Microfractures Versus a Porcine-Derived Collagen-Augmented Chondrogenesis Technique for Treating Knee Cartilage Defects: A Multicenter Randomized Controlled Trial

Published:November 27, 2019DOI:


      The purpose of this study was to evaluate the clinical efficacy and safety of treating patients with a cartilage defect of the knee with microfractures and porcine-derived collagen-augmented chondrogenesis technique (C-ACT).


      One hundred participants were randomly assigned to the control group (n = 48, microfracture) or the investigational group (n = 52, C-ACT). Clinical and magnetic resonance imaging (MRI) outcomes were assessed 12 and 24 months postoperatively for efficacy and adverse events. Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) assessment was used to analyze cartilage tissue repair. MRI outcomes for 50% defect filling and repaired tissue/reference cartilage (RT/RC) ratio were quantified using T2 mapping. Clinical outcomes were assessed using the visual analogue scale (VAS) for pain and 20% improvement, minimal clinically important difference (MCID), and patient acceptable symptom state for Knee Injury and Osteoarthritis Outcome Score (KOOS) and the International Knee Documentation Committee score.


      MOCART scores in the investigation group showed improved defect repair and filling (P = .0201), integration with the border zone (P = .0062), and effusion (P = .0079). MRI outcomes showed that the odds ratio (OR) for ≥50% defect filling at 12 months was statistically higher in the investigation group (OR 3.984, P = .0377). Moreover, the likelihood of the RT/RC OR becoming ≥1 was significantly higher (OR 11.37, P = .0126) in the investigation group. At 24 months postoperatively, the OR for the VAS 20% improvement rate was significantly higher in the investigational group (OR 2.808, P = .047). Twenty-three patients (52.3%) in the control group and 35 (77.8%) in the investigation group demonstrated more than the MCID of KOOS pain from baseline to 1 year postoperatively, with a significant difference between groups (P = .0116).


      In this multicenter randomized trial, the addition of C-ACT resulted in better filling of cartilage defect of the knee joint.

      Level of Evidence

      Level Ⅰ, Multicenter Randomized Controlled Trial
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Arthroscopy
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Seo S.S.
        • Kim C.W.
        • Jung D.W.
        Management of focal chondral lesion in the knee joint.
        Knee Surg Relat Res. 2011; 23: 185-196
        • Williams III, R.J.
        • Brophy R.H.
        Cartilage repair procedures: clinical approach and decision making.
        Instr Course Lect. 2008; 57: 553-561
        • Filardo G.
        • Kon E.
        • Roffi A.
        • Di Martino A.
        • Marcacci M.
        Scaffold-based repair for cartilage healing: a systematic review and technical note.
        Arthroscopy. 2013; 29: 174-186
        • Mithoefer K.
        • McAdams T.
        • Williams R.J.
        • Kreuz P.C.
        • Mandelbaum B.R.
        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
        • Kim J.K.
        • Vaidya R.
        • Lee S.K.
        • et al.
        Clinical and radiological changes after microfracture of knee chondral lesions in middle-aged asian patients.
        Clin Orthop Surg. 2019; 11: 282-290
        • Kim M.S.
        • Koh I.J.
        • Choi Y.J.
        • Pak K.H.
        • In Y.
        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
        • Stelzeneder D.
        • Shetty A.A.
        • Kim S.J.
        • et al.
        Repair tissue quality after arthroscopic autologous collagen-induced chondrogenesis (ACIC) assessed via T2* mapping.
        Skeletal Radiol. 2013; 42: 1657-1664
        • Volpi P.
        • Bait C.
        • Quaglia A.
        • et al.
        Autologous collagen-induced chondrogenesis technique (ACIC) for the treatment of chondral lesions of the talus.
        Knee Surg Sports Traumatol Arthrosc. 2014; 22: 1320-1326
        • Di Lullo G.A.
        • Sweeney S.M.
        • Korkko J.
        • Ala-Kokko L.
        • San Antonio J.D.
        Mapping the ligand-binding sites and disease-associated mutations on the most abundant protein in the human, type I collagen.
        J Biol Chem. 2002; 277: 4223-4231
        • Mimura T.
        • Imai S.
        • Kubo M.
        • et al.
        A novel exogenous concentration-gradient collagen scaffold augments full-thickness articular cartilage repair.
        Osteoarthritis Cartilage. 2008; 16: 1083-1091
        • Sinani V.A.
        • Koktysh D.S.
        • Yun B.-G.
        • et al.
        Collagen coating promotes biocompatibility of semiconductor nanoparticles in stratified LBL films.
        Nano Lett. 2003; 3: 1177-1182
        • Anders S.
        • Volz M.
        • Frick H.
        • Gellissen J.
        A randomized, controlled trial comparing autologous matrix-induced chondrogenesis (AMIC(R)) to microfracture: Analysis of 1- and 2-year follow-up data of 2 centers.
        Open Orthop J. 2013; 7: 133-143
        • Volz M.
        • Schaumburger J.
        • Frick H.
        • Grifka J.
        • Anders S.
        A randomized controlled trial demonstrating sustained benefit of autologous matrix-induced chondrogenesis over microfracture at five years.
        Int Orthop. 2017; 41: 797-804
        • Usuelli F.G.
        • Grassi M.
        • Manzi L.
        • Guarrella V.
        • Boga M.
        • L D.E.G.
        Treatment of osteochondral lesions of the talus with autologous collagen-induced chondrogenesis: Clinical and magnetic resonance evaluation at one-year follow-up.
        Joints. 2016; 4: 80-86
        • Dugdale T.W.
        • Noyes F.R.
        • Styer D.
        Preoperative planning for high tibial osteotomy. The effect of lateral tibiofemoral separation and tibiofemoral length.
        Clin Orthop Relat Res. 1992; : 248-264
        • Fujisawa Y.
        • Masuhara K.
        • Shiomi S.
        The effect of high tibial osteotomy on osteoarthritis of the knee. An arthroscopic study of 54 knee joints.
        Orthop Clin North Am. 1979; 10: 585-608
        • Goebel L.
        • Orth P.
        • Muller A.
        • et al.
        Experimental scoring systems for macroscopic articular cartilage repair correlate with the MOCART score assessed by a high-field MRI at 9.4 T—Comparative evaluation of five macroscopic scoring systems in a large animal cartilage defect model.
        Osteoarthritis Cartilage. 2012; 20: 1046-1055
        • Marlovits S.
        • Singer P.
        • Zeller P.
        • Mandl I.
        • Haller J.
        • Trattnig S.
        Magnetic resonance observation of cartilage repair tissue (MOCART) for the evaluation of autologous chondrocyte transplantation: Determination of interobserver variability and correlation to clinical outcome after 2 years.
        Eur J Radiol. 2006; 57: 16-23
        • Choi Y.S.
        • Potter H.G.
        • Chun T.J.
        MR imaging of cartilage repair in the knee and ankle.
        Radiographics. 2008; 28: 1043-1059
        • Henderson I.J.
        • Tuy B.
        • Connell D.
        • Oakes B.
        • Hettwer W.H.
        Prospective clinical study of autologous chondrocyte implantation and correlation with MRI at three and 12 months.
        J Bone Joint Surg Br. 2003; 85: 1060-1066
        • Crema M.D.
        • Roemer F.W.
        • Marra M.D.
        • et al.
        Articular cartilage in the knee: Current MR imaging techniques and applications in clinical practice and research.
        Radiographics. 2011; 31: 37-61
        • Mamisch T.C.
        • Trattnig S.
        • Quirbach S.
        • Marlovits S.
        • White L.M.
        • Welsch G.H.
        Quantitative T2 mapping of knee cartilage: Differentiation of healthy control cartilage and cartilage repair tissue in the knee with unloading—Initial results.
        Radiology. 2010; 254: 818-826
        • Domayer S.E.
        • Kutscha-Lissberg F.
        • Welsch G.
        • et al.
        T2 mapping in the knee after microfracture at 3.0 T: Correlation of global T2 values and clinical outcome—Preliminary results.
        Osteoarthritis Cartilage. 2008; 16: 903-908
        • Freitag J.
        • Shah K.
        • Wickham J.
        • Boyd R.
        • Tenen A.
        The effect of autologous adipose derived mesenchymal stem cell therapy in the treatment of a large osteochondral defect of the knee following unsuccessful surgical intervention of osteochondritis dissecans—A case study.
        BMC Musculoskelet Disord. 2017; 18: 298
        • Roos E.M.
        • Roos H.P.
        • Lohmander L.S.
        • Ekdahl C.
        • Beynnon B.D.
        Knee Injury and Osteoarthritis Outcome Score (KOOS)—Development of a self-administered outcome measure.
        J Orthop Sports Phys Ther. 1998; 28: 88-96
        • Rossi M.J.
        • Lubowitz J.H.
        • Guttmann D.
        Development and validation of the International Knee Documentation Committee Subjective Knee Form.
        Am J Sports Med. 2002; 30: 152
        • Salottolo K.
        • Stahl E.
        Minimal clinically important improvement response in patients with severe osteoarthritis of the knee: Short report from a survey of clinicians.
        J Orthop. 2018; 15: 424-425
        • Harris J.D.
        • Brand J.C.
        • Cote M.P.
        • Faucett S.C.
        • Dhawan A.
        The significance of statistics and perils of pooling. Part 1: Clinical versus statistical significance.
        Arthroscopy. 2017; 33: 1102-1112
        • Kelly A.M.
        The minimum clinically significant difference in visual analogue scale pain score does not differ with severity of pain.
        Emerg Med J. 2001; 18: 205-207
        • Crawford D.C.
        • DeBerardino T.M.
        • Williams 3rd, R.J.
        NeoCart, an autologous cartilage tissue implant, compared 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
        • Stanish W.D.
        • McCormack R.
        • Forriol F.
        • et al.
        Novel scaffold-based BST-CarGel treatment results in superior cartilage repair compared with microfracture in a randomized controlled trial.
        J Bone Joint Surg Am. 2013; 95: 1640-1650
        • Gelse K.
        • Pöschl E.
        • Aigner T.
        Collagens—Structure, function, and biosynthesis.
        Advanced Drug Deliv Rev. 2003; 55: 1531-1546
        • Burgeson R.E.
        • Nimni M.E.
        Collagen types. Molecular structure and tissue distribution.
        Clin Orthop Relat Res. 1992; : 250-272
        • Chevallay B.
        • Herbage D.
        Collagen-based biomaterials as 3D scaffold for cell cultures: Applications for tissue engineering and gene therapy.
        Med Biol Eng Comput. 2000; 38: 211-218
        • Wolf K.
        • Alexander S.
        • Schacht V.
        • et al.
        Collagen-based cell migration models in vitro and in vivo.
        Semin Cell Dev Biol. 2009; 20: 931-941
        • Tubach F.
        • Ravaud P.
        • Baron G.
        • et al.
        Evaluation of clinically relevant changes in patient reported outcomes in knee and hip osteoarthritis: The minimal clinically important improvement.
        Ann Rheum Dis. 2005; 64: 29-33
        • Marik W.
        • Apprich S.
        • Welsch G.H.
        • Mamisch T.C.
        • Trattnig S.
        Biochemical evaluation of articular cartilage in patients with osteochondrosis dissecans by means of quantitative T2- and T2-mapping at 3T MRI: A feasibility study.
        Eur J Radiol. 2012; 81: 923-927
        • Welsch G.H.
        • Apprich S.
        • Zbyn S.
        • et al.
        Biochemical (T2, T2* and magnetisation transfer ratio) MRI of knee cartilage: Feasibility at ultra-high field (7T) compared with high field (3T) strength.
        Eur Radiol. 2011; 21: 1136-1143
        • Welsch G.H.
        • Trattnig S.
        • Hughes T.
        • et al.
        T2 and T2* mapping in patients after matrix-associated autologous chondrocyte transplantation: Initial results on clinical use with 3.0-Tesla MRI.
        Eur Radiol. 2010; 20: 1515-1523
        • Knutsen G.
        • Drogset J.O.
        • Engebretsen L.
        • et al.
        A randomized trial comparing autologous chondrocyte implantation with microfracture: Findings at five years.
        J Bone Joint Surg Am. 2007; 89: 2105-2112
        • Welsch G.H.
        • Hennig F.F.
        • Krinner S.
        • Trattnig S.
        T2 and T2* mapping.
        Curr Radiol Reports. 2014; 2: 60
        • Mamisch T.C.
        • Hughes T.
        • Mosher T.J.
        • et al.
        T2 star relaxation times for assessment of articular cartilage at 3 T: A feasibility study.
        Skeletal Radiol. 2012; 41: 287-292
        • Welsch G.H.
        • Mamisch T.C.
        • Domayer S.E.
        • et al.
        Cartilage T2 assessment at 3-T MR imaging: In vivo differentiation of normal hyaline cartilage from reparative tissue after two cartilage repair procedures—Initial experience.
        Radiology. 2008; 247: 154-161
        • Welsch G.H.
        • Trattnig S.
        • Scheffler K.
        • et al.
        Magnetization transfer contrast and T2 mapping in the evaluation of cartilage repair tissue with 3T MRI.
        J Magn Reson Imaging. 2008; 28: 979-986
        • Neel E.A.A.
        • Bozec L.
        • Knowles J.C.
        • et al.
        Collagen—Emerging collagen based therapies hit the patient.
        Adv Drug Deliv Rev. 2013; 65: 429-456
        • Kuznetsova N.
        • Leikin S.
        Does the triple helical domain of type I collagen encode molecular recognition and fiber assembly while telopeptides serve as catalytic domains? Effect of proteolytic cleavage on fibrillogenesis and on collagen-collagen interaction in fibers.
        J Biol Chem. 1999; 274: 36083-36088
        • Yang C.
        • Hillas P.J.
        • Baez J.A.
        • et al.
        The application of recombinant human collagen in tissue engineering.
        BioDrugs. 2004; 18: 103-119
        • Kim J.
        • Cho H.
        • Young K.
        • Park J.
        • Lee J.
        • Suh D.
        In vivo animal study and clinical outcomes of autologous atelocollagen-induced chondrogenesis for osteochondral lesion treatment.
        J Orthop Surg Res. 2015; 10: 82

      Linked Article

      • Editorial Commentary: Cartilage Restoration—What Is Currently Available?
        ArthroscopyVol. 36Issue 6
        • Preview
          In the past 30 years, bone marrow stimulation techniques such as microfracture (MF) have become a popular method to treat symptomatic focal articular cartilage lesions. Nonetheless, recent studies have not shown good long-term clinical outcomes, and MF has produced alterations in the subchondral bone architecture with degenerative changes. Autologous chondrocyte implantation (ACI) has shown good results at 20 years. Second- and third-generation ACI has shown superiority to MF and fewer complications than first-generation ACI.
        • Full-Text
        • PDF