title: The role of physiological mechanical cues on mesenchymal stem cell differentiation in an airway tract-like dense collagen-silk fibroin construct.
abstract: Airway tracts serve as a conduit of transport in the respiratory system. Architecturally, these are composed of cartilage rings that offer flexibility and prevent collapse during normal breathing. To this end, the successful regeneration of an airway tract requires the presence of differentiated chondrocytes and airway smooth muscle cells. This study investigated the role of physiological dynamic mechanical stimulation, in vitro, on the differentiation of mesenchymal stem cells (MSCs), three-dimensionally seeded within a tubular dense collagen matrix construct-reinforced with rings of electrospun silk fibroin mat (TDC-SFC). In particular, the role of either shear stress supplied by laminar fluid flow or cyclic shear stress in combination with circumferential strain, provided by pulsatile flow, on the chondrogenic differentiation, and contractile lineage of MSCs, and their effects on TDC-SFC morphology and mechanical properties were analysed. Chondrogenic differentiation of MSCs was observed in the presence of chondrogenic supplements under both static and laminar flow cultures. In contrast, physiological pulsatile flow resulted in preferential cellular orientation within TDC-SFC, as dictated by dynamic circumferential strain, and induced MSC contractile phenotype expression. In addition, pulsatile flow decreased MSC-mediated collagen matrix remodelling and increased construct circumferential strength. Therefore, TDC-SFC demonstrated the central role of a matrix in the delivery of mechanical stimuli over chemical factors, by providing an in vitro niche to control MSC differentiation, alignment and its capacity to remodel the matrix.
authors.affiliation: Department of Mining and Materials Engineering, McGill University, Montreal, Quebec, Canada H3A 2B2.
authors.forename: Chiara E
authors.initials: CE
authors.lastname: Ghezzi
authors.affiliation: Department of Mining and Materials Engineering, McGill University, Montreal, Quebec, Canada H3A 2B2.
authors.forename: Benedetto
authors.initials: B
authors.lastname: Marelli
authors.affiliation: Innovhub - Stazioni Sperimentali per l'Industria, Div. Stazione Sperimentale per la Seta, Milan, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Donelli
authors.affiliation: Innovhub - Stazioni Sperimentali per l'Industria, Div. Stazione Sperimentale per la Seta, Milan, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Alessandrino
authors.affiliation: Innovhub - Stazioni Sperimentali per l'Industria, Div. Stazione Sperimentale per la Seta, Milan, Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Freddi
authors.affiliation: Department of Mining and Materials Engineering, McGill University, Montreal, Quebec, Canada H3A 2B2. Electronic address: showan.nazhat@mcgill.ca.
authors.forename: Showan N
authors.initials: SN
authors.lastname: Nazhat
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020219:Chondrogenesis / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology*; D005349:Fibroins / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D008810:Mice, Inbred C57BL; D012137:Respiratory System / Q000166:cytology*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D003094:Collagen; D005349:Fibroins; D020782:Matrix Metalloproteinases
keywords: Airway smooth muscle cells; Cartilage; Dense collagen gel; Silk fibroin; Trachea