title: Extracellular Matrix Deposition in Engineered Micromass Cartilage Pellet Cultures: Measurements and Modelling.
abstract: This article explores possible mechanisms governing extracellular matrix deposition in engineered cartilaginous cell pellets. A theoretical investigation is carried out alongside an experimental study measuring proteoglycan and collagen volume fractions within murine chondrogenic (ATDC-5) cell pellets. The simple mathematical model, which adopts a nutrient-dependent proteoglycan production rate, successfully reproduces the periphery-dominated proteoglycan deposition, characteristic of the growth pattern observed experimentally within pellets after 21 days of culture. The results suggest that this inhomogeneous proteoglycan production is due to nutrient deficiencies at the pellet centre. Our model analysis further indicates that a spatially uniform distribution of proteoglycan matrix could be maintained by initiating the culture process with a smaller-sized pellet. Finally, possible extensions are put forward with an aim to improve the model predictions for the early behaviour, where different mechanisms appear to dominate the matrix production within the pellets.
authors.affiliation: Mathematical Sciences, University of Southampton, Southampton, SO17 1BJ, United Kingdom.
authors.forename: Miranda C
authors.initials: MC
authors.lastname: Lewis
authors.affiliation: Mathematical Sciences, University of Southampton, Southampton, SO17 1BJ, United Kingdom.|Centre for Human Development, Stem Cells and Regeneration, Faculty of Medicine, University of Southampton, Southampton, SO16 6YD, United Kingdom.
authors.forename: Ben D
authors.initials: BD
authors.lastname: MacArthur
authors.affiliation: Centre for Human Development, Stem Cells and Regeneration, Faculty of Medicine, University of Southampton, Southampton, SO16 6YD, United Kingdom.
authors.forename: Rahul S
authors.initials: RS
authors.lastname: Tare
authors.affiliation: Centre for Human Development, Stem Cells and Regeneration, Faculty of Medicine, University of Southampton, Southampton, SO16 6YD, United Kingdom.
authors.forename: Richard O C
authors.initials: RO
authors.lastname: Oreffo
authors.affiliation: Mathematical Institute, University of Oxford, Oxford, OX2 6GG, United Kingdom.
authors.forename: Colin P
authors.initials: CP
authors.lastname: Please
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology* / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002460:Cell Line; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D003094:Collagen / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000378:metabolism*; D051379:Mice; D015233:Models, Statistical; D011509:Proteoglycans / Q000096:biosynthesis; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D011509:Proteoglycans; D003094:Collagen