title: Scaffold architecture determines chondrocyte response to externally applied dynamic compression.
abstract: It remains unclear how specific mechanical signals generated by applied dynamic compression (DC) regulate chondrocyte biosynthetic activity. It has previously been suggested that DC-induced interstitial fluid flow positively impacts cartilage-specific matrix production. Modifying fluid flow within dynamically compressed hydrogels therefore represents a promising approach to controlling chondrocyte behavior, which could potentially be achieved by changing the construct architecture. The objective of this study was to first determine the influence of construct architecture on the mechanical environment within dynamically compressed agarose hydrogels using finite element (FE) modeling and to then investigate how chondrocytes would respond to this altered environment. To modify construct architecture, an array of channels was introduced into the hydrogels. Increased magnitudes of fluid flow were predicted in the periphery of dynamically compressed solid hydrogels and also around the channels in the dynamically compressed channeled hydrogels. DC was found to significantly increase sGAG synthesis in solid constructs, which could be attributed at least in part to an increase in DNA. DC was also found to preferentially increase collagen accumulation in regions of solid and channeled constructs where FE modeling predicted higher levels of fluid flow, suggesting that this stimulus is important for promoting collagen production by chondrocytes embedded in agarose gels. In conclusion, this study demonstrates how the architecture of cell-seeded scaffolds or hydrogels can be modified to alter the spatial levels of biophysical cues throughout the construct, leading to greater collagen accumulation throughout the engineered tissue rather than preferentially in the construct periphery. This system also provides a novel approach to investigate how chondrocytes respond to altered levels of biophysical stimulation.
authors.affiliation: Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland.
authors.forename: Tariq
authors.initials: T
authors.lastname: Mesallati
authors.forename: Conor T
authors.initials: CT
authors.lastname: Buckley
authors.forename: Thomas
authors.initials: T
authors.lastname: Nagel
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Kelly
mesh_terms: D000423:Alcian Blue / Q000378:metabolism; D000818:Animals; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D019245:Compressive Strength / Q000187:drug effects; D004548:Elasticity / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects; D006025:Glycosaminoglycans / Q000378:metabolism; D020100:Hydrogels / Q000494:pharmacology; D007150:Immunohistochemistry; D016014:Linear Models; D016062:Porosity / Q000187:drug effects; D012685:Sepharose / Q000737:chemistry; D013314:Stress, Mechanical; D034421:Sus scrofa; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D024043:Collagen Type II; D006025:Glycosaminoglycans; D020100:Hydrogels; D012685:Sepharose; D000423:Alcian Blue