title: Magnetic Resonance Imaging Characterization and Clinical Outcomes After NeoCart Surgical Therapy as a Primary Reparative Treatment for Knee Cartilage Injuries.
abstract: BACKGROUND
  Autologous cartilage tissue implants, including the NeoCart implant, are intended to repair focal articular cartilage lesions. Short-term results from United States Food and Drug Administration (FDA) phase I and phase II clinical trials indicated that the NeoCart implant was safe when surgically applied as a cell-based therapy and efficacious compared with microfracture.
  
  
  OBJECTIVE
  Quantitative magnetic resonance imaging (MRI) analysis would reveal NeoCart tissue maturation through to 60-month follow-up.
  
  
  METHODS
  Case series; Level of evidence, 4.
  
  
  METHODS
  Patients with symptomatic full-thickness cartilage lesions of the distal femoral condyle were treated with NeoCart in FDA clinical trials. Safety and efficacy were evaluated prospectively by MRI and clinical patient-reported outcomes (PROs) through to 60-month follow-up. Qualitative MRI metrics were quantified according to modified MOCART (magnetic resonance observation of cartilage repair tissue) criteria, with an independent evaluation of repair tissue signal intensity. Subjective PROs and objective range of motion (ROM) were obtained at baseline and through to 60 months.
  
  
  RESULTS
  Twenty-nine patients treated with NeoCart were observed over a mean of 52.0 ± 15.5 months (median, 60 months). MOCART analyses indicated significant improvement ( P < .001) in cartilage quality from 3 to 24 months, with stabilization from 24 to 60 months. Signal intensity of the repair tissue evolved from hyperintense at early follow-up to isointense after 6 months and to hypointense after 24 months. The temporal progression toward hypointense T2 signals at later time points observed here indicated a further reorganization of the repair tissue toward a dense tissue that was less similar to the surrounding native tissue. However, 80% of patients showed evidence of subchondral bone changes on MRI at all time points; 4 patients (14%) showed no improvement of MRI criteria. Compared with baseline values, significant improvement ( P < .001) was seen in PROs (mean [±SD] baseline to mean [±SD] final follow-up), including the International Knee Documentation Committee score (47.9 ± 17.4 to 75.5 ± 22.1), physical component summary of the Short Form-36 (40.5 ± 7.2 to 51.4 ± 8.1), and all 5 domains of the Knee injury and Osteoarthritis Outcome Score (Pain: 64.8 ± 12.1 to 86.1 ± 17.3; Activities of Daily Living: 75.5 ± 14.8 to 91.6 ± 13.8; Quality of Life: 28.6 ± 15.5 to 69.4 ± 28.0; Symptoms: 65.8 ± 13.8 to 86.6 ± 13.4; Sports and Recreation: 41.4 ± 24.3 to 72.4 ± 28.8). Significant ( P < .0001) decreases from baseline scores for the visual analog scale for pain (34.6 ± 22.5) were seen by 6 months and sustained at final follow-up (14.3 ± 18.4). ROM significantly ( P < .0001) improved from baseline (131.5° ± 7.9°) to final follow-up (140.7° ± 6.3°).
  
  
  CONCLUSIONS
  Longitudinal MRI analysis demonstrated that NeoCart-based repair tissue is durable and evolves over time. For a majority of patients, this progression trended from an initial hyperintense signal to a hypointense signal at later follow-ups. Changes in radiographic measures over time corresponded with improvement in clinical measures, with maximum benefits experienced at 24-month follow-up. Similarly, clinical efficacy for the total cohort, determined by clinical outcome scores, reached a maximum at 24 months without decline to 60 months. Results from safety and exploratory clinical trials indicate that NeoCart is a safe and effective treatment for articular cartilage lesions through to 5-year follow-up. Registration: NCT00548119 ( ClinicalTrials.gov identifier).
authors.affiliation: Department of Orthopaedics & Rehabilitation, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: Devon E
authors.initials: DE
authors.lastname: Anderson
authors.affiliation: Sports Medicine Service/Institute for Cartilage Repair, Hospital for Special Surgery, New York, New York, USA.
authors.forename: Riley J
authors.initials: RJ
authors.lastname: Williams
authors.affiliation: Department of Orthopaedic Surgery, University of Connecticut, Farmington, Connecticut, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: DeBerardino
authors.affiliation: Duke Sports Medicine Center, Duke University, Durham, North Carolina, USA.
authors.forename: Dean C
authors.initials: DC
authors.lastname: Taylor
authors.affiliation: Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, California, USA.
authors.forename: C Benjamin
authors.initials: CB
authors.lastname: Ma
authors.affiliation: Department of Orthopaedics & Rehabilitation, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: Marie S
authors.initials: MS
authors.lastname: Kane
authors.affiliation: Department of Orthopaedics & Rehabilitation, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: Dennis C
authors.initials: DC
authors.lastname: Crawford
mesh_terms: D000203:Activities of Daily Living; D000328:Adult; D002356:Cartilage / Q000637:transplantation*; D002358:Cartilage, Articular / Q000000981:diagnostic imaging / Q000293:injuries*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007718:Knee Injuries / Q000000981:diagnostic imaging* / Q000601:surgery*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D011446:Prospective Studies; D011788:Quality of Life; D016059:Range of Motion, Articular; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D064232:Visual Analog Scale; D014945:Wound Healing; D055815:Young Adult
keywords: MOCART; MRI; NeoCart; articular cartilage; autologous cartilage repair; clinical assessment; knee