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The Most Common Rehabilitation Protocol After Matrix-Assisted Autologous Chondrocyte Implantation Is Immediate Partial Weight-Bearing and Continuous Passive Motion

Open AccessPublished:November 18, 2022DOI:https://doi.org/10.1016/j.asmr.2022.09.007

      Purpose

      To perform a systematic review of postoperative rehabilitation protocols for third-generation autologous chondrocyte implantation (ACI) of the knee joint.

      Methods

      A systematic review was performed by searching PubMed, Cochrane Library, and EMBASE to locate randomized controlled trials that described a rehabilitation protocol following third-generation ACI of the knee joint. The search terms used were: “autologous” AND “chondrocyte” AND “randomized”. Data extracted from each study included various components of postoperative rehabilitation, such as initial weight-bearing (WB) status and time to full WB, the use of continuous passive motion (CPM), the time to return to sports, and physical therapy (PT) modalities used and the timing of their initiation.

      Results

      Twenty-five studies (22 Level I, 3 Level II) met inclusion criteria, including a total of 905 patients undergoing treatment with ACI. The average patient age ranged from 29.1 to 54.8 years, and the mean follow-up time ranged from 3 months to 10.0 years. The average lesion size ranged from 1.9 to 5.8 cm2, and the most common lesion location was the medial femoral condyle (n = 494). Twenty studies allowed partial WB postoperatively with all studies permitting full WB within 12 weeks. Twenty studies used CPM in their rehabilitation protocols and initiated its use within 24 hours postoperatively. Among 10 studies that reported time to return to sport, 9 (90%) allowed return by 12 months. While most protocols used strength training as well as the inclusion of proprioceptive training, there was disagreement on the timing and inclusion of specific PT modalities used during the rehabilitation process.

      Conclusions

      Based on the included studies, most rehabilitation protocols for third-generation ACI initiate CPM within 24 hours postoperatively and allow partial WB immediately following surgery with progression to full WB within 12 weeks. There is variation of the PT modalities used as well as the timing of their initiation.

      Level of Evidence

      Level II, systematic review of Level I-II studies.
      Focal chondral defects (FCDs) of the knee joint can result in pain and swelling and may become especially disruptive to active patients and athletes.
      • Chubinskaya S.
      • Haudenschild D.
      • Gasser S.
      • Stannard J.
      • Krettek C.
      • Borrelli Jr., J.
      Articular cartilage injury and potential remedies.
      Cartilage defects are challenging to treat, given the avascularity of articular cartilage and the multiple factors that affect cartilage health, including meniscal status, limb alignment, and ligament stability.
      • Dekker T.J.
      • Aman Z.S.
      • DePhillipo N.N.
      • Dickens J.F.
      • Anz A.W.
      • LaPrade R.F.
      Chondral lesions of the knee: An evidence-based approach.
      Current surgical treatments for FCDs of the knee joint include chondroplasty, microfracture (MFx), osteochondral autograft transfer (OAT), osteochondral allograft transplantation (OCA), and autologous chondrocyte implantation (ACI), among others.
      • Schrock J.B.
      • Kraeutler M.J.
      • Houck D.A.
      • McQueen M.B.
      • McCarty E.C.
      A cost-effectiveness analysis of surgical treatment modalities for chondral lesions of the knee: Microfracture, osteochondral autograft transplantation, and autologous chondrocyte implantation.
      ACI, which is a 2-stage procedure, is now in its third-generation form, which is otherwise known as matrix-assisted ACI.
      • Schuette H.B.
      • Kraeutler M.J.
      • McCarty E.C.
      Matrix-assisted autologous chondrocyte transplantation in the knee: A systematic review of mid- to long-term clinical outcomes.
      Third-generation ACI involves taking a biopsy of healthy articular cartilage during the first-stage procedure, followed 6 to 8 weeks later by implantation of a matrix scaffold seeded with autologous chondrocytes.
      • Schuette H.B.
      • Kraeutler M.J.
      • McCarty E.C.
      Matrix-assisted autologous chondrocyte transplantation in the knee: A systematic review of mid- to long-term clinical outcomes.
      Given that third-generation ACI is a relatively novel procedure, postoperative rehabilitation following this procedure is not standardized.
      • Kraeutler M.J.
      • Belk J.W.
      • Carver T.J.
      • McCarty E.C.
      Is delayed weightbearing after matrix-associated autologous chondrocyte implantation in the knee associated with better outcomes? A systematic review of randomized controlled trials.
      In a 2018 systematic review, Kraeutler et al.
      • Kraeutler M.J.
      • Belk J.W.
      • Carver T.J.
      • McCarty E.C.
      Is delayed weightbearing after matrix-associated autologous chondrocyte implantation in the knee associated with better outcomes? A systematic review of randomized controlled trials.
      compared treatment failure rates and other clinical outcomes of matrix-assisted ACI based on the time to return to full weight-bearing (WB). However, this is just one aspect of postoperative rehabilitation, and other aspects, such as the use of continuous passive motion (CPM) and criteria for return-to-play (RTP), are equally important in determining a patient’s overall outcome and satisfaction. The purpose of this study was to perform a systematic review of postoperative rehabilitation protocols for third-generation ACI of the knee joint. The authors hypothesized that there would be heterogeneity in the postoperative rehabilitation protocols reported in the literature.

      Methods

      This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Two independent reviewers (J.D., S.M.F.) searched PubMed, Embase, and the Cochrane Library up to January 17, 2022. The electronic search strategy used was: autologous AND chondrocyte AND randomized. A total of 652 studies were reviewed by title and/or abstract to determine study eligibility based on inclusion criteria. In cases of disagreement, a third reviewer (M.J.K.) made the final decision. Inclusion criteria included randomized controlled trials that reported their rehabilitation protocol after third-generation ACI for FCDs of the knee joint. Studies were excluded if they were nonrandomized, studies on first- or second-generation ACI, nonhuman studies, non-knee joint studies, the rehabilitation protocol was not reported, or no English full-text article was available. Data extraction from each study was performed independently by 2 authors (J.D., S.M.F.) and then reviewed by a third author (M.J.K.). There was no need for funding or a third party to obtain any of the collected data. Risk of bias was assessed according to the Cochrane Collaboration’s risk of bias tool,
      • Higgins J.P.
      • Altman D.G.
      • Gøtzsche P.C.
      • et al.
      The Cochrane Collaboration's tool for assessing risk of bias in randomised trials.
      which incorporates an assessment of randomization, blinding, completeness of outcomes data, selection of outcomes reported, and other sources of bias.

      Study Methodology Assessment

      The Modified Coleman Methodology Score (MCMS)
      • Coleman B.D.
      • Khan H.M.
      • Maffulli N.
      • Cook J.L.
      • Wark J.D.
      Studies of surgical outcome after patellar tendinopathy: clinical significance of methodological deficiencies and guidelines for future studies. Victorian Institute of Sport Tendon Study Group.
      was used to evaluate study methodology quality. The MCMS has a scaled potential score ranging from 0 to 100. Scores ranging from 85 to 100 are excellent, 70 to 84 are good, 55 to 69 are fair, and less than 55 are poor. The primary outcomes assessed by the MCMS are study size and type, follow-up time, attrition rates, number of interventions per group, and proper description of study methodology.

      Data Extraction

      Data extracted from each study included the various components of postoperative rehabilitation, such as initial WB status and time to full WB, the use of CPM, the time to RTP, and physical therapy modalities used and the timing of their initiation.

      Results

      Twenty-five studies met inclusion and exclusion criteria (Fig 1), including a total of 905 patients undergoing treatment with ACI. The mean patient age ranged from 29.1 to 54.8 years and the mean follow-up ranged from 3 months to 10.0 years. The overall percentage of male subjects ranged from 44.4% to 74.2% and the mean body mass index ranged from 23.3 to 29.0 (Table 1). The mean lesion size ranged from 1.9 to 5.8 cm2. The most common lesion location was the medial femoral condyle (n = 494 cases) followed by the lateral femoral condyle (n = 167 cases). Six studies
      • Brittberg M.
      • Recker D.
      • Ilgenfritz J.
      • Saris D.B.F.
      SUMMIT Extension Study Group. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: Five-year follow-up of a prospective randomized trial.
      • Ebert J.R.
      • Edwards P.K.
      • Fallon M.
      • Ackland T.R.
      • Janes G.C.
      • Wood D.J.
      Two-year outcomes of a randomized trial investigating a 6-week return to full weightbearing after matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      • 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.
      • Wondrasch B.
      • Risberg M.A.
      • Zak L.
      • Marlovits S.
      • Aldrian S.
      Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle: a prospective, randomized controlled study presenting MRI-based and clinical outcomes after 5 years.
      • Wondrasch B.
      • Zak L.
      • Welsch G.H.
      • 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.
      presented 2 of the same patient populations and therefore only the studies with longer follow-up
      • Brittberg M.
      • Recker D.
      • Ilgenfritz J.
      • Saris D.B.F.
      SUMMIT Extension Study Group. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: Five-year follow-up of a prospective randomized trial.
      ,
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      ,
      • Wondrasch B.
      • Risberg M.A.
      • Zak L.
      • Marlovits S.
      • Aldrian S.
      Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle: a prospective, randomized controlled study presenting MRI-based and clinical outcomes after 5 years.
      were included in the results of our systematic review.
      Figure thumbnail gr1
      Fig 1PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram. (ACI, autologous chondrocyte implantation.)
      Table 1Patient Demographics
      StudyLOENMale, %Age at Surgery, yBMIFollow-up, yDefect Size, cm2Lesion LocationAuthor CountryType of ACI Product
      Akgun et al., 2015
      • Akgun I.
      • Unlu M.C.
      • Erdal O.A.
      • et al.
      Matrix-induced autologous mesenchymal stem cell implantation versus matrix-induced autologous chondrocyte implantation in the treatment of chondral defects of the knee: A 2-year randomized study.
      I75732.7 ± 10.424.3 ± 0.823.0 ± 0.8MFC: 5; LFC: 2TurkeyChondro-Gide
      Barié et al., 2020
      • Barié A.
      • Kruck P.
      • Sorbi R.
      • et al.
      Prospective long-term follow-up of autologous chondrocyte implantation with periosteum versus matrix-associated autologous chondrocyte implantation: A randomized clinical trial.
      I944.430.4 ± 6.823.32 ± 1.159.6 ± 0.94.27 ± 0.2MFC: 8; LFC: 1GermanyBioSeed-C
      Basad et al., 2010
      • Basad E.
      • Ishaque B.
      • Bachmann G.
      • Stürz H.
      • Steinmeyer J.
      Matrix-induced autologous chondrocyte implantation versus microfracture in the treatment of cartilage defects of the knee: A 2-year randomised study.
      I4063.033.025.32NRC: 29; PT: 11GermanyACI-Maix
      Saris et al., 2014
      • 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.


      Brittberg et al., 2018
      • Brittberg M.
      • Recker D.
      • Ilgenfritz J.
      • Saris D.B.F.
      SUMMIT Extension Study Group. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: Five-year follow-up of a prospective randomized trial.
      I7262.534.8 ± 9.226.2 ± 4.325.8 ± 5.1MFC: 48; LFC: 13; T: 4Netherlands/ SwedenACI-Maix
      Clavé et al., 2016
      • Clavé A.
      • Potel J.F.
      • Servien E.
      • et al.
      Third-generation autologous chondrocyte implantation versus mosaicplasty for knee cartilage injury: 2-year randomized trial.
      I3066.729.2 ± 11.923.4 ± 3.123.1 ± 0.8NRFranceCartipatch
      Crawford et al., 2012
      • 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.
      I2190.041 ± 929 ± 322.9 ± 1.4NRU.S.A.NeoCart
      Ebert et al., 2008
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      Traditional vs accelerated approaches to post-operative rehabilitation following matrix-induced autologous chondrocyte implantation (MACI): Comparison of clinical, biomechanical and radiographic outcomes.
      I6264.538.3NR3 months3.3MFC: 45; LFC: 17AustraliaACI-Maix
      Ebert et al., 2010
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      A prospective, randomized comparison of traditional and accelerated approaches to postoperative rehabilitation following autologous chondrocyte implantation: 2-year clinical outcomes.
      I7064.338.2NR23.3MFC: 52; LFC: 18AustraliaACI-Maix
      Ebert et al., 2010
      • Ebert J.R.
      • Lloyd D.G.
      • Ackland T.
      • Wood D.J.
      Knee biomechanics during walking gait following matrix-induced autologous chondrocyte implantation.
      I6163.938.5NR13.3MFC: 46; LFC 15AustraliaACI-Maix
      Ebert et al., 2011
      • Ebert J.R.
      • Fallon M.
      • Robertson W.B.
      • et al.
      Radiological assessment of accelerated versus traditional approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation.
      I6963.838.226.623.3MFC: 52; LFC: 17AustraliaACI-Maix
      Ebert et al., 2012
      • Ebert J.R.
      • Fallon M.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.R.
      A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: Findings at 5 years.
      I6366.738.226.553.3MFC: 47; LFC: 16AustraliaACI-Maix
      Ebert et al., 2020
      • Ebert J.R.
      • Fallon M.
      • Ackland T.R.
      • Janes G.C.
      • Wood D.J.
      Minimum 10-year clinical and radiological outcomes of a randomized controlled trial evaluating 2 different approaches to full weightbearing after matrix-induced autologous chondrocyte implantation.
      I6065.037.627.5103.27MFC: 44; LFC: 16AustraliaACI-Maix
      Ebert et al., 2021
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.


      Ebert et al., 2017
      • Ebert J.R.
      • Edwards P.K.
      • Fallon M.
      • Ackland T.R.
      • Janes G.C.
      • Wood D.J.
      Two-year outcomes of a randomized trial investigating a 6-week return to full weightbearing after matrix-induced autologous chondrocyte implantation.
      I3756.836.425.753.0MFC: 27; LFC: 10AustraliaACI-Maix
      Edwards et al., 2013
      • Edwards P.K.
      • Ackland T.R.
      • Ebert J.R.
      Accelerated weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint: Early clinical and radiological outcomes.
      I2860.735.825.612.9MFC: 20; LFC: 8AustraliaACI-Maix
      Fossum et al., 2019
      • Fossum V.
      • Hansen A.K.
      • Wilsgaard T.
      • Knutsen G.
      Collagen-covered autologous chondrocyte implantation versus autologous matrix-induced chondrogenesis: A randomized trial comparing 2 methods for repair of cartilage defects of the knee.
      II2166.737.2 ± 10.825.7 ± 4.324.9 ± 4.4MFC: 7; LFC:2; T: 7; P: 1; PT: 2; T-MFC: 2NorwayChondro-Gide
      Hoburg et al., 2021
      • Hoburg A.
      • Niemeyer P.
      • Laute V.
      • et al.
      Matrix-associated autologous chondrocyte implantation with spheroid technology is superior to arthroscopic microfracture at 36 months regarding activities of daily living and sporting activities after treatment.
      I5263.536 ± 1025.7 ± 3.332.2 ± 0.7C: 52GermanySpherox
      Ibarra et al., 2021
      • Ibarra C.
      • Villalobos E.
      • Madrazo-Ibarra A.
      • et al.
      Arthoscopic matrix-assisted autologous chondrocyte transplantation versus microfracture: A 6-year follow-up of a prospective randomized trial.
      I2470.833.7 ± 9.425.5 ± 3.16.2 ± 0.91.9 ± 0.9MFC: 7: LFC: 9; T: 1; P: 7MexicoNeoveil
      Liu et al., 2021
      • Liu Y.L.
      • Yen C.C.
      • Liu T.T.
      • et al.
      Safety and efficacy of Kartigen® in treating cartilage defects: A randomized, controlled, phase I trial.
      I105054.8 ± 18.0NR1.12.9 ± 0.8MFC: 10TaiwanKartigen
      Niemeyer et al., 2019
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      A prospective, randomized, open-label, multicenter, Phase III noninferiority trial to compare the clinical efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology versus arthroscopic microfracture for cartilage defects of the knee.
      II5263.436 ± 1025.7 ± 3.322.2 ± 0.7C: 52GermanySpherox
      Niemeyer et al., 2020
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      Safety and efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology is independent of spheroid dose after 4 years.
      I7570.733.5 ± 9.225.2 ± 3.145.0 ± 1.9C: 28; P: 47GermanySpherox
      Wondrasch et al 2009
      • Wondrasch B.
      • Zak L.
      • Welsch G.H.
      • 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.


      Wondrasch et al. 2015
      • Wondrasch B.
      • Risberg M.A.
      • Zak L.
      • Marlovits S.
      • Aldrian S.
      Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle: a prospective, randomized controlled study presenting MRI-based and clinical outcomes after 5 years.
      I3174.23324.724.8MFC: 22; LFC: 10AustriaHyalograftC
      Zeifang et al., 2010
      • Zeifang F.
      • Oberle D.
      • Nierhoff C.
      • et al.
      Autologous chondrocyte implantation using the original periosteum-cover technique versus matrix-associated autologous chondrocyte implantation: A randomized clinical trial.
      II1154.529.1 ± 7.5NR24.3 ± 1.1NRGermanyBioSeed-C
      NOTE. Only the nonoverlapping patient samples are included to avoid redundancy. Sex is reported as a percentage. Age, BMI, follow-up, and defect size are reported as mean ± SD (if available).
      ACI, autologous chondrocyte implantation; BMI, body mass index; C, nonspecified femoral condyle; LFC, lateral femoral condyle; LOE, Level of Evidence; MFC, medial femoral condyle; N, number of lesions; NR, not reported, P, patella; PT, patella-trochlea; SD, standard deviation; T, trochlea; T-MFC, trochlea and medial femoral condyle.

      Postoperative WB

      Twenty-two studies
      • Brittberg M.
      • Recker D.
      • Ilgenfritz J.
      • Saris D.B.F.
      SUMMIT Extension Study Group. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: Five-year follow-up of a prospective randomized trial.
      ,
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      ,
      • Wondrasch B.
      • Risberg M.A.
      • Zak L.
      • Marlovits S.
      • Aldrian S.
      Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle: a prospective, randomized controlled study presenting MRI-based and clinical outcomes after 5 years.
      ,
      • Akgun I.
      • Unlu M.C.
      • Erdal O.A.
      • et al.
      Matrix-induced autologous mesenchymal stem cell implantation versus matrix-induced autologous chondrocyte implantation in the treatment of chondral defects of the knee: A 2-year randomized study.
      • Barié A.
      • Kruck P.
      • Sorbi R.
      • et al.
      Prospective long-term follow-up of autologous chondrocyte implantation with periosteum versus matrix-associated autologous chondrocyte implantation: A randomized clinical trial.
      • Basad E.
      • Ishaque B.
      • Bachmann G.
      • Stürz H.
      • Steinmeyer J.
      Matrix-induced autologous chondrocyte implantation versus microfracture in the treatment of cartilage defects of the knee: A 2-year randomised study.
      • Clavé A.
      • Potel J.F.
      • Servien E.
      • et al.
      Third-generation autologous chondrocyte implantation versus mosaicplasty for knee cartilage injury: 2-year randomized trial.
      • 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.
      • Ebert J.R.
      • Fallon M.
      • Ackland T.R.
      • Janes G.C.
      • Wood D.J.
      Minimum 10-year clinical and radiological outcomes of a randomized controlled trial evaluating 2 different approaches to full weightbearing after matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Fallon M.
      • Robertson W.B.
      • et al.
      Radiological assessment of accelerated versus traditional approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Fallon M.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.R.
      A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: Findings at 5 years.
      • Ebert J.R.
      • Lloyd D.G.
      • Ackland T.
      • Wood D.J.
      Knee biomechanics during walking gait following matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      A prospective, randomized comparison of traditional and accelerated approaches to postoperative rehabilitation following autologous chondrocyte implantation: 2-year clinical outcomes.
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      Traditional vs accelerated approaches to post-operative rehabilitation following matrix-induced autologous chondrocyte implantation (MACI): Comparison of clinical, biomechanical and radiographic outcomes.
      • Edwards P.K.
      • Ackland T.R.
      • Ebert J.R.
      Accelerated weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint: Early clinical and radiological outcomes.
      • Fossum V.
      • Hansen A.K.
      • Wilsgaard T.
      • Knutsen G.
      Collagen-covered autologous chondrocyte implantation versus autologous matrix-induced chondrogenesis: A randomized trial comparing 2 methods for repair of cartilage defects of the knee.
      • Hoburg A.
      • Niemeyer P.
      • Laute V.
      • et al.
      Matrix-associated autologous chondrocyte implantation with spheroid technology is superior to arthroscopic microfracture at 36 months regarding activities of daily living and sporting activities after treatment.
      • Ibarra C.
      • Villalobos E.
      • Madrazo-Ibarra A.
      • et al.
      Arthoscopic matrix-assisted autologous chondrocyte transplantation versus microfracture: A 6-year follow-up of a prospective randomized trial.
      • Liu Y.L.
      • Yen C.C.
      • Liu T.T.
      • et al.
      Safety and efficacy of Kartigen® in treating cartilage defects: A randomized, controlled, phase I trial.
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      Safety and efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology is independent of spheroid dose after 4 years.
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      A prospective, randomized, open-label, multicenter, Phase III noninferiority trial to compare the clinical efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology versus arthroscopic microfracture for cartilage defects of the knee.
      • Zeifang F.
      • Oberle D.
      • Nierhoff C.
      • et al.
      Autologous chondrocyte implantation using the original periosteum-cover technique versus matrix-associated autologous chondrocyte implantation: A randomized clinical trial.
      reported on postoperative WB (Table 2). All but 2 studies
      • Basad E.
      • Ishaque B.
      • Bachmann G.
      • Stürz H.
      • Steinmeyer J.
      Matrix-induced autologous chondrocyte implantation versus microfracture in the treatment of cartilage defects of the knee: A 2-year randomised study.
      ,
      • Clavé A.
      • Potel J.F.
      • Servien E.
      • et al.
      Third-generation autologous chondrocyte implantation versus mosaicplasty for knee cartilage injury: 2-year randomized trial.
      allowed partial WB immediately after operation. One study
      • Liu Y.L.
      • Yen C.C.
      • Liu T.T.
      • et al.
      Safety and efficacy of Kartigen® in treating cartilage defects: A randomized, controlled, phase I trial.
      allowed full WB at 4 weeks, 9 studies
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      ,
      • Wondrasch B.
      • Risberg M.A.
      • Zak L.
      • Marlovits S.
      • Aldrian S.
      Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle: a prospective, randomized controlled study presenting MRI-based and clinical outcomes after 5 years.
      ,
      • Barié A.
      • Kruck P.
      • Sorbi R.
      • et al.
      Prospective long-term follow-up of autologous chondrocyte implantation with periosteum versus matrix-associated autologous chondrocyte implantation: A randomized clinical trial.
      ,
      • 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.
      ,
      • Edwards P.K.
      • Ackland T.R.
      • Ebert J.R.
      Accelerated weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint: Early clinical and radiological outcomes.
      ,
      • Fossum V.
      • Hansen A.K.
      • Wilsgaard T.
      • Knutsen G.
      Collagen-covered autologous chondrocyte implantation versus autologous matrix-induced chondrogenesis: A randomized trial comparing 2 methods for repair of cartilage defects of the knee.
      ,
      • Ibarra C.
      • Villalobos E.
      • Madrazo-Ibarra A.
      • et al.
      Arthoscopic matrix-assisted autologous chondrocyte transplantation versus microfracture: A 6-year follow-up of a prospective randomized trial.
      ,
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      Safety and efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology is independent of spheroid dose after 4 years.
      ,
      • Zeifang F.
      • Oberle D.
      • Nierhoff C.
      • et al.
      Autologous chondrocyte implantation using the original periosteum-cover technique versus matrix-associated autologous chondrocyte implantation: A randomized clinical trial.
      allowed full WB at 6 weeks, 11 studies
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      ,
      • Basad E.
      • Ishaque B.
      • Bachmann G.
      • Stürz H.
      • Steinmeyer J.
      Matrix-induced autologous chondrocyte implantation versus microfracture in the treatment of cartilage defects of the knee: A 2-year randomised study.
      ,
      • Ebert J.R.
      • Fallon M.
      • Ackland T.R.
      • Janes G.C.
      • Wood D.J.
      Minimum 10-year clinical and radiological outcomes of a randomized controlled trial evaluating 2 different approaches to full weightbearing after matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Fallon M.
      • Robertson W.B.
      • et al.
      Radiological assessment of accelerated versus traditional approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Fallon M.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.R.
      A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: Findings at 5 years.
      • Ebert J.R.
      • Lloyd D.G.
      • Ackland T.
      • Wood D.J.
      Knee biomechanics during walking gait following matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      A prospective, randomized comparison of traditional and accelerated approaches to postoperative rehabilitation following autologous chondrocyte implantation: 2-year clinical outcomes.
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      Traditional vs accelerated approaches to post-operative rehabilitation following matrix-induced autologous chondrocyte implantation (MACI): Comparison of clinical, biomechanical and radiographic outcomes.
      • Edwards P.K.
      • Ackland T.R.
      • Ebert J.R.
      Accelerated weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint: Early clinical and radiological outcomes.
      ,
      • Hoburg A.
      • Niemeyer P.
      • Laute V.
      • et al.
      Matrix-associated autologous chondrocyte implantation with spheroid technology is superior to arthroscopic microfracture at 36 months regarding activities of daily living and sporting activities after treatment.
      ,
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      A prospective, randomized, open-label, multicenter, Phase III noninferiority trial to compare the clinical efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology versus arthroscopic microfracture for cartilage defects of the knee.
      allowed full WB at 8 weeks, and 10 studies
      • Brittberg M.
      • Recker D.
      • Ilgenfritz J.
      • Saris D.B.F.
      SUMMIT Extension Study Group. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: Five-year follow-up of a prospective randomized trial.
      ,
      • Wondrasch B.
      • Risberg M.A.
      • Zak L.
      • Marlovits S.
      • Aldrian S.
      Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle: a prospective, randomized controlled study presenting MRI-based and clinical outcomes after 5 years.
      ,
      • Akgun I.
      • Unlu M.C.
      • Erdal O.A.
      • et al.
      Matrix-induced autologous mesenchymal stem cell implantation versus matrix-induced autologous chondrocyte implantation in the treatment of chondral defects of the knee: A 2-year randomized study.
      ,
      • Clavé A.
      • Potel J.F.
      • Servien E.
      • et al.
      Third-generation autologous chondrocyte implantation versus mosaicplasty for knee cartilage injury: 2-year randomized trial.
      ,
      • Ebert J.R.
      • Fallon M.
      • Ackland T.R.
      • Janes G.C.
      • Wood D.J.
      Minimum 10-year clinical and radiological outcomes of a randomized controlled trial evaluating 2 different approaches to full weightbearing after matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Fallon M.
      • Robertson W.B.
      • et al.
      Radiological assessment of accelerated versus traditional approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Fallon M.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.R.
      A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: Findings at 5 years.
      • Ebert J.R.
      • Lloyd D.G.
      • Ackland T.
      • Wood D.J.
      Knee biomechanics during walking gait following matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      A prospective, randomized comparison of traditional and accelerated approaches to postoperative rehabilitation following autologous chondrocyte implantation: 2-year clinical outcomes.
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      Traditional vs accelerated approaches to post-operative rehabilitation following matrix-induced autologous chondrocyte implantation (MACI): Comparison of clinical, biomechanical and radiographic outcomes.
      allowed full WB at 10 to 12 weeks’ postoperatively. Three studies
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      ,
      • Edwards P.K.
      • Ackland T.R.
      • Ebert J.R.
      Accelerated weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint: Early clinical and radiological outcomes.
      ,
      • Wondrasch B.
      • Risberg M.A.
      • Zak L.
      • Marlovits S.
      • Aldrian S.
      Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle: a prospective, randomized controlled study presenting MRI-based and clinical outcomes after 5 years.
      consisted of an initial 2-week period of WB at 20%, followed by a progressive increase to full WB at 6 weeks’ postoperatively. Eight studies
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      ,
      • Ebert J.R.
      • Fallon M.
      • Ackland T.R.
      • Janes G.C.
      • Wood D.J.
      Minimum 10-year clinical and radiological outcomes of a randomized controlled trial evaluating 2 different approaches to full weightbearing after matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Fallon M.
      • Robertson W.B.
      • et al.
      Radiological assessment of accelerated versus traditional approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Fallon M.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.R.
      A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: Findings at 5 years.
      • Ebert J.R.
      • Lloyd D.G.
      • Ackland T.
      • Wood D.J.
      Knee biomechanics during walking gait following matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      A prospective, randomized comparison of traditional and accelerated approaches to postoperative rehabilitation following autologous chondrocyte implantation: 2-year clinical outcomes.
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      Traditional vs accelerated approaches to post-operative rehabilitation following matrix-induced autologous chondrocyte implantation (MACI): Comparison of clinical, biomechanical and radiographic outcomes.
      • Edwards P.K.
      • Ackland T.R.
      • Ebert J.R.
      Accelerated weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint: Early clinical and radiological outcomes.
      consisted of a 2-week period of WB at 20%, with a progressive increase to full WB at 8 weeks’ postoperatively. One study
      • Wondrasch B.
      • Risberg M.A.
      • Zak L.
      • Marlovits S.
      • Aldrian S.
      Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle: a prospective, randomized controlled study presenting MRI-based and clinical outcomes after 5 years.
      described a 10-week rehabilitation protocol consisting of toe-touch WB for 4 weeks, followed by partial WB at 20% between weeks 4 and 6, 50% WB between weeks 6 and 8, and full WB by 10 weeks’ postoperatively. Five studies
      • Ebert J.R.
      • Fallon M.
      • Robertson W.B.
      • et al.
      Radiological assessment of accelerated versus traditional approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Fallon M.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.R.
      A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: Findings at 5 years.
      • Ebert J.R.
      • Lloyd D.G.
      • Ackland T.
      • Wood D.J.
      Knee biomechanics during walking gait following matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      A prospective, randomized comparison of traditional and accelerated approaches to postoperative rehabilitation following autologous chondrocyte implantation: 2-year clinical outcomes.
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      Traditional vs accelerated approaches to post-operative rehabilitation following matrix-induced autologous chondrocyte implantation (MACI): Comparison of clinical, biomechanical and radiographic outcomes.
      consisted of a 5-week period of WB at 20% with a progressive increase to full WB at 11 weeks’ postoperatively. One study
      • Ebert J.R.
      • Fallon M.
      • Ackland T.R.
      • Janes G.C.
      • Wood D.J.
      Minimum 10-year clinical and radiological outcomes of a randomized controlled trial evaluating 2 different approaches to full weightbearing after matrix-induced autologous chondrocyte implantation.
      consisted of a 2-week period of WB at 20%, with a progressive increase to full WB at 12 weeks’ postoperatively.
      Table 2Postoperative WB
      StudyInitial WB StatusProgression to Full WB
      Akgun et al., 2015
      • Akgun I.
      • Unlu M.C.
      • Erdal O.A.
      • et al.
      Matrix-induced autologous mesenchymal stem cell implantation versus matrix-induced autologous chondrocyte implantation in the treatment of chondral defects of the knee: A 2-year randomized study.
      Partial WB12 weeks
      Barié et al., 2020
      • Barié A.
      • Kruck P.
      • Sorbi R.
      • et al.
      Prospective long-term follow-up of autologous chondrocyte implantation with periosteum versus matrix-associated autologous chondrocyte implantation: A randomized clinical trial.
      Partial WB6 weeks
      Basad et al., 2010
      • Basad E.
      • Ishaque B.
      • Bachmann G.
      • Stürz H.
      • Steinmeyer J.
      Matrix-induced autologous chondrocyte implantation versus microfracture in the treatment of cartilage defects of the knee: A 2-year randomised study.
      Non-WB8 weeks
      Brittberg et al., 2018
      • Brittberg M.
      • Recker D.
      • Ilgenfritz J.
      • Saris D.B.F.
      SUMMIT Extension Study Group. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: Five-year follow-up of a prospective randomized trial.
      Partial WB12 weeks
      Clavé et al., 2016
      • Clavé A.
      • Potel J.F.
      • Servien E.
      • et al.
      Third-generation autologous chondrocyte implantation versus mosaicplasty for knee cartilage injury: 2-year randomized trial.
      Non-WB10 weeks
      Crawford et al., 2012
      • 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.
      Partial WB6 weeks
      Ebert et al., 2020
      • Ebert J.R.
      • Fallon M.
      • Ackland T.R.
      • Janes G.C.
      • Wood D.J.
      Minimum 10-year clinical and radiological outcomes of a randomized controlled trial evaluating 2 different approaches to full weightbearing after matrix-induced autologous chondrocyte implantation.
      Partial WB8 weeks/12 weeks
      These studies compared return to full WB at 2 different time points.
      Ebert et al., 2011
      • Ebert J.R.
      • Fallon M.
      • Robertson W.B.
      • et al.
      Radiological assessment of accelerated versus traditional approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation.
      Partial WB8 weeks/11 weeks
      These studies compared return to full WB at 2 different time points.
      Ebert et al., 2021
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      Partial WB6 weeks/8 weeks
      These studies compared return to full WB at 2 different time points.
      Ebert et al., 2012
      • Ebert J.R.
      • Fallon M.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.R.
      A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: Findings at 5 years.
      Partial WB8 weeks/11 weeks
      These studies compared return to full WB at 2 different time points.
      Ebert et al., 2010
      • Ebert J.R.
      • Lloyd D.G.
      • Ackland T.
      • Wood D.J.
      Knee biomechanics during walking gait following matrix-induced autologous chondrocyte implantation.
      Partial WB8 weeks/11 weeks
      These studies compared return to full WB at 2 different time points.
      Ebert et al., 2010
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      A prospective, randomized comparison of traditional and accelerated approaches to postoperative rehabilitation following autologous chondrocyte implantation: 2-year clinical outcomes.
      Partial WB8 weeks/11 weeks
      These studies compared return to full WB at 2 different time points.
      Ebert et al., 2008
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      Traditional vs accelerated approaches to post-operative rehabilitation following matrix-induced autologous chondrocyte implantation (MACI): Comparison of clinical, biomechanical and radiographic outcomes.
      Partial WB8 weeks/11 weeks
      These studies compared return to full WB at 2 different time points.
      Edwards et al., 2013
      • Edwards P.K.
      • Ackland T.R.
      • Ebert J.R.
      Accelerated weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint: Early clinical and radiological outcomes.
      Partial WB6 weeks/8 weeks
      These studies compared return to full WB at 2 different time points.
      Fossum et al., 2019
      • Fossum V.
      • Hansen A.K.
      • Wilsgaard T.
      • Knutsen G.
      Collagen-covered autologous chondrocyte implantation versus autologous matrix-induced chondrogenesis: A randomized trial comparing 2 methods for repair of cartilage defects of the knee.
      Partial WB6 weeks
      Hoburg et al., 2021
      • Hoburg A.
      • Niemeyer P.
      • Laute V.
      • et al.
      Matrix-associated autologous chondrocyte implantation with spheroid technology is superior to arthroscopic microfracture at 36 months regarding activities of daily living and sporting activities after treatment.
      Partial WB8 weeks
      Ibarra et al., 2021
      • Ibarra C.
      • Villalobos E.
      • Madrazo-Ibarra A.
      • et al.
      Arthoscopic matrix-assisted autologous chondrocyte transplantation versus microfracture: A 6-year follow-up of a prospective randomized trial.
      Partial WB6 weeks
      Liu et al., 2021
      • Liu Y.L.
      • Yen C.C.
      • Liu T.T.
      • et al.
      Safety and efficacy of Kartigen® in treating cartilage defects: A randomized, controlled, phase I trial.
      Partial WB4 weeks
      Niemeyer et al., 2020
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      Safety and efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology is independent of spheroid dose after 4 years.
      Partial WB6 weeks
      Niemeyer et al., 2019
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      A prospective, randomized, open-label, multicenter, Phase III noninferiority trial to compare the clinical efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology versus arthroscopic microfracture for cartilage defects of the knee.
      Partial WB8 weeks
      Wondrasch et al., 2015
      • Wondrasch B.
      • Risberg M.A.
      • Zak L.
      • Marlovits S.
      • Aldrian S.
      Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle: a prospective, randomized controlled study presenting MRI-based and clinical outcomes after 5 years.
      Partial WB6 weeks/10 weeks
      These studies compared return to full WB at 2 different time points.
      Zeifang et al., 2010
      • Zeifang F.
      • Oberle D.
      • Nierhoff C.
      • et al.
      Autologous chondrocyte implantation using the original periosteum-cover technique versus matrix-associated autologous chondrocyte implantation: A randomized clinical trial.
      Partial WB6 weeks
      WB, weight-bearing.
      These studies compared return to full WB at 2 different time points.

      Continuous Passive Motion

      Eighteen studies
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      ,
      • Wondrasch B.
      • Risberg M.A.
      • Zak L.
      • Marlovits S.
      • Aldrian S.
      Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle: a prospective, randomized controlled study presenting MRI-based and clinical outcomes after 5 years.
      ,
      • Akgun I.
      • Unlu M.C.
      • Erdal O.A.
      • et al.
      Matrix-induced autologous mesenchymal stem cell implantation versus matrix-induced autologous chondrocyte implantation in the treatment of chondral defects of the knee: A 2-year randomized study.
      • Barié A.
      • Kruck P.
      • Sorbi R.
      • et al.
      Prospective long-term follow-up of autologous chondrocyte implantation with periosteum versus matrix-associated autologous chondrocyte implantation: A randomized clinical trial.
      • Basad E.
      • Ishaque B.
      • Bachmann G.
      • Stürz H.
      • Steinmeyer J.
      Matrix-induced autologous chondrocyte implantation versus microfracture in the treatment of cartilage defects of the knee: A 2-year randomised study.
      ,
      • 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.
      • Ebert J.R.
      • Fallon M.
      • Ackland T.R.
      • Janes G.C.
      • Wood D.J.
      Minimum 10-year clinical and radiological outcomes of a randomized controlled trial evaluating 2 different approaches to full weightbearing after matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Fallon M.
      • Robertson W.B.
      • et al.
      Radiological assessment of accelerated versus traditional approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Fallon M.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.R.
      A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: Findings at 5 years.
      ,
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      A prospective, randomized comparison of traditional and accelerated approaches to postoperative rehabilitation following autologous chondrocyte implantation: 2-year clinical outcomes.
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      Traditional vs accelerated approaches to post-operative rehabilitation following matrix-induced autologous chondrocyte implantation (MACI): Comparison of clinical, biomechanical and radiographic outcomes.
      • Edwards P.K.
      • Ackland T.R.
      • Ebert J.R.
      Accelerated weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint: Early clinical and radiological outcomes.
      • Fossum V.
      • Hansen A.K.
      • Wilsgaard T.
      • Knutsen G.
      Collagen-covered autologous chondrocyte implantation versus autologous matrix-induced chondrogenesis: A randomized trial comparing 2 methods for repair of cartilage defects of the knee.
      • Hoburg A.
      • Niemeyer P.
      • Laute V.
      • et al.
      Matrix-associated autologous chondrocyte implantation with spheroid technology is superior to arthroscopic microfracture at 36 months regarding activities of daily living and sporting activities after treatment.
      • Ibarra C.
      • Villalobos E.
      • Madrazo-Ibarra A.
      • et al.
      Arthoscopic matrix-assisted autologous chondrocyte transplantation versus microfracture: A 6-year follow-up of a prospective randomized trial.
      ,
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      Safety and efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology is independent of spheroid dose after 4 years.
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      A prospective, randomized, open-label, multicenter, Phase III noninferiority trial to compare the clinical efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology versus arthroscopic microfracture for cartilage defects of the knee.
      • Zeifang F.
      • Oberle D.
      • Nierhoff C.
      • et al.
      Autologous chondrocyte implantation using the original periosteum-cover technique versus matrix-associated autologous chondrocyte implantation: A randomized clinical trial.
      used CPM as part of the rehabilitation process for all patients included (Table 3). In most studies, CPM was initiated within 12 to 24 hours of surgery with an initial range of motion (ROM) of 0 to 30° of knee flexion.
      Table 3Continuous Passive Motion (CPM)
      StudyInitiation of CPM (Postoperatively)Initial ROMDuration of CPM
      Akgun et al., 2015
      • Akgun I.
      • Unlu M.C.
      • Erdal O.A.
      • et al.
      Matrix-induced autologous mesenchymal stem cell implantation versus matrix-induced autologous chondrocyte implantation in the treatment of chondral defects of the knee: A 2-year randomized study.
      12-24 hours0°-30°1 hour/NR
      Barié et al., 2020
      • Barié A.
      • Kruck P.
      • Sorbi R.
      • et al.
      Prospective long-term follow-up of autologous chondrocyte implantation with periosteum versus matrix-associated autologous chondrocyte implantation: A randomized clinical trial.
      24 hoursNRNR/6 weeks
      Basad et al., 2010
      • Basad E.
      • Ishaque B.
      • Bachmann G.
      • Stürz H.
      • Steinmeyer J.
      Matrix-induced autologous chondrocyte implantation versus microfracture in the treatment of cartilage defects of the knee: A 2-year randomised study.
      NRNRNR
      Crawford et al., 2012
      • 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.
      24 hoursNRNR
      Ebert et al., 2020
      • Ebert J.R.
      • Fallon M.
      • Ackland T.R.
      • Janes G.C.
      • Wood D.J.
      Minimum 10-year clinical and radiological outcomes of a randomized controlled trial evaluating 2 different approaches to full weightbearing after matrix-induced autologous chondrocyte implantation.
      NR0°–30°NR
      Ebert et al., 2011
      • Ebert J.R.
      • Fallon M.
      • Robertson W.B.
      • et al.
      Radiological assessment of accelerated versus traditional approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation.
      NR0°–30°NR/3 weeks
      Ebert et al., 2021
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      12-24 hours0°–30°1 hour/NR
      Ebert et al., 2012
      • Ebert J.R.
      • Fallon M.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.R.
      A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: Findings at 5 years.
      12-24 hours0°–30°NR
      Ebert et al., 2010
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      A prospective, randomized comparison of traditional and accelerated approaches to postoperative rehabilitation following autologous chondrocyte implantation: 2-year clinical outcomes.
      12-24 hours0°–30°NR
      Ebert et al., 2008
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      Traditional vs accelerated approaches to post-operative rehabilitation following matrix-induced autologous chondrocyte implantation (MACI): Comparison of clinical, biomechanical and radiographic outcomes.
      12-24 hours0°–30°1 hour/NR
      Edwards et al., 2013
      • Edwards P.K.
      • Ackland T.R.
      • Ebert J.R.
      Accelerated weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint: Early clinical and radiological outcomes.
      12-24 hours0°–30°1 hour/NR
      Fossum et al., 2019
      • Fossum V.
      • Hansen A.K.
      • Wilsgaard T.
      • Knutsen G.
      Collagen-covered autologous chondrocyte implantation versus autologous matrix-induced chondrogenesis: A randomized trial comparing 2 methods for repair of cartilage defects of the knee.
      NRNR4 hours/5 days
      Hoburg et al., 2021
      • Hoburg A.
      • Niemeyer P.
      • Laute V.
      • et al.
      Matrix-associated autologous chondrocyte implantation with spheroid technology is superior to arthroscopic microfracture at 36 months regarding activities of daily living and sporting activities after treatment.
      24 hours0°–60°NR/6 weeks
      Ibarra et al., 2021
      • Ibarra C.
      • Villalobos E.
      • Madrazo-Ibarra A.
      • et al.
      Arthoscopic matrix-assisted autologous chondrocyte transplantation versus microfracture: A 6-year follow-up of a prospective randomized trial.
      72 hours0°–40°4 hours/NR
      Niemeyer et al., 2020
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      Safety and efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology is independent of spheroid dose after 4 years.
      24 hours0°–60°NR/6 weeks
      Niemeyer et al., 2019
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      A prospective, randomized, open-label, multicenter, Phase III noninferiority trial to compare the clinical efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology versus arthroscopic microfracture for cartilage defects of the knee.
      24 hours0°–60°NR/6 weeks
      Wondrasch et al., 2015
      • Wondrasch B.
      • Risberg M.A.
      • Zak L.
      • Marlovits S.
      • Aldrian S.
      Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle: a prospective, randomized controlled study presenting MRI-based and clinical outcomes after 5 years.
      48 hours0°–40°3 hours/NR
      Zeifang et al., 2010
      • Zeifang F.
      • Oberle D.
      • Nierhoff C.
      • et al.
      Autologous chondrocyte implantation using the original periosteum-cover technique versus matrix-associated autologous chondrocyte implantation: A randomized clinical trial.
      24 hoursNRNR/6 weeks
      NOTE. Duration of CPM values are reported as hours per day/total number of days or weeks that CPM was used.
      NR, not reported; ROM, range of motion.

      Return-to-Play

      Ten studies
      • Brittberg M.
      • Recker D.
      • Ilgenfritz J.
      • Saris D.B.F.
      SUMMIT Extension Study Group. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: Five-year follow-up of a prospective randomized trial.
      ,
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      ,
      • Barié A.
      • Kruck P.
      • Sorbi R.
      • et al.
      Prospective long-term follow-up of autologous chondrocyte implantation with periosteum versus matrix-associated autologous chondrocyte implantation: A randomized clinical trial.
      ,
      • 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.
      ,
      • Ebert J.R.
      • Fallon M.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.R.
      A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: Findings at 5 years.
      ,
      • Hoburg A.
      • Niemeyer P.
      • Laute V.
      • et al.
      Matrix-associated autologous chondrocyte implantation with spheroid technology is superior to arthroscopic microfracture at 36 months regarding activities of daily living and sporting activities after treatment.
      ,
      • Ibarra C.
      • Villalobos E.
      • Madrazo-Ibarra A.
      • et al.
      Arthoscopic matrix-assisted autologous chondrocyte transplantation versus microfracture: A 6-year follow-up of a prospective randomized trial.
      ,
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      Safety and efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology is independent of spheroid dose after 4 years.
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      A prospective, randomized, open-label, multicenter, Phase III noninferiority trial to compare the clinical efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology versus arthroscopic microfracture for cartilage defects of the knee.
      • Zeifang F.
      • Oberle D.
      • Nierhoff C.
      • et al.
      Autologous chondrocyte implantation using the original periosteum-cover technique versus matrix-associated autologous chondrocyte implantation: A randomized clinical trial.
      reported on the time to RTP following surgery. In 9 studies,
      • Brittberg M.
      • Recker D.
      • Ilgenfritz J.
      • Saris D.B.F.
      SUMMIT Extension Study Group. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: Five-year follow-up of a prospective randomized trial.
      ,
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      ,
      • Barié A.
      • Kruck P.
      • Sorbi R.
      • et al.
      Prospective long-term follow-up of autologous chondrocyte implantation with periosteum versus matrix-associated autologous chondrocyte implantation: A randomized clinical trial.
      ,
      • Ebert J.R.
      • Fallon M.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.R.
      A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: Findings at 5 years.
      ,
      • Hoburg A.
      • Niemeyer P.
      • Laute V.
      • et al.
      Matrix-associated autologous chondrocyte implantation with spheroid technology is superior to arthroscopic microfracture at 36 months regarding activities of daily living and sporting activities after treatment.
      ,
      • Ibarra C.
      • Villalobos E.
      • Madrazo-Ibarra A.
      • et al.
      Arthoscopic matrix-assisted autologous chondrocyte transplantation versus microfracture: A 6-year follow-up of a prospective randomized trial.
      ,
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      Safety and efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology is independent of spheroid dose after 4 years.
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      A prospective, randomized, open-label, multicenter, Phase III noninferiority trial to compare the clinical efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology versus arthroscopic microfracture for cartilage defects of the knee.
      • Zeifang F.
      • Oberle D.
      • Nierhoff C.
      • et al.
      Autologous chondrocyte implantation using the original periosteum-cover technique versus matrix-associated autologous chondrocyte implantation: A randomized clinical trial.
      RTP was allowed at 12 months after ACI. In one study,
      • 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.
      sports activity was allowed after 6 months.

      Physical Therapy

      Thirteen studies
      • Brittberg M.
      • Recker D.
      • Ilgenfritz J.
      • Saris D.B.F.
      SUMMIT Extension Study Group. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: Five-year follow-up of a prospective randomized trial.
      ,
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      ,
      • Wondrasch B.
      • Risberg M.A.
      • Zak L.
      • Marlovits S.
      • Aldrian S.
      Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle: a prospective, randomized controlled study presenting MRI-based and clinical outcomes after 5 years.
      ,
      • Ebert J.R.
      • Fallon M.
      • Ackland T.R.
      • Janes G.C.
      • Wood D.J.
      Minimum 10-year clinical and radiological outcomes of a randomized controlled trial evaluating 2 different approaches to full weightbearing after matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Fallon M.
      • Robertson W.B.
      • et al.
      Radiological assessment of accelerated versus traditional approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Fallon M.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.R.
      A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: Findings at 5 years.
      ,
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      A prospective, randomized comparison of traditional and accelerated approaches to postoperative rehabilitation following autologous chondrocyte implantation: 2-year clinical outcomes.
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      Traditional vs accelerated approaches to post-operative rehabilitation following matrix-induced autologous chondrocyte implantation (MACI): Comparison of clinical, biomechanical and radiographic outcomes.
      • Edwards P.K.
      • Ackland T.R.
      • Ebert J.R.
      Accelerated weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint: Early clinical and radiological outcomes.
      ,
      • Hoburg A.
      • Niemeyer P.
      • Laute V.
      • et al.
      Matrix-associated autologous chondrocyte implantation with spheroid technology is superior to arthroscopic microfracture at 36 months regarding activities of daily living and sporting activities after treatment.
      ,
      • Ibarra C.
      • Villalobos E.
      • Madrazo-Ibarra A.
      • et al.
      Arthoscopic matrix-assisted autologous chondrocyte transplantation versus microfracture: A 6-year follow-up of a prospective randomized trial.
      ,
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      Safety and efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology is independent of spheroid dose after 4 years.
      ,
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      A prospective, randomized, open-label, multicenter, Phase III noninferiority trial to compare the clinical efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology versus arthroscopic microfracture for cartilage defects of the knee.
      used isometric exercises as part of their postoperative rehabilitation protocol (Table 4). Ten studies
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      ,
      • Clavé A.
      • Potel J.F.
      • Servien E.
      • et al.
      Third-generation autologous chondrocyte implantation versus mosaicplasty for knee cartilage injury: 2-year randomized trial.
      ,
      • Ebert J.R.
      • Fallon M.
      • Robertson W.B.
      • et al.
      Radiological assessment of accelerated versus traditional approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Fallon M.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.R.
      A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: Findings at 5 years.
      • Ebert J.R.
      • Lloyd D.G.
      • Ackland T.
      • Wood D.J.
      Knee biomechanics during walking gait following matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      A prospective, randomized comparison of traditional and accelerated approaches to postoperative rehabilitation following autologous chondrocyte implantation: 2-year clinical outcomes.
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      Traditional vs accelerated approaches to post-operative rehabilitation following matrix-induced autologous chondrocyte implantation (MACI): Comparison of clinical, biomechanical and radiographic outcomes.
      • Edwards P.K.
      • Ackland T.R.
      • Ebert J.R.
      Accelerated weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint: Early clinical and radiological outcomes.
      • Fossum V.
      • Hansen A.K.
      • Wilsgaard T.
      • Knutsen G.
      Collagen-covered autologous chondrocyte implantation versus autologous matrix-induced chondrogenesis: A randomized trial comparing 2 methods for repair of cartilage defects of the knee.
      ,
      • Ibarra C.
      • Villalobos E.
      • Madrazo-Ibarra A.
      • et al.
      Arthoscopic matrix-assisted autologous chondrocyte transplantation versus microfracture: A 6-year follow-up of a prospective randomized trial.
      described the use of a brace during rehabilitation. Thirteen studies
      • Brittberg M.
      • Recker D.
      • Ilgenfritz J.
      • Saris D.B.F.
      SUMMIT Extension Study Group. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: Five-year follow-up of a prospective randomized trial.
      ,
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      ,
      • Wondrasch B.
      • Risberg M.A.
      • Zak L.
      • Marlovits S.
      • Aldrian S.
      Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle: a prospective, randomized controlled study presenting MRI-based and clinical outcomes after 5 years.
      ,
      • Clavé A.
      • Potel J.F.
      • Servien E.
      • et al.
      Third-generation autologous chondrocyte implantation versus mosaicplasty for knee cartilage injury: 2-year randomized trial.
      ,
      • Ebert J.R.
      • Fallon M.
      • Robertson W.B.
      • et al.
      Radiological assessment of accelerated versus traditional approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation.
      ,
      • Ebert J.R.
      • Fallon M.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.R.
      A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: Findings at 5 years.
      ,
      • Edwards P.K.
      • Ackland T.R.
      • Ebert J.R.
      Accelerated weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint: Early clinical and radiological outcomes.
      • Fossum V.
      • Hansen A.K.
      • Wilsgaard T.
      • Knutsen G.
      Collagen-covered autologous chondrocyte implantation versus autologous matrix-induced chondrogenesis: A randomized trial comparing 2 methods for repair of cartilage defects of the knee.
      • Hoburg A.
      • Niemeyer P.
      • Laute V.
      • et al.
      Matrix-associated autologous chondrocyte implantation with spheroid technology is superior to arthroscopic microfracture at 36 months regarding activities of daily living and sporting activities after treatment.
      • Ibarra C.
      • Villalobos E.
      • Madrazo-Ibarra A.
      • et al.
      Arthoscopic matrix-assisted autologous chondrocyte transplantation versus microfracture: A 6-year follow-up of a prospective randomized trial.
      • Liu Y.L.
      • Yen C.C.
      • Liu T.T.
      • et al.
      Safety and efficacy of Kartigen® in treating cartilage defects: A randomized, controlled, phase I trial.
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      Safety and efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology is independent of spheroid dose after 4 years.
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      A prospective, randomized, open-label, multicenter, Phase III noninferiority trial to compare the clinical efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology versus arthroscopic microfracture for cartilage defects of the knee.
      stated time to full knee ROM. Three studies
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      ,
      • Ebert J.R.
      • Fallon M.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.R.
      A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: Findings at 5 years.
      ,
      • Ibarra C.
      • Villalobos E.
      • Madrazo-Ibarra A.
      • et al.
      Arthoscopic matrix-assisted autologous chondrocyte transplantation versus microfracture: A 6-year follow-up of a prospective randomized trial.
      described the use of open-chain exercises. Four studies
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      ,
      • Ebert J.R.
      • Fallon M.
      • Robertson W.B.
      • et al.
      Radiological assessment of accelerated versus traditional approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation.
      ,
      • Ebert J.R.
      • Fallon M.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.R.
      A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: Findings at 5 years.
      ,
      • Edwards P.K.
      • Ackland T.R.
      • Ebert J.R.
      Accelerated weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint: Early clinical and radiological outcomes.
      described the use of closed-chain exercises, with all 4 studies initiating these exercises at 7 weeks postoperatively. Thirteen studies
      • Brittberg M.
      • Recker D.
      • Ilgenfritz J.
      • Saris D.B.F.
      SUMMIT Extension Study Group. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: Five-year follow-up of a prospective randomized trial.
      ,
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      ,
      • Wondrasch B.
      • Risberg M.A.
      • Zak L.
      • Marlovits S.
      • Aldrian S.
      Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle: a prospective, randomized controlled study presenting MRI-based and clinical outcomes after 5 years.
      ,
      • Ebert J.R.
      • Fallon M.
      • Ackland T.R.
      • Janes G.C.
      • Wood D.J.
      Minimum 10-year clinical and radiological outcomes of a randomized controlled trial evaluating 2 different approaches to full weightbearing after matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Fallon M.
      • Robertson W.B.
      • et al.
      Radiological assessment of accelerated versus traditional approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Fallon M.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.R.
      A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: Findings at 5 years.
      ,
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      A prospective, randomized comparison of traditional and accelerated approaches to postoperative rehabilitation following autologous chondrocyte implantation: 2-year clinical outcomes.
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      Traditional vs accelerated approaches to post-operative rehabilitation following matrix-induced autologous chondrocyte implantation (MACI): Comparison of clinical, biomechanical and radiographic outcomes.
      • Edwards P.K.
      • Ackland T.R.
      • Ebert J.R.
      Accelerated weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint: Early clinical and radiological outcomes.
      • Fossum V.
      • Hansen A.K.
      • Wilsgaard T.
      • Knutsen G.
      Collagen-covered autologous chondrocyte implantation versus autologous matrix-induced chondrogenesis: A randomized trial comparing 2 methods for repair of cartilage defects of the knee.
      • Hoburg A.
      • Niemeyer P.
      • Laute V.
      • et al.
      Matrix-associated autologous chondrocyte implantation with spheroid technology is superior to arthroscopic microfracture at 36 months regarding activities of daily living and sporting activities after treatment.
      ,
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      Safety and efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology is independent of spheroid dose after 4 years.
      ,
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      A prospective, randomized, open-label, multicenter, Phase III noninferiority trial to compare the clinical efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology versus arthroscopic microfracture for cartilage defects of the knee.
      described the use of progressive strengthening in their rehabilitation protocol. Eight studies
      • Brittberg M.
      • Recker D.
      • Ilgenfritz J.
      • Saris D.B.F.
      SUMMIT Extension Study Group. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: Five-year follow-up of a prospective randomized trial.
      ,
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      ,
      • Ebert J.R.
      • Fallon M.
      • Robertson W.B.
      • et al.
      Radiological assessment of accelerated versus traditional approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation.
      ,
      • Ebert J.R.
      • Fallon M.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.R.
      A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: Findings at 5 years.
      ,
      • Edwards P.K.
      • Ackland T.R.
      • Ebert J.R.
      Accelerated weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint: Early clinical and radiological outcomes.
      ,
      • Hoburg A.
      • Niemeyer P.
      • Laute V.
      • et al.
      Matrix-associated autologous chondrocyte implantation with spheroid technology is superior to arthroscopic microfracture at 36 months regarding activities of daily living and sporting activities after treatment.
      ,
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      Safety and efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology is independent of spheroid dose after 4 years.
      ,
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      A prospective, randomized, open-label, multicenter, Phase III noninferiority trial to compare the clinical efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology versus arthroscopic microfracture for cartilage defects of the knee.
      described the use of neuromuscular (proprioceptive/balance) training. Eight studies
      • Brittberg M.
      • Recker D.
      • Ilgenfritz J.
      • Saris D.B.F.
      SUMMIT Extension Study Group. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: Five-year follow-up of a prospective randomized trial.
      ,
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      ,
      • Ebert J.R.
      • Fallon M.
      • Robertson W.B.
      • et al.
      Radiological assessment of accelerated versus traditional approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation.
      ,
      • Ebert J.R.
      • Fallon M.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.R.
      A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: Findings at 5 years.
      ,
      • Edwards P.K.
      • Ackland T.R.
      • Ebert J.R.
      Accelerated weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint: Early clinical and radiological outcomes.
      ,
      • Hoburg A.
      • Niemeyer P.
      • Laute V.
      • et al.
      Matrix-associated autologous chondrocyte implantation with spheroid technology is superior to arthroscopic microfracture at 36 months regarding activities of daily living and sporting activities after treatment.
      ,
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      Safety and efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology is independent of spheroid dose after 4 years.
      ,
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      A prospective, randomized, open-label, multicenter, Phase III noninferiority trial to compare the clinical efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology versus arthroscopic microfracture for cartilage defects of the knee.
      addressed initiation of sports-specific movements. Eight studies
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      ,
      • Akgun I.
      • Unlu M.C.
      • Erdal O.A.
      • et al.
      Matrix-induced autologous mesenchymal stem cell implantation versus matrix-induced autologous chondrocyte implantation in the treatment of chondral defects of the knee: A 2-year randomized study.
      ,
      • Ebert J.R.
      • Fallon M.
      • Ackland T.R.
      • Janes G.C.
      • Wood D.J.
      Minimum 10-year clinical and radiological outcomes of a randomized controlled trial evaluating 2 different approaches to full weightbearing after matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Fallon M.
      • Robertson W.B.
      • et al.
      Radiological assessment of accelerated versus traditional approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Fallon M.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.R.
      A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: Findings at 5 years.
      ,
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      A prospective, randomized comparison of traditional and accelerated approaches to postoperative rehabilitation following autologous chondrocyte implantation: 2-year clinical outcomes.
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      Traditional vs accelerated approaches to post-operative rehabilitation following matrix-induced autologous chondrocyte implantation (MACI): Comparison of clinical, biomechanical and radiographic outcomes.
      • Edwards P.K.
      • Ackland T.R.
      • Ebert J.R.
      Accelerated weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint: Early clinical and radiological outcomes.
      used cryotherapy to control edema.
      Table 4Rehabilitation Protocols
      StudyIsometric ExerciseBrace DurationTime to Full ROMOpen-Chain ExercisesClosed-Chain ExercisesProgressive StrengtheningNeuromuscular TrainingSports-Specific Movements
      Brittberg et al., 2018
      • Brittberg M.
      • Recker D.
      • Ilgenfritz J.
      • Saris D.B.F.
      SUMMIT Extension Study Group. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: Five-year follow-up of a prospective randomized trial.
      NR1261212
      Clavé et al., 2016
      • Clavé A.
      • Potel J.F.
      • Servien E.
      • et al.
      Third-generation autologous chondrocyte implantation versus mosaicplasty for knee cartilage injury: 2-year randomized trial.
      410
      Ebert et al., 2020
      • Ebert J.R.
      • Fallon M.
      • Ackland T.R.
      • Janes G.C.
      • Wood D.J.
      Minimum 10-year clinical and radiological outcomes of a randomized controlled trial evaluating 2 different approaches to full weightbearing after matrix-induced autologous chondrocyte implantation.
      NRNR
      Ebert et al., 2011
      • Ebert J.R.
      • Fallon M.
      • Robertson W.B.
      • et al.
      Radiological assessment of accelerated versus traditional approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation.
      11257477
      Ebert et al., 2021
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      1125127477
      Ebert et al., 2012
      • Ebert J.R.
      • Fallon M.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.R.
      A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: Findings at 5 years.
      1127127777
      Ebert et al., 2010
      • Ebert J.R.
      • Lloyd D.G.
      • Ackland T.
      • Wood D.J.
      Knee biomechanics during walking gait following matrix-induced autologous chondrocyte implantation.
      12
      Ebert et al., 2010
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      A prospective, randomized comparison of traditional and accelerated approaches to postoperative rehabilitation following autologous chondrocyte implantation: 2-year clinical outcomes.
      NR12NR
      Ebert et al., 2008
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      Traditional vs accelerated approaches to post-operative rehabilitation following matrix-induced autologous chondrocyte implantation (MACI): Comparison of clinical, biomechanical and radiographic outcomes.
      NR11NR
      Edwards et al., 2013
      • Edwards P.K.
      • Ackland T.R.
      • Ebert J.R.
      Accelerated weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint: Early clinical and radiological outcomes.
      1857477
      Fossum et al., 2019
      • Fossum V.
      • Hansen A.K.
      • Wilsgaard T.
      • Knutsen G.
      Collagen-covered autologous chondrocyte implantation versus autologous matrix-induced chondrogenesis: A randomized trial comparing 2 methods for repair of cartilage defects of the knee.
      6NRNR
      Hoburg et al., 2021
      • Hoburg A.
      • Niemeyer P.
      • Laute V.
      • et al.
      Matrix-associated autologous chondrocyte implantation with spheroid technology is superior to arthroscopic microfracture at 36 months regarding activities of daily living and sporting activities after treatment.
      NR7777
      Ibarra et al., 2021
      • Ibarra C.
      • Villalobos E.
      • Madrazo-Ibarra A.
      • et al.
      Arthoscopic matrix-assisted autologous chondrocyte transplantation versus microfracture: A 6-year follow-up of a prospective randomized trial.
      16616
      Liu et al., 2021
      • Liu Y.L.
      • Yen C.C.
      • Liu T.T.
      • et al.
      Safety and efficacy of Kartigen® in treating cartilage defects: A randomized, controlled, phase I trial.
      3 days
      Niemeyer et al., 2020
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      Safety and efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology is independent of spheroid dose after 4 years.
      17777
      Niemeyer et al., 2019
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      A prospective, randomized, open-label, multicenter, Phase III noninferiority trial to compare the clinical efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology versus arthroscopic microfracture for cartilage defects of the knee.
      17777
      Wondrasch et al., 2015
      • Wondrasch B.
      • Risberg M.A.
      • Zak L.
      • Marlovits S.
      • Aldrian S.
      Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle: a prospective, randomized controlled study presenting MRI-based and clinical outcomes after 5 years.
      146
      NOTE. Values are reported as time of initiation following surgery (in weeks unless otherwise specified). Brace duration is reported as total number of weeks of brace use.
      NR, study reported use of regimen but did not specify initiation time; ROM, range of motion; –, rehab modality was not mentioned.

      Modified Coleman Methodology Score

      Table 5 shows the MCMS scores from the 25 included studies. Six studies
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      ,
      • Ebert J.R.
      • Fallon M.
      • Robertson W.B.
      • et al.
      Radiological assessment of accelerated versus traditional approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation.
      ,
      • Ebert J.R.
      • Fallon M.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.R.
      A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: Findings at 5 years.
      ,
      • Ibarra C.
      • Villalobos E.
      • Madrazo-Ibarra A.
      • et al.
      Arthoscopic matrix-assisted autologous chondrocyte transplantation versus microfracture: A 6-year follow-up of a prospective randomized trial.
      ,
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      Safety and efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology is independent of spheroid dose after 4 years.
      ,
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      A prospective, randomized, open-label, multicenter, Phase III noninferiority trial to compare the clinical efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology versus arthroscopic microfracture for cartilage defects of the knee.
      received an excellent score, 17 studies
      • Brittberg M.
      • Recker D.
      • Ilgenfritz J.
      • Saris D.B.F.
      SUMMIT Extension Study Group. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: Five-year follow-up of a prospective randomized trial.
      ,
      • Ebert J.R.
      • Edwards P.K.
      • Fallon M.
      • Ackland T.R.
      • Janes G.C.
      • Wood D.J.
      Two-year outcomes of a randomized trial investigating a 6-week return to full weightbearing after matrix-induced autologous chondrocyte implantation.
      ,
      • 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.
      • Wondrasch B.
      • Risberg M.A.
      • Zak L.
      • Marlovits S.
      • Aldrian S.
      Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle: a prospective, randomized controlled study presenting MRI-based and clinical outcomes after 5 years.
      • Wondrasch B.
      • Zak L.
      • Welsch G.H.
      • 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.
      • Akgun I.
      • Unlu M.C.
      • Erdal O.A.
      • et al.
      Matrix-induced autologous mesenchymal stem cell implantation versus matrix-induced autologous chondrocyte implantation in the treatment of chondral defects of the knee: A 2-year randomized study.
      • Barié A.
      • Kruck P.
      • Sorbi R.
      • et al.
      Prospective long-term follow-up of autologous chondrocyte implantation with periosteum versus matrix-associated autologous chondrocyte implantation: A randomized clinical trial.
      • Basad E.
      • Ishaque B.
      • Bachmann G.
      • Stürz H.
      • Steinmeyer J.
      Matrix-induced autologous chondrocyte implantation versus microfracture in the treatment of cartilage defects of the knee: A 2-year randomised study.
      • Clavé A.
      • Potel J.F.
      • Servien E.
      • et al.
      Third-generation autologous chondrocyte implantation versus mosaicplasty for knee cartilage injury: 2-year randomized trial.
      • 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.
      • Ebert J.R.
      • Fallon M.
      • Ackland T.R.
      • Janes G.C.
      • Wood D.J.
      Minimum 10-year clinical and radiological outcomes of a randomized controlled trial evaluating 2 different approaches to full weightbearing after matrix-induced autologous chondrocyte implantation.
      ,
      • Ebert J.R.
      • Lloyd D.G.
      • Ackland T.
      • Wood D.J.
      Knee biomechanics during walking gait following matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      A prospective, randomized comparison of traditional and accelerated approaches to postoperative rehabilitation following autologous chondrocyte implantation: 2-year clinical outcomes.
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      Traditional vs accelerated approaches to post-operative rehabilitation following matrix-induced autologous chondrocyte implantation (MACI): Comparison of clinical, biomechanical and radiographic outcomes.
      ,
      • Hoburg A.
      • Niemeyer P.
      • Laute V.
      • et al.
      Matrix-associated autologous chondrocyte implantation with spheroid technology is superior to arthroscopic microfracture at 36 months regarding activities of daily living and sporting activities after treatment.
      ,
      • Liu Y.L.
      • Yen C.C.
      • Liu T.T.
      • et al.
      Safety and efficacy of Kartigen® in treating cartilage defects: A randomized, controlled, phase I trial.
      ,
      • Zeifang F.
      • Oberle D.
      • Nierhoff C.
      • et al.
      Autologous chondrocyte implantation using the original periosteum-cover technique versus matrix-associated autologous chondrocyte implantation: A randomized clinical trial.
      received a good score, and 2 studies
      • Edwards P.K.
      • Ackland T.R.
      • Ebert J.R.
      Accelerated weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint: Early clinical and radiological outcomes.
      ,
      • Fossum V.
      • Hansen A.K.
      • Wilsgaard T.
      • Knutsen G.
      Collagen-covered autologous chondrocyte implantation versus autologous matrix-induced chondrogenesis: A randomized trial comparing 2 methods for repair of cartilage defects of the knee.
      received a fair score.
      Table 5Modified Coleman Methodology Score (MCMS)
      StudyMCMS
      Akgun et al., 2014
      • Akgun I.
      • Unlu M.C.
      • Erdal O.A.
      • et al.
      Matrix-induced autologous mesenchymal stem cell implantation versus matrix-induced autologous chondrocyte implantation in the treatment of chondral defects of the knee: A 2-year randomized study.
      75
      Barie et al., 2020
      • Barié A.
      • Kruck P.
      • Sorbi R.
      • et al.
      Prospective long-term follow-up of autologous chondrocyte implantation with periosteum versus matrix-associated autologous chondrocyte implantation: A randomized clinical trial.
      76
      Basad et al., 2010
      • Basad E.
      • Ishaque B.
      • Bachmann G.
      • Stürz H.
      • Steinmeyer J.
      Matrix-induced autologous chondrocyte implantation versus microfracture in the treatment of cartilage defects of the knee: A 2-year randomised study.
      82
      Brittberg et al., 2018
      • Brittberg M.
      • Recker D.
      • Ilgenfritz J.
      • Saris D.B.F.
      SUMMIT Extension Study Group. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: Five-year follow-up of a prospective randomized trial.
      81
      Clavé et al., 2016
      • Clavé A.
      • Potel J.F.
      • Servien E.
      • et al.
      Third-generation autologous chondrocyte implantation versus mosaicplasty for knee cartilage injury: 2-year randomized trial.
      82
      Crawford et al., 2012
      • 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.
      79
      Ebert et al., 2012
      • Ebert J.R.
      • Fallon M.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.R.
      A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: Findings at 5 years.
      91
      Ebert et al., 2021
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      88
      Ebert et al., 2011
      • Ebert J.R.
      • Fallon M.
      • Robertson W.B.
      • et al.
      Radiological assessment of accelerated versus traditional approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation.
      85
      Ebert et al., 2017
      • Ebert J.R.
      • Edwards P.K.
      • Fallon M.
      • Ackland T.R.
      • Janes G.C.
      • Wood D.J.
      Two-year outcomes of a randomized trial investigating a 6-week return to full weightbearing after matrix-induced autologous chondrocyte implantation.
      82
      Ebert et al., 2020
      • Ebert J.R.
      • Fallon M.
      • Ackland T.R.
      • Janes G.C.
      • Wood D.J.
      Minimum 10-year clinical and radiological outcomes of a randomized controlled trial evaluating 2 different approaches to full weightbearing after matrix-induced autologous chondrocyte implantation.
      82
      Ebert et al., 2010
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      A prospective, randomized comparison of traditional and accelerated approaches to postoperative rehabilitation following autologous chondrocyte implantation: 2-year clinical outcomes.
      81
      Ebert et al., 2010
      • Ebert J.R.
      • Lloyd D.G.
      • Ackland T.
      • Wood D.J.
      Knee biomechanics during walking gait following matrix-induced autologous chondrocyte implantation.
      80
      Ebert et al., 2008
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      Traditional vs accelerated approaches to post-operative rehabilitation following matrix-induced autologous chondrocyte implantation (MACI): Comparison of clinical, biomechanical and radiographic outcomes.
      80
      Edwards et al., 2013
      • Edwards P.K.
      • Ackland T.R.
      • Ebert J.R.
      Accelerated weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint: Early clinical and radiological outcomes.
      69
      Fossum et al., 2019
      • Fossum V.
      • Hansen A.K.
      • Wilsgaard T.
      • Knutsen G.
      Collagen-covered autologous chondrocyte implantation versus autologous matrix-induced chondrogenesis: A randomized trial comparing 2 methods for repair of cartilage defects of the knee.
      69
      Hoburg et al., 2020
      • Hoburg A.
      • Niemeyer P.
      • Laute V.
      • et al.
      Matrix-associated autologous chondrocyte implantation with spheroid technology is superior to arthroscopic microfracture at 36 months regarding activities of daily living and sporting activities after treatment.
      80
      Ibarra et al., 2021
      • Ibarra C.
      • Villalobos E.
      • Madrazo-Ibarra A.
      • et al.
      Arthoscopic matrix-assisted autologous chondrocyte transplantation versus microfracture: A 6-year follow-up of a prospective randomized trial.
      85
      Liu et al., 2021
      • Liu Y.L.
      • Yen C.C.
      • Liu T.T.
      • et al.
      Safety and efficacy of Kartigen® in treating cartilage defects: A randomized, controlled, phase I trial.
      70
      Niemeyer et al., 2019
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      A prospective, randomized, open-label, multicenter, Phase III noninferiority trial to compare the clinical efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology versus arthroscopic microfracture for cartilage defects of the knee.
      88
      Niemeyer et al., 2020
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      Safety and efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology is independent of spheroid dose after 4 years.
      85
      Saris et al., 2014
      • 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.
      78
      Wondrasch et al., 2009
      • Wondrasch B.
      • Zak L.
      • Welsch G.H.
      • 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.
      82
      Wondrasch et al., 2015
      • Wondrasch B.
      • Risberg M.A.
      • Zak L.
      • Marlovits S.
      • Aldrian S.
      Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle: a prospective, randomized controlled study presenting MRI-based and clinical outcomes after 5 years.
      81
      Zeifang et al., 2010
      • Zeifang F.
      • Oberle D.
      • Nierhoff C.
      • et al.
      Autologous chondrocyte implantation using the original periosteum-cover technique versus matrix-associated autologous chondrocyte implantation: A randomized clinical trial.
      75

      Methodologic Quality Assessment

      The results of the methodologic quality assessment of included studies using the Cochrane Collaboration’s risk of bias tool are presented in Figure 2. Sequence generation and allocation were adequately reported by most studies,
      • Ebert J.R.
      • Edwards P.K.
      • Fallon M.
      • Ackland T.R.
      • Janes G.C.
      • Wood D.J.
      Two-year outcomes of a randomized trial investigating a 6-week return to full weightbearing after matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      • 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.
      • Wondrasch B.
      • Risberg M.A.
      • Zak L.
      • Marlovits S.
      • Aldrian S.
      Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle: a prospective, randomized controlled study presenting MRI-based and clinical outcomes after 5 years.
      • Wondrasch B.
      • Zak L.
      • Welsch G.H.
      • 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.
      • Akgun I.
      • Unlu M.C.
      • Erdal O.A.
      • et al.
      Matrix-induced autologous mesenchymal stem cell implantation versus matrix-induced autologous chondrocyte implantation in the treatment of chondral defects of the knee: A 2-year randomized study.
      • Barié A.
      • Kruck P.
      • Sorbi R.
      • et al.
      Prospective long-term follow-up of autologous chondrocyte implantation with periosteum versus matrix-associated autologous chondrocyte implantation: A randomized clinical trial.
      • Basad E.
      • Ishaque B.
      • Bachmann G.
      • Stürz H.
      • Steinmeyer J.
      Matrix-induced autologous chondrocyte implantation versus microfracture in the treatment of cartilage defects of the knee: A 2-year randomised study.
      • Clavé A.
      • Potel J.F.
      • Servien E.
      • et al.
      Third-generation autologous chondrocyte implantation versus mosaicplasty for knee cartilage injury: 2-year randomized trial.
      • 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.
      • Ebert J.R.
      • Fallon M.
      • Ackland T.R.
      • Janes G.C.
      • Wood D.J.
      Minimum 10-year clinical and radiological outcomes of a randomized controlled trial evaluating 2 different approaches to full weightbearing after matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Fallon M.
      • Robertson W.B.
      • et al.
      Radiological assessment of accelerated versus traditional approaches to postoperative rehabilitation following matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Fallon M.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.R.
      A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: Findings at 5 years.
      • Ebert J.R.
      • Lloyd D.G.
      • Ackland T.
      • Wood D.J.
      Knee biomechanics during walking gait following matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      A prospective, randomized comparison of traditional and accelerated approaches to postoperative rehabilitation following autologous chondrocyte implantation: 2-year clinical outcomes.
      • Ebert J.R.
      • Robertson W.B.
      • Lloyd D.G.
      • Zheng M.H.
      • Wood D.J.
      • Ackland T.
      Traditional vs accelerated approaches to post-operative rehabilitation following matrix-induced autologous chondrocyte implantation (MACI): Comparison of clinical, biomechanical and radiographic outcomes.
      • Edwards P.K.
      • Ackland T.R.
      • Ebert J.R.
      Accelerated weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint: Early clinical and radiological outcomes.
      ,
      • Hoburg A.
      • Niemeyer P.
      • Laute V.
      • et al.
      Matrix-associated autologous chondrocyte implantation with spheroid technology is superior to arthroscopic microfracture at 36 months regarding activities of daily living and sporting activities after treatment.
      ,
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      Safety and efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology is independent of spheroid dose after 4 years.
      • Niemeyer P.
      • Laute V.
      • Zinser W.
      • et al.
      A prospective, randomized, open-label, multicenter, Phase III noninferiority trial to compare the clinical efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology versus arthroscopic microfracture for cartilage defects of the knee.
      • Zeifang F.
      • Oberle D.
      • Nierhoff C.
      • et al.
      Autologous chondrocyte implantation using the original periosteum-cover technique versus matrix-associated autologous chondrocyte implantation: A randomized clinical trial.
      except in 4 studies,
      • Brittberg M.
      • Recker D.
      • Ilgenfritz J.
      • Saris D.B.F.
      SUMMIT Extension Study Group. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: Five-year follow-up of a prospective randomized trial.
      ,
      • Fossum V.
      • Hansen A.K.
      • Wilsgaard T.
      • Knutsen G.
      Collagen-covered autologous chondrocyte implantation versus autologous matrix-induced chondrogenesis: A randomized trial comparing 2 methods for repair of cartilage defects of the knee.
      ,
      • Ibarra C.
      • Villalobos E.
      • Madrazo-Ibarra A.
      • et al.
      Arthoscopic matrix-assisted autologous chondrocyte transplantation versus microfracture: A 6-year follow-up of a prospective randomized trial.
      ,
      • Liu Y.L.
      • Yen C.C.
      • Liu T.T.
      • et al.
      Safety and efficacy of Kartigen® in treating cartilage defects: A randomized, controlled, phase I trial.
      in which the concealment of allocation from the investigators was unclear (unclear risk of bias). Fourteen studies
      • Ebert J.R.
      • Edwards P.K.
      • Fallon M.
      • Ackland T.R.
      • Janes G.C.
      • Wood D.J.
      Two-year outcomes of a randomized trial investigating a 6-week return to full weightbearing after matrix-induced autologous chondrocyte implantation.
      • Ebert J.R.
      • Fallon M.
      • Wood D.J.
      • Janes G.C.
      An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery.
      • 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.
      • Wondrasch B.
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