title: Mechanical stimulation enhances integration in an in vitro model of cartilage repair.
abstract: OBJECTIVE
  (1) To characterize the effects of mechanical stimulation on the integration of a tissue-engineered construct in terms of histology, biochemistry and biomechanical properties; (2) to identify whether cells of the implant or host tissue were critical to implant integration; and (3) to study cells believed to be involved in lateral integration of tissue-engineered cartilage to host cartilage. We hypothesized that mechanical stimulation would enhance the integration of the repair implant with host cartilage in an in vitro integration model.
  
  
  METHODS
  Articular cartilage was harvested from 6- to 9-month-old bovine metacarpal-phalangeal joints. Constructs composed of tissue-engineered cartilage implanted into host cartilage were placed in spinner bioreactors and maintained on a magnetic stir plate at either 0 (static control) or 90 (experimental) rotations per minute (RPM). The constructs from both the static and spinner bioreactors were harvested after either 2 or 4 weeks of culture and evaluated histologically, biochemically, biomechanically and for gene expression.
  
  
  RESULTS
  The extent and strength of integration between tissue-engineered cartilage and native cartilage improved significantly with both time and mechanical stimulation. Integration did not occur if the implant was not viable. The presence of stimulation led to a significant increase in collagen content in the integration zone between host and implant at 2 weeks. The gene profile of cells in the integration zone differs from host cartilage demonstrating an increase in the expression of membrane type 1 matrix metalloproteinase (MT1-MMP), aggrecan and type II collagen.
  
  
  CONCLUSIONS
  This study shows that the integration of in vitro tissue-engineered implants with host tissue improves with mechanical stimulation. The findings of this study suggests that consideration should be given to implementing early loading (mechanical stimulation) into future in vivo studies investigating the long-term viability and integration of tissue-engineered cartilage for the treatment of cartilage injuries. This could simply be done through the use of continuous passive motion (CPM) in the post-operative period or through a more complex and structured rehabilitation program with a gradual increase in forces across the joint over time.
authors.affiliation: University of Toronto Orthopaedic Sports Medicine Program, Mount Sinai Hospital and Women's College Hospital, Room 476C, 600 University Ave, Toronto, ON, M5G 1X5, Canada. JTheodoropoulos@mtsinai.on.ca.
authors.forename: John S
authors.initials: JS
authors.lastname: Theodoropoulos
authors.affiliation: Bioengineering of Skeletal Tissues Team, Division of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave, Toronto, ON, M5G 1X5, Canada.
authors.forename: Amritha J N
authors.initials: AJ
authors.lastname: DeCroos
authors.affiliation: University of Toronto Orthopaedic Sports Medicine Program, Mount Sinai Hospital and Women's College Hospital, Room 476C, 600 University Ave, Toronto, ON, M5G 1X5, Canada.
authors.forename: Massimo
authors.initials: M
authors.lastname: Petrera
authors.affiliation: University of Toronto Orthopaedic Sports Medicine Program, Mount Sinai Hospital and Women's College Hospital, Room 476C, 600 University Ave, Toronto, ON, M5G 1X5, Canada.
authors.forename: Sam
authors.initials: S
authors.lastname: Park
authors.affiliation: Bioengineering of Skeletal Tissues Team, Division of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave, Toronto, ON, M5G 1X5, Canada.
authors.forename: Rita A
authors.initials: RA
authors.lastname: Kandel
mesh_terms: D053674:Aggrecans / Q000378:metabolism; D000818:Animals; D019149:Bioreactors; D002358:Cartilage, Articular / Q000378:metabolism / Q000601:surgery*; D002417:Cattle; D020219:Chondrogenesis; D024043:Collagen Type II / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D013314:Stress, Mechanical; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D053674:Aggrecans; D024043:Collagen Type II; D020781:Matrix Metalloproteinase 1
keywords: Cartilage integration; Cartilage repair; Mechanical stimulation; Tissue-engineered cartilage