Hyaluronan Hydrogels for a Biomimetic Spongiosa Layer of Tissue Engineered Heart Valve Scaffolds.
Advanced tissue engineered heart valves must be constructed from multiple materials to better mimic the heterogeneity found in the native valve. The trilayered structure of aortic valves provides the ability to open and close consistently over a full human lifetime, with each layer performing specific mechanical functions. The middle spongiosa layer consists primarily of proteoglycans and glycosaminoglycans, providing lubrication and dampening functions as the valve leaflet flexes open and closed. In this study, hyaluronan hydrogels were tuned to perform the mechanical functions of the spongiosa layer, provide a biomimetic scaffold in which valve cells were encapsulated in 3D for tissue engineering applications, and gain insight into how valve cells maintain hyaluronan homeostasis within heart valves. Expression of the HAS1 isoform of hyaluronan synthase was significantly higher in hyaluronan hydrogels compared to blank-slate poly(ethylene glycol) diacrylate (PEGDA) hydrogels. Hyaluronidase and matrix metalloproteinase enzyme activity was similar between hyaluronan and PEGDA hydrogels, even though these scaffold materials were each specifically susceptible to degradation by different enzyme types. KIAA1199 was expressed by valve cells and may play a role in the regulation of hyaluronan in heart valves. Cross-linked hyaluronan hydrogels maintained healthy phenotype of valve cells in 3D culture and were tuned to approximate the mechanical properties of the valve spongiosa layer. Therefore, hyaluronan can be used as an appropriate material for the spongiosa layer of a proposed laminate tissue engineered heart valve scaffold.
Department of Bioengineering, Rice University , Houston, Texas 77005, United States.
Daniel S
DS
Puperi
Department of Biomedical Engineering, University of Glasgow , Glasgow, United Kingdom.
Ronan W
RW
O'Connell
Department of Bioengineering, Rice University , Houston, Texas 77005, United States.
Zoe E
ZE
Punske
Department of Biomedical Engineering, Duke University , Durham, North Carolina 27708, United States.
Yan
Y
Wu
Department of Biomedical Engineering, Duke University , Durham, North Carolina 27708, United States.
Jennifer L
JL
West
Department of Bioengineering, Rice University , Houston, Texas 77005, United States.
K Jane
KJ
Grande-Allen
D000818:Animals; D032701:Biomimetics / Q000379:methods*; D002478:Cells, Cultured; D006351:Heart Valves / Q000166:cytology*; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D011509:Proteoglycans; D013552:Swine; D013718:Tensile Strength; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
D020100:Hydrogels; D011509:Proteoglycans; D006820:Hyaluronic Acid