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dc.contributor.authorKhang, Alexen_US
dc.contributor.authorGonzalez Rodriguez, Andreaen_US
dc.contributor.authorSchroeder, Megan E.en_US
dc.contributor.authorSansom, Jacoben_US
dc.contributor.authorLejeune, Emmaen_US
dc.contributor.authorAnseth, Kristi S.en_US
dc.contributor.authorSacks, Michael S.en_US
dc.date.accessioned2020-09-15T20:14:33Z
dc.date.available2020-09-15T20:14:33Z
dc.date.issued2019-09
dc.identifier.citationAlex Khang, Andrea Gonzalez Rodriguez, Megan E Schroeder, Jacob Sansom, Emma Lejeune, Kristi S Anseth, Michael S Sacks. 2019. "Quantifying heart valve interstitial cell contractile state using highly tunable poly(ethylene glycol) hydrogels." Acta Biomaterialia, Volume 96, pp. 354 - 367. https://doi.org/10.1016/j.actbio.2019.07.010
dc.identifier.issn1742-7061
dc.identifier.urihttps://hdl.handle.net/2144/41392
dc.descriptionPublished in final edited form as: Acta Biomater. 2019 September 15; 96: 354–367. doi:10.1016/j.actbio.2019.07.010.en_US
dc.description.abstractValve interstitial cells (VIC) are the primary cell type residing within heart valve tissues. In many valve pathologies, VICs become activated and will subsequently profoundly remodel the valve tissue extracellular matrix (ECM). A primary indicator of VIC activation is the upregulation of a-smooth muscle actin (aSMA) stress fibers, which in turn increase VIC contractility. Thus, contractile state reflects VIC activation and ECM biosynthesis levels. In general, cell contraction studies have largely utilized two-dimensional substrates, which are a vastly different micro mechanical environment than 3D native leaflet tissue. To address this limitation, hydrogels have been a popular choice for studying cells in a three-dimensional environment due to their tunable properties and optical transparency, which allows for direct cell visualization. In the present study, we extended the use of hydrogels to study the active contractile behavior of VICs. Aortic VICs (AVIC) were encapsulated within poly(ethylene glycol) (PEG) hydrogels and were subjected to flexural-deformation tests to assess the state of AVIC contraction. Using a finite element model of the experimental setup, we determined the effective shear modulus l of the constructs. An increase in l resulting from AVIC active contraction was observed. Results further indicated that AVIC contraction had a more pronounced effect on l in softer gels (72 ± 21% increase in l within 2.5 kPa gels) and was dependent upon the availability of adhesion sites (0.5–1 mM CRGDS). The transparency of the gel allowed us to image AVICs directly within the hydrogel, where we observed a time-dependent decrease in volume (time constant s ¼ 3:04 min) when the AVICs were induced into a hypertensive state. Our results indicated that AVIC contraction was regulated by both the intrinsic (unseeded) gel stiffness and the CRGDS peptide concentrations. This finding suggests that AVIC contractile state can be profoundly modulated through their local micro environment using modifiable PEG gels in a 3D micromechanical-emulating environment. Moving forward, this approach has the potential to be used towards delineating normal and diseased VIC biomechanical properties using highly tunable PEG biomaterials.en_US
dc.format.extentp. 354 - 367en_US
dc.languageEnglish
dc.publisherElsevier BVen_US
dc.relation.ispartofActa Biomaterialia
dc.subjectBiomedical engineeringen_US
dc.titleQuantifying heart valve interstitial cell contractile state using highly tunable poly(ethylene glycol) hydrogelsen_US
dc.typeArticleen_US
dc.description.versionAccepted manuscripten_US
dc.identifier.doi10.1016/j.actbio.2019.07.010
pubs.elements-sourcecrossrefen_US
pubs.notesEmbargo: Not knownen_US
pubs.organisational-groupBoston Universityen_US
pubs.organisational-groupBoston University, College of Engineeringen_US
pubs.organisational-groupBoston University, College of Engineering, Department of Mechanical Engineeringen_US
pubs.publication-statusPublisheden_US
dc.identifier.mycv502526


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