The effect of bioactive hydrogels on the secretion of extracellular matrix molecules by valvular interstitial cells.
Valvular interstitial cells (VICs) were encapsulated in enzymatically degradable, crosslinked hydrogels formed from hyaluronic acid (HA) and poly(ethylene glycol) (PEG) macromolecular monomers. Titration of PEG with HA allowed for the synthesis of gels with a broad compositional spectrum, leading to a range of degradation behavior upon exposure to bovine testes hyaluronidase. The rate of mass loss and release of HA fragments from the copolymer gels depended on the PEG content of the network. These hydrogels were shown to have the dual function of permitting the diffusion of ECM elaborated by 3D cultured VICs and promoting the development of a specific matrix composition. Initial cleavage of hydrogel crosslinks, prior to network mass loss, permit the diffusion of collagen, while later stages of degradation promote elastin elaboration and suppress collagen production due to HA fragment release. Exogenous HA delivery through the cell culture media further demonstrated the utility of delivered HA on manipulating the secretory properties of encapsulated VICs.
Shah
Darshita N
DN
Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80309-0424, USA.
Recktenwall-Work
Sarah M
SM
Anseth
Kristi S
KS
D000818:Animals; D002478:Cells, Cultured; D004549:Elastin / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism; D020100:Hydrogels / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects*; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000737:chemistry; D013552:Swine
D020100:Hydrogels; D011092:Polyethylene Glycols; D006820:Hyaluronic Acid; D004549:Elastin