title: Physical stimulation of chondrogenic cells in vitro: a review.
abstract: BACKGROUND
  Mechanical stimuli are of crucial importance for the development and maintenance of articular cartilage. For conditioning of cartilaginous tissues, various bioreactor systems have been developed that have mainly aimed to produce cartilaginous grafts for tissue engineering applications. Emphasis has been on in vitro preconditioning, whereas the same devices could be used to attempt to predict the response of the cells in vivo or as a prescreening method before animal studies. As a result of the complexity of the load and motion patterns within an articulating joint, no bioreactor can completely recreate the in vivo situation.
  
  
  OBJECTIVE
  This article aims to classify the various loading bioreactors into logical categories, highlight the response of mesenchymal stem cells and chondrocytes to the various stimuli applied, and determine which data could be used within a clinical setting.
  
  
  METHODS
  We performed a Medline search using specific search terms, then selectively reviewed relevant research relating to physical stimulation of chondrogenic cells in vitro, focusing on cellular responses to the specific load applied.
  
  
  RESULTS
  There is much data pertaining to increases in chondrogenic gene expression as a result of controlled loading protocols. Uniaxial loading leads to selective upregulation of genes normally associated with a chondrogenic phenotype, whereas multiaxial loading results in a broader pattern of chondrogenic gene upregulation. The potential for the body to be used as an in vivo bioreactor is being increasingly explored.
  
  
  CONCLUSIONS
  Bioreactors are important tools for understanding the potential response of chondrogenic cells within the joint environment. However, to replicate the natural in vivo situation, more complex motion patterns are required to induce more physiological chondrogenic gene upregulation.
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos Platz, Switzerland.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Grad
authors.forename: David
authors.initials: D
authors.lastname: Eglin
authors.forename: Mauro
authors.initials: M
authors.lastname: Alini
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Stoddart
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D019149:Bioreactors; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D020219:Chondrogenesis / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000235:genetics; D010812:Physical Stimulation; D046509:Tissue Culture Techniques