title: Chondroinduction Is the Main Cartilage Repair Response to Microfracture and Microfracture With BST-CarGel: Results as Shown by ICRS-II Histological Scoring and a Novel Zonal Collagen Type Scoring Method of Human Clinical Biopsy Specimens.
abstract: BACKGROUND
  Current cartilage repair histological scoring systems are unable to explain the relationship between collagen type II deposition and overall repair quality.
  
  
  OBJECTIVE
  The purpose of this study was to develop a novel zonal collagen type (ZCT) 5-point scoring system to measure chondroinduction in human clinical biopsy specimens collected after marrow stimulation. The hypothesis was that the ZCT scores would correlate with the International Cartilage Repair Society-II (ICRS-II) overall histological repair assessment score and glycosaminoglycan (GAG) content.
  
  
  METHODS
  Descriptive laboratory study.
  
  
  METHODS
  After optimizing safranin O staining for GAG and immunostaining for human collagen type II and type I (Col2 and Col1, respectively), serial sections from clinical osteochondral repair biopsy specimens (13 months after microfracture or microfracture with BST-CarGel; n = 39 patients) were stained and 3 blinded readers performed histomorphometry for percentage of staining, ICRS-II histological scoring, polarized light microscopy (PLM) scoring, and 5-point ZCT scoring based on tidemark morphology, zonal distribution of Col2 and Col1, and Col1 percentage stain. Because 1 biopsy specimen was missing bone, 38 biopsy specimens were evaluated for ICRS-II, PLM, and ZCT scores.
  
  
  RESULTS
  Chondroinduction was identified in 21 biopsy specimens as a Col2 matrix fused to bone that spanned the deep-middle-superficial zones ("full-thickness hyaline repair"), deep-middle zones, or deep zone ("stalled hyaline") that was covered with a variable-thickness Col1-positive matrix, and was scored, respectively, as ZCT = 1 (n = 4 biopsy specimens), ZCT = 2 (n = 6) and ZCT = 3 (n = 11). Other biopsy specimens (n = 17) were fibrocartilage (n = 9; ZCT = 4), fibrous tissue (n = 4, ZCT = 5), or non-marrow derived (n = 4; ZCT = 0). Non-marrow derived tissue had a mean mature tidemark score of 84 out of 100 versus a regenerating tidemark score of 24 for all other biopsy specimens (P = .005). Both "stalled hyaline" repair and fibrocartilage had the same mean Col2 percentage stain; however, fibrocartilage was distinguished by heavy Col1 deposits in the deep zone, a 2-fold higher mean Col1 percentage stain (P = .001), and lower surface integrity (P = .03). ZCT scores correlated with GAG content and the ICRS-II overall assessment score, especially when combined with the PLM score for collagen organization (R = 0.82). Histological scores of the deep zone strongly predicted the ICRS-II overall assessment score (R = 0.99).
  
  
  CONCLUSIONS
  The ICRS-II overall repair assessment score and GAG content correlated with the extent of Col2 deposition free of fibrosis in the deep/middle zone rather than bulk accumulation of Col2.
  
  
  CONCLUSIONS
  Biopsy tissue from the BST-CarGel randomized clinical trial (microfracture without and with BST-CarGel, as treatment groups were not unblinded) showed regenerated tissue consistent with a chondroinduction mechanism in at least half of the treated lesions.
authors.affiliation: Department of Chemical Engineering, École Polytechnique, Montréal, Québec, Canada Institute of Biomedical Engineering, École Polytechnique, Montréal, Québec, Canada c.hoemann@polymtl.ca.
authors.forename: Caroline D
authors.initials: CD
authors.lastname: Hoemann
authors.affiliation: Department of Chemical Engineering, École Polytechnique, Montréal, Québec, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tran-Khanh
authors.affiliation: Department of Chemical Engineering, École Polytechnique, Montréal, Québec, Canada.
authors.forename: Anik
authors.initials: A
authors.lastname: Chevrier
authors.affiliation: Department of Chemical Engineering, École Polytechnique, Montréal, Québec, Canada.
authors.forename: Gaoping
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Chemical Engineering, École Polytechnique, Montréal, Québec, Canada.
authors.forename: Viorica
authors.initials: V
authors.lastname: Lascau-Coman
authors.affiliation: Department of Chemical Engineering, École Polytechnique, Montréal, Québec, Canada.
authors.forename: Colleen
authors.initials: C
authors.lastname: Mathieu
authors.affiliation: Institute of Biomedical Engineering, École Polytechnique, Montréal, Québec, Canada.
authors.forename: Adele
authors.initials: A
authors.lastname: Changoor
authors.affiliation: Vital Systems Inc, Rolling Meadows, Illinois, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Yaroshinsky
authors.affiliation: Department of Orthopaedic Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Robert G
authors.initials: RG
authors.lastname: McCormack
authors.affiliation: Orthopaedic and Sport Medicine Clinic of Nova Scotia, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: William D
authors.initials: WD
authors.lastname: Stanish
authors.affiliation: Department of Chemical Engineering, École Polytechnique, Montréal, Québec, Canada Institute of Biomedical Engineering, École Polytechnique, Montréal, Québec, Canada.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Buschmann
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy / Q000379:methods*; D002358:Cartilage, Articular / Q000293:injuries / Q000378:metabolism / Q000473:pathology*; D003094:Collagen / Q000378:metabolism*; D005260:Female; D051445:Fibrocartilage / Q000378:metabolism / Q000473:pathology; D015725:Fluconazole; D050723:Fractures, Bone / Q000378:metabolism / Q000473:pathology*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D007718:Knee Injuries / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D014945:Wound Healing; D055815:Young Adult
chemical_list: D006025:Glycosaminoglycans; D015725:Fluconazole; D003094:Collagen
keywords: cartilage repair; cartilage resurfacing; human clinical biopsy; knee articular cartilage; tidemark; zonal collagen scoring system