title: Defect type, localization and marker gene expression determines early adverse events of matrix-associated autologous chondrocyte implantation.
abstract: BACKGROUND
  Since the first description of autologous chondrocyte implantation (ACI) in 1994 different methods and improvements were established for this regenerative treatment option of large chondral defects. This study analyzes safety and short-term clinical results from characterized ACI using a collagen based biphasic scaffold and evaluates prognostic factors.
  
  
  METHODS
  433 patients with a mean age of 33.4 years and localized grade III to IV cartilage defects (ICRS classification) in the knee or ankle were included. Mean defect size was 5.9 cm(2). Prior seeding of the scaffold, expanded chondrocytes were characterized by RT-PCR on 6 different marker genes (type I and II collagen, aggrecan, interleukin-1 β (IL-1β), vascular endothelial growth factor receptor 1 (FLT-1) and bone sialoprotein-2 (BSP-2)). Clinical outcome was evaluated using a questionnaire for defect history, basic demographics, time elapsed from surgery, 10-point outcome assessments of pain, function and swelling. Moreover, adverse events (AEs) or subsequent treatments were recorded and analysed.
  
  
  RESULTS
  Patients improved significantly over baseline (p < 0.0001) in pain, function and swelling. Subjects with later than 12 months follow-up reported nominally greater mean changes. Graft failure incidence was 6% for patients with greater than one year follow-up. Graft-related complications were significantly higher for patellar (p < 0.0001) and degenerative defects (p = 0.005). Elevated expression of FLT-1 (p = 0.02) or IL-1 β mRNA (p = 0.03) was associated with graft-related AEs. A borderline association was found for low collagen type II expression (p = 0.08).
  
  
  CONCLUSIONS
  Early graft-related AEs after ACI with a biphasic collagen scaffold are related to defect type, location and marker gene expression. The levels of significance observed for gene expression with respect to graft-related AEs were subordinate to those identified in the analysis of lesion history and location.
authors.affiliation: Department of Trauma Surgery, University Medical Centre Regensburg, Germany; Sporthopaedicum Regensburg, Germany. Electronic address: peter.angele@ukr.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Angele
authors.affiliation: Orthopädisch Chirurgisches Zentrum Tübingen, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Fritz
authors.affiliation: Klinik im Kronprinzenbau, Reutlingen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Albrecht
authors.affiliation: Department of Orthopaedic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Koh
authors.affiliation: Department of Trauma Surgery, University Medical Centre Regensburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Zellner
mesh_terms: D000328:Adult; D016512:Ankle Injuries / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D002357:Cartilage Diseases / Q000503:physiopathology / Q000628:therapy*; D002358:Cartilage, Articular; D017690:Cell Transplantation; D019902:Chondrocytes / Q000637:transplantation*; D024042:Collagen Type I / Q000378:metabolism; D005260:Female; D006085:Graft Survival; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D007718:Knee Injuries / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D016059:Range of Motion, Articular; D020127:Recovery of Function; D012189:Retrospective Studies; D014182:Transplantation, Autologous; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D053583:Interleukin-1beta; D042461:Vascular Endothelial Growth Factor A
keywords: MACT; adverse events; cartilage defect; cell characterization; short-term clinical outcome