title: Instruments for reproducible setting of defects in cartilage and harvesting of osteochondral plugs for standardisation of preclinical tests for articular cartilage regeneration.
abstract: BACKGROUND
  Standardisation is required in research, so are approval procedures for advanced therapy medical products and other procedures for articular cartilage therapies. The process of creating samples needs to be reproducible. The aim of this study was to design, create and validate instruments (1) to create reproducible and accurate defects and (2) to isolate samples in the shape of osteochondral cylinders in a quick, reliable and sterile manner.
  
  
  METHODS
  Adjustable instruments were created: a crown mill with a resolution of 0.05 mm and a front mill to create defects in articular cartilage and subchondral bone. The instruments were tested on knee joints of pigs from the slaughterhouse; 48 defects were created and evaluated. A punching machine was designed to harvest osteochondral plugs. These were validated in an in vivo animal study.
  
  
  RESULTS
  The instruments respect the desired depth of 0.5 and 1.5 mm when creating the defects, depending on whether the person using the instrument is highly experienced (0.451 mm; confidence interval (CI): 0.390 mm; 0.512 mm and 1.403 mm; CI: 1.305 mm; 1.502 mm) or less so (0.369 mm; CI: 0.297 mm; 0.440 mm and 1.241 mm; CI: 1.141 mm; 1.341 mm). Eighty samples were taken from knee joints of Göttingen Minipigs with this punching technique. The time needed for the harvesting of the samples was 7.52 min (±2.18 min), the parallelism of the sides of the cylinders deviated by -0.63° (CI: -1.33°; 0.08°) and the surface of the cartilage deviated from the perpendicularity by 4.86° (CI: 4.154°; 5.573°). In all assessed cases, a sterile procedure was observed.
  
  
  CONCLUSIONS
  Instruments and procedures for standardised creation and validation of defects in articular cartilage and subchondral bone were designed. Harvesting of samples in the shape of osteochondral cylinders can now be performed in a quick, reliable and sterile manner. The presented instruments and procedures can serve as helpful steps towards standardised operating procedures in the field of regenerative therapies of articular cartilage in research and for regulatory requirements.
authors.affiliation: Section for Experimental Orthopaedics and Trauma Surgery, Orthopaedic and Trauma Surgery Centre (OUZ), University Medical Centre Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany. markus.schwarz@medma.uni-heidelberg.de.
authors.forename: Markus L
authors.initials: ML
authors.lastname: Schwarz
authors.affiliation: Section for Experimental Orthopaedics and Trauma Surgery, Orthopaedic and Trauma Surgery Centre (OUZ), University Medical Centre Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Schneider-Wald
authors.affiliation: Department of Medical Statistics, Biomathematics and Information Processing, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Brade
authors.affiliation: Section for Experimental Orthopaedics and Trauma Surgery, Orthopaedic and Trauma Surgery Centre (OUZ), University Medical Centre Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Schleich
authors.affiliation: Section for Experimental Orthopaedics and Trauma Surgery, Orthopaedic and Trauma Surgery Centre (OUZ), University Medical Centre Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
authors.forename: Andy
authors.initials: A
authors.lastname: Schütte
authors.affiliation: Section for Experimental Orthopaedics and Trauma Surgery, Orthopaedic and Trauma Surgery Centre (OUZ), University Medical Centre Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
authors.forename: Gregor
authors.initials: G
authors.lastname: Reisig
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000502:physiology; D002358:Cartilage, Articular / Q000473:pathology / Q000601:surgery*; D007719:Knee Joint / Q000473:pathology / Q000601:surgery*; D023421:Models, Animal; D013525:Surgical Instruments / Q000592:standards*; D013552:Swine; D013556:Swine, Miniature; D014182:Transplantation, Autologous / Q000379:methods