Stellenwert der matrixaugmentierten Knochenmarkstimulation in der Behandlung von Knorpelschäden des Kniegelenks: Konsensusempfehlungen der AG Klinische Geweberegeneration der DGOU

Zusammenfassung

Für die operative Sanierung lokalisiert vollschichtiger Knorpelschäden der großen Gelenke stehen mit den Transplantationstechniken (autologe Knorpelzelltransplantation, autologe osteochondrale Transplantation) und knochenmarkstimulierenden Techniken unterschiedliche Therapieoptionen zur Verfügung. Vor allem für das Kniegelenk konnte aufgrund der verbesserten Studienlage das jeweils geeignete Anwendungsspektrum dieser Verfahren in letzter Zeit weiter präzisiert werden. Für die matrixaugmentierte Mikrofrakturierung als einzeitige Methode besteht jedoch noch keine genauere Indikationsabgrenzung, insbesondere auch nicht gegenüber den bereits etablierten Verfahren. In der vorliegenden Arbeit werden die derzeit für diese Methode zur Verfügung stehenden Biomaterialien und Anwendungsvarianten beschrieben und ihre präklinische und klinische Evidenz zusammengefasst. Grundsätzlich kann dabei festgestellt werden, dass sich die verschiedenen in diesem Bereich angebotenen Produkte hinsichtlich der Zahl und Qualität zugehöriger Studien (Evidenzlevel) noch erheblich voneinander unterscheiden. Um die matrixaugmentierte Mikrofrakturierung im Sinne einer ersten Indikationsempfehlung als Methode in den therapeutischen Algorithmus der knorpelrekonstruktiven Verfahren im Knie einzuordnen, wurde durch die Mitglieder der Arbeitsgemeinschaft (AG) Klinische Geweberegeneration der Deutschen Gesellschaft für Orthopädie und Unfallchirurgie (DGOU) im Rahmen eines Konsensusprozesses eine Bewertung der verfügbaren Evidenz vorgenommen. Vor dem Hintergrund der aktuellen Datenlage wird ihre Anwendung derzeit im Grenzbereich zwischen Zelltransplantations- und knochenmarkstimulierenden Techniken sowie als Verbesserung der klassischen Mikrofrakturierung und überwiegend im Indikationsbereich der Mikrofrakturierung gesehen. Die Empfehlungen der AG haben vorläufigen und orientierenden Charakter und bedürfen einer erneuten Überprüfung nach Verbesserung der Studienlage.

Abstract

Surgical principles for treatment of full-thickness cartilage defects of the knee include bone marrow stimulation techniques (i.e. arthroscopic microfracturing) and transplantation techniques (i.e. autologous chondrocyte implantation and osteochondral transplantation). On the basis of increasing scientific evidence, indications for these established therapeutical concepts have been specified and clear recommendations for practical use have been given. Within recent years, matrix-augmented bone marrow stimulation has been established as a new treatment concept for chondral lesions. To date, scientific evidence is limited and specific indications are still unclear. The present paper gives an overview of available products as well as preclinical and clinical scientific evidence. On the basis of the present evidence and an expert consensus from the “Working Group on Tissue Regeneration” of the German Orthopaedic and Trauma Society (DGOU), indications are specified and recommendations for the use of matrix-augmented bone marrow stimulation are given. In principle, it can be stated that the various products offered in this field differ considerably in terms of the number and quality of related studies (evidence level). Against the background of the current data situation, their application is currently seen in the border area between cell transplantation and bone marrow stimulation techniques, but also as an improvement on traditional bone marrow stimulation within the indication range of microfracturing. The recommendations of the Working Group have preliminary character and require re-evaluation after improvement of the study situation.

Schlüsselwörter

Knorpel - Kniegelenk - Knochenmarkstimulation - Mikrofrakturierung - Biomaterial

Key words

cartilage - cartilage defect - microfracture - knee - biomaterial

• Literatur

• 1 Hjelle K, Solheim E, Strand T. et al. Articular cartilage defects in 1,000 knee arthroscopies. Arthroscopy 2002; 18: 730-734 doi:10.1053/jars.2002.32839
• 2 Menetrey J, Unno-Veith F, Madry H. et al. Epidemiology and imaging of the subchondral bone in articular cartilage repair. Knee Surg Sports Traumatol Arthrosc 2010; 18: 463-471 doi:10.1007/s00167-010-1053-0
• 3 Widuchowski W, Lukasik P, Kwiatkowski G. et al. Isolated full thickness chondral injuries. Prevalance and outcome of treatment. A retrospective study of 5233 knee arthroscopies. Acta Chir Orthop Traumatol Cech 2008; 75: 382-386
• 4 Spahn G, Fritz J, Albrecht D. et al. Characteristics and associated factors of Klee cartilage lesions: preliminary baseline-data of more than 1000 patients from the German cartilage registry (KnorpelRegister DGOU). Arch Orthop Trauma Surg 2016; 136: 805-810 doi:10.1007/s00402-016-2432-x
• 5 Niemeyer P, Feucht MJ, Fritz J. et al. Cartilage repair surgery for full-thickness defects of the knee in Germany: indications and epidemiological data from the German Cartilage Registry (KnorpelRegister DGOU). Arch Orthop Trauma Surg 2016; 136: 891-897 doi:10.1007/s00402-016-2453-5
• 6 Niemeyer P, Andereya S, Angele P. et al. Stellenwert der autologen Chondrozytentransplantation (ACT) in der Behandlung von Knorpelschäden des Kniegelenks – Empfehlungen der AG Klinische Geweberegeneration der DGOU. Z Orthop Unfall 2013; 151: 38-47 doi:10.1055/s-0032-1328207
• 7 Brittberg M, Gomoll A, Canseco J. et al. Cartilage repair in the degenerative ageing knee: a narrative review and analysis. Acta Orthop 2016; 87: 26-38
• 8 Behrens P, Bosch U, Bruns J. et al. Indikations- und Durchführungsempfehlungen der Arbeitsgemeinschaft „Geweberegeneration und Gewebeersatz“ zur autologen Chondrozyten-Transplantation (ACT). Z Orthop Ihre Grenzgeb 2004; 142: 529-539 doi:10.1055/s-2004-832353
• 9 Niemeyer P, Albrecht D, Andereya S. et al. Autologous chondrocyte implantation (ACI) for cartilage defects of the knee: a guideline by the working group „Clinical Tissue Regeneration“ of the German Society of Orthopaedics and Trauma (DGOU). Knee 2016; 23: 426-435 doi:10.1016/j.knee.2016.02.001
• 10 Steadman J, Rodkey W, Briggs K. Microfracture to treat full-thicknes chondral defects: surgical technique, rehabilitation, and outcomes. J Knee Surg 2002; 15: 170-176
• 11 Steadman JR, Rodkey WG, Rodrigo JJ. Microfracture: surgical technique and rehabilitation to treat chondral defects. Clin Orthop Relat Res 2001; (391 Suppl.): S362-S369 doi:10.1097/00003086-200110001-00033
• 12 Hancock K, Westermann R, Shamrock A. et al. Trends in knee articular cartilage treatments: an American Board of Orthopaedic Surgery Database Study. J Knee Surg 2018;
• 13 Jaiswal PK, Wong K, Khan WS. Current cell-based strategies for knee cartilage injuries. J Stem Cells 2010; 5: 177-185 doi:jsc.2010.5.4.177
• 14 Khan WS, Johnson DS, Hardingham TE. The potential of stem cells in the treatment of knee cartilage defects. Knee 2010; 17: 369-374 doi:10.1016/j.knee.2009.12.003
• 15 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 doi:10.1007/s00167-013-2676-8
• 16 Steadman J, Briggs K, Matheny L. et al. Outcomes following microfracture of full-thickness articular cartilage lesions of the knee in adolescent patients. J Knee Surg 2014; 28: 145-150 doi:10.1055/s-0034-1373737
• 17 Saris DBF, Vanlauwe J, Victor J. et al. Treatment of symptomatic cartilage defects of the knee: characterized chondrocyte implantation (CCI) 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 doi:10.1177/0363546509350694
• 18 Fortier LA, Cole BJ, McIlwraith CW. Science and animal models of marrow stimulation for cartilage repair. J Knee Surg 2012; 25: 3-8 doi:10.1055/s-0032-1310389
• 19 Mithoefer K, Venugopal V, Manaqibwala M. Incidence, degree, and clinical effect of subchondral bone overgrowth after microfracture in the knee. Am J Sports Med 2016; 44: 2057-2063 doi:10.1177/0363546516645514
• 20 Mithoefer K, McAdams T, Williams RJ. et al. 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 doi:10.1177/0363546508328414
• 21 Benthien JP, Behrens P. Autologous matrix-induced chondrogenesis (AMIC): combining microfracturing and a collagen I/III matrix for articular cartilage resurfacing. Cartilage 2010; 1: 65-68 doi:10.1177/1947603509360044
• 22 Erggelet C, Endres M, Neumann K. et al. Formation of cartilage repair tissue in articular cartilage defects pretreated with microfracture and covered with cell free polymer based implants. J Orthop Res 2009; 27: 1353-1360
• 23 Kramer J, Böhrnsen F, Lindner U. et al. In vivo matrix-guided human mesenchymal stem cells. Cell Mol Life Sci 2006; 63: 616-626
• 24 Zhang C, Cai YZ, Lin XJ. One-step cartilage repair technique as a next generation of cell therapy for cartilage defects: biological characteristics, preclinical application, surgical techniques, and clinical developments. Arthroscopy 2016; 32: 1444-1450 doi:10.1016/j.arthro.2016.01.061
• 25 Frisbie DD, Morisset S, Ho CP. et al. Effects of calcified cartilage on healing of chondral defects treated with microfracture in horses. Am J Sports Med 2006; 34: 1824-1831 doi:10.1177/0363546506289882
• 26 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 doi:10.1016/j.joca.2006.05.003
• 27 Benthien JP, Behrens P. Reviewing subchondral cartilage surgery: considerations for standardised and outcome predictable cartilage remodelling: a technical note. Int Orthop 2013; 37: 2139-2145 doi:10.1007/s00264-013-2025-z
• 28 Shive MS, Stanish WD, McCormack R. et al. BST-CarGel^® treatment maintains cartilage repair superiority over microfracture at 5 years in a multicenter randomized controlled trial. Cartilage 2015; 6: 62-72 doi:10.1177/1947603514562064
• 29 Roessler PP, Pfister B, Gesslein M. et al. Short-term follow up after implantation of a cell-free collagen type I matrix for the treatment of large cartilage defects of the knee. Int Orthop 2015; 39: 2473-2479
• 30 Schüttler KF, Schenker H, Theisen C. et al. Use of cell-free collagen type I matrix implants for the treatment of small cartilage defects in the knee: clinical and magnetic resonance imaging evaluation. Knee Surg Sports Traumatol Arthrosc 2014; 22: 1270-1276
• 31 DʼAntimo C, Biggi F, Borean A. et al. Combining a novel leucocyte-platelet-concentrated membrane and an injectable collagen scaffold in a single-step AMIC procedure to treat chondral lesions of the knee: a preliminary retrospective study. Eur J Orthop Surg Traumatol 2017; 27: 673-681 doi:10.1007/s00590-016-1869-5
• 32 Kim MS, Koh IJ, Choi YJ. et al. Collagen augmentation improves the quality of cartilage repair after microfracture in patients undergoing high tibial osteotomy: a randomized controlled trial. Am J Sports Med 2017; 45: 1845-1855 doi:10.1177/0363546517691942
• 33 Shetty AA, Kim SJ, Bilagi P. et al. Autologous collagen-induced chondrogenesis: single-stage arthroscopic cartilage repair technique. Orthopedics 2013; 36: e648-e652 doi:10.3928/01477447-20130426-30
• 34 Stelzeneder D, Shetty AA, Kim SJ. et al. Repair tissue quality after arthroscopic autologous collagen-induced chondrogenesis (ACIC) assessed via T2* mapping. Skeletal Radiol 2013; 42: 1657-1664 doi:10.1007/s00256-013-1708-2
• 35 Benthien JP, Behrens P. Nanofractured autologous matrix induced chondrogenesis (NAMIC©)–Further development of collagen membrane aided chondrogenesis combined with subchondral needling: a technical note. Knee 2015; 22: 411-415
• 36 Breil-Wirth A, von Engelhardt L, Lobner S. et al. Retrospektive Untersuchung einer zellfreien Matrix zur Knorpeltherapie. OUP 2016; 9: 515-520
• 37 Schneider U. Controlled, randomized multicenter study to compare compatibility and safety of ChondroFiller liquid (cell free 2-component collagen gel) with microfracturing of patients with focal cartilage defects of the knee joint. Video J Orthop Surg 2016; 1: 1-8 doi:10.5348/VNP05-2016-1-OA-1
• 38 Dhollander AA, De Neve F, Almqvist KF. et al. Autologous matrix-induced chondrogenesis combined with platelet-rich plasma gel: technical description and a five pilot patients report. Knee Surg Sports Traumatol Arthrosc 2011; 19: 536-542 doi:10.1007/s00167-010-1337-4
• 39 Dhollander AA, Moens K, Van der Maas J. et al. Treatment of patellofemoral cartilage defects in the knee by autologous matrix-induced chondrogenesis (AMIC). Acta Orthop Belg 2014; 80: 251-259
• 40 Gille J, Schuseil E, Wimmer J. et al. Mid-term results of Autologous Matrix-Induced Chondrogenesis for treatment of focal cartilage defects in the knee. Knee Surg Sports Traumatol Arthrosc 2010; 18: 1456-1464 doi:10.1007/s00167-010-1042-3
• 41 Gille J, Behrens P, Volpi P. et al. Outcome of Autologous Matrix Induced Chondrogenesis (AMIC) in cartilage knee surgery: data of the AMIC Registry. Arch Orthop Trauma Surg 2013; 133: 87-93 doi:10.1007/s00402-012-1621-5
• 42 Gobbi A, Karnatzikos G, Sankineani SR. One-step surgery with multipotent stem cells for the treatment of large full-thickness chondral defects of the knee. Am J Sports Med 2014; 42: 648-657 doi:10.1177/0363546513518007
• 43 Kusano T, Jakob RP, Gautier E. et al. Treatment of isolated chondral and osteochondral defects in the knee by autologous matrix-induced chondrogenesis (AMIC). Knee Surg Sports Traumatol Arthrosc 2012; 20: 2109-2115
• 44 Pascarella A, Ciatti R, Pascarella F. et al. Treatment of articular cartilage lesions of the knee joint using a modified AMIC technique. Knee Surg Sports Traumatol Arthrosc 2010; 18: 509-513 doi:10.1007/s00167-009-1007-6
• 45 Sadlik B, Puszkarz M, Kosmalska L. et al. All-arthroscopic autologous matrix-induced chondrogenesis-aided repair of a patellar cartilage defect using dry arthroscopy and a retraction system. J Knee Surg 2017; 30: 925-929 doi:10.1055/s-0037-1599246
• 46 Schiavone Panni A, Del Regno C, Mazzitelli G. et al. Good clinical results with autologous matrix-induced chondrogenesis (AMIC) technique in large knee chondral defects. Knee Surg Sports Traumatol Arthrosc 2018; 26: 1130-1136 doi:10.1007/s00167-017-4503-0
• 47 Skowroński J, Skowroński R, Rutka M. Large cartilage lesions of the knee treated with bone marrow concentrate and collagen membrane–results. Ortop Traumatol Rehabil 2013; 15: 69-76 doi:10.5604/15093492.1012405
• 48 Volz M, Schaumburger J, Frick H. et al. A randomized controlled trial demonstrating sustained benefit of Autologous Matrix-Induced Chondrogenesis over microfracture at five years. Int Orthop 2017; 41: 797-804 doi:10.1007/s00264-016-3391-0
• 49 Becher C, Ettinger M, Ezechieli M. et al. Repair of retropatellar cartilage defects in the knee with microfracture and a cell-free polymer-based implant. Arch Orthop Trauma Surg 2015; 135: 1003-1010 doi:10.1007/s00402-015-2235-5
• 50 Enea D, Cecconi S, Calcagno S. et al. Single-stage cartilage repair in the knee with microfracture covered with a resorbable polymer-based matrix and autologous bone marrow concentrate. Knee 2013; 20: 562-569 doi:10.1016/j.knee.2013.04.003
• 51 Siclari A, Mascaro G, Kaps C. et al. A 5-year follow-up after cartilage repair in the knee using a platelet-rich plasma-immersed polymer-based implant. Open Orthop J 2014; 8: 346-354 doi:10.2174/1874325001408010346
• 52 Buda R, Vannini F, Cavallo M. et al. Osteochondral lesions of the knee: a new one-step repair technique with bone-marrow-derived cells. J Bone Joint Surg Am 2010; 92 (Suppl. 02) S2-S11 doi:10.2106/JBJS.J.00813
• 53 Gobbi A, Scotti C, Karnatzikos G. et al. One-step surgery with multipotent stem cells and Hyaluronan-based scaffold for the treatment of full-thickness chondral defects of the knee in patients older than 45 years. Knee Surg Sports Traumatol Arthrosc 2017; 25: 2494-2501 doi:10.1007/s00167-016-3984-6
• 54 Gobbi A, Whyte GP. One-stage cartilage repair using a hyaluronic acid-based scaffold with activated bone marrow-derived mesenchymal stem cells compared with microfracture. Am J Sports Med 2016; 44: 2846-2854 doi:10.1177/0363546516656179
• 55 Sofu H, Kockara N, Oner A. et al. Results of hyaluronic acid–based cell-free scaffold application in combination with microfracture for the treatment of osteochondral lesions of the knee: 2-year comparative study. Arthroscopy 2017; 33: 209-216 doi:10.1016/j.arthro.2016.06.035
• 56 Vannini F, Battaglia M, Buda R. et al. “One step” treatment of juvenile osteochondritis dissecans in the knee: clinical results and T2 mapping characterization. Orthop Clin North Am 2012; 43: 237-244 doi:10.1016/j.ocl.2012.02.003
• 57 Enea D, Cecconi S, Calcagno S. et al. One-step cartilage repair in the knee: collagen-covered microfracture and autologous bone marrow concentrate. A pilot study. Knee 2015; 22: 30-35 doi:10.1016/j.knee.2014.10.003
• 58 Gigante A, Calcagno S, Cecconi S. et al. Use of collagen scaffold and autologous bone marrow concentrate as a one-step cartilage repair in the knee: histological results of second-look biopsies at 1 year follow-up. Int J Immunopathol Pharmacol 2011; 24 (1 Suppl.  2): S69-S72
• 59 Berruto M, Delcogliano M, de Caro F. et al. Treatment of large knee osteochondral lesions with a biomimetic scaffold: results of a multicenter study of 49 patients at 2-year follow-up. Am J Sports Med 2014; 42: 1607-1617
• 60 Brix M, Kaipel M, Kellner R. et al. Successful osteoconduction but limited cartilage tissue quality following osteochondral repair by a cell-free multilayered nano-composite scaffold at the knee. Int Orthop 2016; 40: 625-632 doi:10.1007/s00264-016-3118-2
• 61 Christensen BB, Foldager CB, Jensen J. et al. Poor osteochondral repair by a biomimetic collagen scaffold: 1- to 3-year clinical and radiological follow-up. Knee Surg Sports Traumatol Arthrosc 2016; 24: 2380-2387 doi:10.1007/s00167-015-3538-3
• 62 Delcogliano M, de Caro F, Scaravella E. et al. Use of innovative biomimetic scaffold in the treatment for large osteochondral lesions of the knee. Knee Surg Sports Traumatol Arthrosc 2014; 22: 1260-1269 doi:10.1007/s00167-013-2717-3
• 63 Delcogliano M, Menghi A, Placella G. et al. Treatment of osteochondritis dissecans of the knee with a biomimetic scaffold. A prospective multicenter study. Joints 2014; 2: 102-108
• 64 Perdisa F, Filardo G, Sessa A. et al. One-step treatment for patellar cartilage defects with a cell-free osteochondral scaffold: a prospective clinical and MRI evaluation. Am J Sports Med 2017; 45: 1581-1588 doi:10.1177/0363546517694159
• 65 Pot MW, Gonzales VK, Buma P. et al. Improved cartilage regeneration by implantation of acellular biomaterials after bone marrow stimulation: a systematic review and meta-analysis of animal studies. PeerJ 2016; 4: e2243 doi:10.7717/peerj.2243
• 66 Chu C, Szczodry M, Bruno S. Animal models for cartilage regeneration and repair. Tissue Eng Part B Rev 2010; 16: 105-115
• 67 Beck A, Murphy DJ, Carey-Smith R. et al. Treatment of articular cartilage defects with microfracture and autologous matrix-induced chondrogenesis leads to extensive subchondral bone cyst formation in a sheep model. Am J Sports Med 2016; 44: 2629-2643 doi:10.1177/0363546516652619
• 68 Roessler P, Pfister B, Gesslein M. et al. Short-term follow up after implantation of a cell-free collagen type I matrix for the treatment of large cartilage defects of the knee. Int Orthop 2015; 39: 2473-2479
• 69 Kusano T, Jacobi M, Hoogewoud HM. et al. Paper 143: Autologous Matrix-Induced Chondrogenesis (AMIC) – treatment of chondral and osteochondral defects in the knee. Arthroscopy 2012; 28: e419-e420 doi:10.1016/j.arthro.2012.05.626
• 70 Hasson F, Keeney S, McKenna H. Research guidelines for the Delphi survey technique. J Adv Nurs 2000; 32: 1008-1015 doi:10.1046/j.1365-2648.2000.t01-1-01567.x
• 71 Hirschmüller A, Baur H, Braun S. et al. Rehabilitation after autologous chondrocyte implantation for isolated cartilage defects of the knee. Am J Sports Med 2011; 39: 2686-2696 doi:10.1177/0363546511404204
• 72 Mithoefer K, Hambly K, Logerstedt D. et al. Current concepts for rehabilitation and return to sport after knee articular cartilage repair in the athlete. J Orthop Sports Phys Ther 2012; 42: 254-273 doi:10.2519/jospt.2012.3665
• 73 Keller M, Kurz E, Schmidtlein O. et al. [Interdisciplinary assessment criteria for rehabilitation after injuries of the lower extremity: a function-based return to activity algorithm]. Sportverletz Sportschaden 2016; 30: 38-49 doi:10.1055/s-0042-100966
• 74 Aurich M, Albrecht D, Angele P. et al. [Treatment of Osteochondral Lesions in the Ankle: A Guideline from the Group “Clinical Tissue Regeneration” of the German Society of Orthopaedics and Traumatology (DGOU)]. Z Orthop Unfall 2017; 155: 92-99 doi:10.1055/s-0042-116330
• 75 Fickert S, Aurich M, Albrecht D. et al. [Biologic Reconstruction of Full Sized Cartilage Defects of the Hip: A Guideline from the DGOU Group “Clinical Tissue Regeneration” and the Hip Committee of the AGA]. Z Orthop Unfall 2017; 155: 670-682 doi:10.1055/s-0043-116218