17. Van Assche D, Staes F, Van Caspel D, et al. Autologous chondrocyte implantation versus microfracture for knee cartilage injury: A prospective randomized trial, with 2year follow-up. Knee Surg Sports Traumatol Arthrosc 2010;18:486-495. 18. Saris D, Price A, Widuchowski W, et al. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: Two-year follow-up of a prospective randomized trial. Am J Sports Med 2014;42:1384-1394. 19. Crawford DC, DeBerardino TM, Williams RJ 3rd. NeoCart, an autologous cartilage tissue implant, compared
306
EDITORIAL COMMENTARY
with microfracture for treatment of distal femoral cartilage lesions: An FDA phase-II prospective, randomized clinical trial after two years. J Bone Joint Surg Am 2012;94: 979-989. 20. Vanlauwe J, Saris DB, Victor J, et al. Five-year outcome of characterized chondrocyte implantation versus microfracture for symptomatic cartilage defects of the knee: Early treatment matters. Am J Sports Med 2011;39: 2566-2574.
21. Brittberg M, Recker D, Ilgenfritz J, et al. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: Five-year follow-up of a prospective randomized trial. Am J Sports Med 2018;46:1343-1351. 22. Saris DB, Vanlauwe J, Victor J, et al. 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;37:10S-19S (suppl 1).
Abstract: The clinical efficacy of autologous chondrocyte implantation (ACI) versus microfracture (MFx) for repair of articular cartilage lesions in the knee has gained significant attention in the orthopaedic sports medicine community in recent years. Bone marrow stimulation with MFx often is considered a first-line treatment option, given the ease and low cost of the procedure, as well as the good short-term outcomes. However, multiple studies have recently shown the outcomes of knee MFx to worsen after 5 years postoperatively, particularly for larger lesions. Because of this, ACI has been proposed as a first-line rather than salvage procedure for focal chondral defects in the knee. Although it is important to understand the differences in clinical outcomes between ACI and MFx at mid-term follow-up, longer-term outcomes need to be further investigated. In addition, it may be more appropriate to focus on the comparison of MFx with newergeneration techniques of chondrocyte implantation matrixeassociated ACI rather than a collation of historical 2-step ACI using periosteum and newer techniques.
See related article on page 289
F
ollowing injury, articular cartilage has been limited to no ability to spontaneously repair, largely due to its avascular status.1,2 If left untreated, full-thickness chondral defects can lead to degenerative joint symptoms such as pain, swelling, and joint dysfunction,3 and thus often require surgical intervention. Multiple studies have suggested microfracture (MFx) as a firstline treatment option due to its low cost and ability to introduce blood content into the injury site through bone marrow stimulation.4-7 However, because of the tendency for outcomes following MFx to worsen after 5 years postoperatively,8-11 autologous chondrocyte implantation (ACI) recently has gained traction as a first-
University of Colorado School of Medicine The authors report the following potential conflict of interest or source of funding: E.M. reports other from Zimmer Biomet, grants from Smith & Nephew, grants from Arthrex, and grants from Mitek, outside the submitted work. Full ICMJE author disclosure forms are available for this article online, as supplementary material. Ó 2019 by the Arthroscopy Association of North America 0749-8063/191076/$36.00 https://doi.org/10.1016/j.arthro.2019.09.004
304
line procedure.12 The clinical outcomes following ACI versus MFx have been well reported at the short- to mid-term follow-up, although further investigation of long-term outcomes is needed to determine the clinical efficacy of these treatment options. The study reported in this issue by Guo-Hau, FengJen, Sheng-Hao, Pao-Ju, Jia-Fwu, Ching-Feng, and RuYu13 entitled “Autologous Chondrocyte Implantation Versus Microfracture in the Knee: A Meta-analysis and Systematic Review” provides an in-depth mathematical analysis of randomized controlled trials for determining clinical outcomes of ACI versus MFx for repair of articular cartilage lesions in the knee at mid-term follow-up. The authors should be praised for their work on this topic and for providing reliable data that may be useful for orthopaedic surgeons in the operating room. However, given the shortage of studies that evaluate ACI or MFx at the long-term follow-up, the efficacy of these procedures at 10 to 20 years postoperatively remains unclear. Multiple studies over the last few years have reported clinical outcomes of articular cartilage repair with ACI versus Mfx, with conflicting results. Some studies have
Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 36, No 1 (January), 2020: pp 304-306
EDITORIAL COMMENTARY
shown no difference between groups,14-16 some have suggested MFx as the preferred line of treatment,5,17 and some have shown ACI to be significantly better when compared with MFx.18-21 Although the statistical analysis provided by Guo-Hau et al.13 may prove useful, we must have more data on the long-term outcomes of ACI and MFx before designating a superior line of treatment or even lack thereof for repair of articular cartilage lesions in the knee. It appears that the conflicting results reported in the literature might be at least partially explained by the surgical technique for ACI used in these studies. The studies that show either no difference between groups or a preference for MFx mainly used ACI-P,5,14-16 a 2step procedure in which a cartilage biopsy is collected via knee arthroscopy, and the cultured chondrocytes are then implanted into the injury site and covered by a portion of the patient’s periosteum. Conversely, studies that demonstrate improved outcomes with ACI should be interpreted cautiously due to the heterogeneity in surgical technique. These studies18-22 used matrixassociated autologous chondrocyte implantation (MACI), a NeoCart implant, or ChondroCelect ACI, all of which use different methods for cell-extraction. Of these 3 techniques, only one is currently available for use for surgeons in the United States (MACI). MFx has been demonstrated as the preferred line of treatment over ACI due to the increased technical demand of the ACI procedure. However, there is much debate regarding the sustainability of improved outcomes at the short- to mid-term follow-up with MFx. Additional high-quality studies on repair of articular cartilage lesions in the knee with ACI versus MFx are necessary to better define the 10- to 20-year clinical and functional outcomes between these 2 groups and to delineate the indication of a superior treatment option, if one exists. Furthermore, it may be more appropriate to follow closely the outcomes of newer advanced techniques of chondrocyte implantation (MACI) rather than historical (ACI-P).
References 1. Buckwalter JA. Articular cartilage injuries. Clin Orthop Relat Res 2002;402:21-37. 2. 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;14:1119-1125. 3. Brix MO, Stelzeneder D, Chiari C, et al. Treatment of fullthickness chondral defects with Hyalograft C in the knee: Long-term results. Am J Sports Med 2014;42:1426-1432. 4. Bekkers JE, Inklaar M, Saris DB. Treatment selection in articular cartilage lesions of the knee: A systematic review. Am J Sports Med 2009;37:148S-155S (suppl 1).
305
5. Lim HC, Bae JH, Song SH, Park YE, Kim SJ. Current treatments of isolated articular cartilage lesions of the knee achieve similar outcomes. Clin Orthop Relat Res 2012;470:2261-2267. 6. Mithoefer K, McAdams T, Williams RJ, Kreuz PC, Mandelbaum BR. Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: An evidence-based systematic analysis. Am J Sports Med 2009;37:2053-2063. 7. Williams RJ III, Harnly HW. Microfracture: Indications, technique, and results. Instr Course Lect 2007;56: 419-428. 8. Gobbi A, Karnatzikos G, Kumar A. Long-term results after microfracture treatment for full-thickness knee chondral lesions in athletes. Knee Surg Sports Traumatol Arthrosc 2014;22:1986-1996. 9. Goyal D, Keyhani S, Lee EH, Hui JH. Evidence-based status of microfracture technique: A systematic review of level I and II studies. Arthroscopy 2013;29:1579-1588. 10. Solheim E, Hegna J, Inderhaug E, Øyen J, Harlem T, Strand T. Results at 10-14 years after microfracture treatment of articular cartilage defects in the knee. Knee Surg Sports Traumatol Arthrosc 2016;24:1587-1593. 11. Von Keudell A, Atzwanger J, Forstner R, Resch H, Hoffelner T, Mayer M. Radiological evaluation of cartilage after microfracture treatment: A long-term follow-up study. Eur J Radiol 2012;81:1618-1624. 12. Welch T, Mandelbaum B, Tom M. Autologous chondrocyte implantation: Past, present, and future. Sports Med Arthrosc 2016;24:85-91. 13. Gou-Hau G, Feng-Jen T, Sheng-Hao W, et al. Autologous chondrocyte implantation versus microfracture in the knee: A meta-analysis and systematic review. Arthroscopy 2020;36:289-303. 14. Knutsen G, Drogset JO, Engebretsen L, et al. A randomized multicenter trial comparing autologous chondrocyte implantation with microfracture: Long-term follow-up at 14 to 15 years. J Bone Joint Surg Am 2016;98:1332-1339. 15. Knutsen G, Engebretsen L, Ludvigsen TC, et al.; Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial. J Bone Joint Surg Am 2004;86:455-464. 16. Kraeutler MJ, Belk JW, Purcell JM, McCarty EC. Microfracture versus autologous chondrocyte implantation for articular cartilage lesions in the knee: A systematic review of 5-year outcomes. Am J Sports Med 2018;46:995-999. 17. Van Assche D, Staes F, Van Caspel D, et al. Autologous chondrocyte implantation versus microfracture for knee cartilage injury: A prospective randomized trial, with 2year follow-up. Knee Surg Sports Traumatol Arthrosc 2010;18:486-495. 18. Saris D, Price A, Widuchowski W, et al. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: Two-year follow-up of a prospective randomized trial. Am J Sports Med 2014;42:1384-1394. 19. Crawford DC, DeBerardino TM, Williams RJ 3rd. NeoCart, an autologous cartilage tissue implant, compared
306
EDITORIAL COMMENTARY
with microfracture for treatment of distal femoral cartilage lesions: An FDA phase-II prospective, randomized clinical trial after two years. J Bone Joint Surg Am 2012;94: 979-989. 20. Vanlauwe J, Saris DB, Victor J, et al. Five-year outcome of characterized chondrocyte implantation versus microfracture for symptomatic cartilage defects of the knee: Early treatment matters. Am J Sports Med 2011;39: 2566-2574.
21. Brittberg M, Recker D, Ilgenfritz J, et al. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: Five-year follow-up of a prospective randomized trial. Am J Sports Med 2018;46:1343-1351. 22. Saris DB, Vanlauwe J, Victor J, et al. 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;37:10S-19S (suppl 1).