title: Role of oxygen as a regulator of stem cell fate during the spontaneous repair of osteochondral defects.
abstract: The complexity of the in vivo environment makes it is difficult to isolate the effects of specific cues on regulating cell fate during regenerative events such as osteochondral defect repair. The objective of this study was to develop a computational model to explore how joint specific environmental factors regulate mesenchymal stem cell (MSC) fate during osteochondral defect repair. To this end, the spontaneous repair process within an osteochondral defect was simulated using a tissue differentiation algorithm which assumed that MSC fate was regulated by local oxygen levels and substrate stiffness. The developed model was able to predict the main stages of tissue formation observed by a number of in vivo studies. Following this, a parametric study was conducted to better understand why interventions that modulate angiogenesis dramatically impact the outcome of osteochondral defect healing. In the simulations where angiogenesis was reduced, by week 12, the subchondral plate was predicted to remain below the native tidemark, although the chondral region was composed entirely of cartilage and fibrous tissue. In the simulations where angiogenesis was increased, more robust cell proliferation and cartilage formation were observed during the first 4 weeks, however, by week 12 the subchondral plate had advanced above the native tidemark although any remaining tissue was either hypertrophic cartilage or fibrous tissue. These results suggest that osteochondral defect repair could be enhanced by interventions where angiogenesis is promoted but confined to within the subchondral region of the defect. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1026-1036, 2016.
authors.affiliation: Trinity Centre for Bioengineering, Trinity Biomedical Sciences, Trinity College Dublin, Dublin, Ireland.|Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland.
authors.forename: Adam
authors.initials: A
authors.lastname: O'Reilly
authors.affiliation: Trinity Centre for Bioengineering, Trinity Biomedical Sciences, Trinity College Dublin, Dublin, Ireland.|Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland.|Advanced Materials and Bioengineering Research Centre (AMBER), Royal College of Surgeons in Ireland and Trinity College Dublin, Dublin, Ireland.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Kelly
mesh_terms: D000465:Algorithms; D000818:Animals; D002356:Cartilage / Q000502:physiology; D020219:Chondrogenesis; D020342:Finite Element Analysis; D007718:Knee Injuries; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008954:Models, Biological; D018919:Neovascularization, Physiologic; D010100:Oxygen / Q000502:physiology*; D014945:Wound Healing
chemical_list: D010100:Oxygen
keywords: angiogenesis; computational modeling; osteochondral defect; oxygen; spontaneous repair