title: Integrating valve-inspired design features into poly(ethylene glycol) hydrogel scaffolds for heart valve tissue engineering.
abstract: The development of advanced scaffolds that recapitulate the anisotropic mechanical behavior and biological functions of the extracellular matrix in leaflets would be transformative for heart valve tissue engineering. In this study, anisotropic mechanical properties were established in poly(ethylene glycol) (PEG) hydrogels by crosslinking stripes of 3.4 kDa PEG diacrylate (PEGDA) within 20 kDa PEGDA base hydrogels using a photolithographic patterning method. Varying the stripe width and spacing resulted in a tensile elastic modulus parallel to the stripes that was 4.1-6.8 times greater than that in the perpendicular direction, comparable to the degree of anisotropy between the circumferential and radial orientations in native valve leaflets. Biomimetic PEG-peptide hydrogels were prepared by tethering the cell-adhesive peptide RGDS and incorporating the collagenase-degradable peptide PQ (GGGPQG↓IWGQGK) into the polymer network. The specific amounts of RGDS and PEG-PQ within the resulting hydrogels influenced the elongation, de novo extracellular matrix deposition and hydrogel degradation behavior of encapsulated valvular interstitial cells (VICs). In addition, the morphology and activation of VICs grown atop PEG hydrogels could be modulated by controlling the concentration or micro-patterning profile of PEG-RGDS. These results are promising for the fabrication of PEG-based hydrogels using anatomically and biologically inspired scaffold design features for heart valve tissue engineering.
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX, USA.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX, USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Puperi
authors.affiliation: Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA.
authors.forename: Aline L
authors.initials: AL
authors.lastname: Yonezawa
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX, USA.
authors.forename: Hubert
authors.initials: H
authors.lastname: Tseng
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC, USA.
authors.forename: Maude L
authors.initials: ML
authors.lastname: Cuchiara
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: West
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX, USA. Electronic address: grande@rice.edu.
authors.forename: K Jane
authors.initials: KJ
authors.lastname: Grande-Allen
mesh_terms: D000818:Animals; D016880:Anisotropy; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D055119:Elastic Modulus / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D006350:Heart Valve Prosthesis; D006351:Heart Valves / Q000166:cytology*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D010455:Peptides / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011474:Prosthesis Design; D034421:Sus scrofa; D013718:Tensile Strength / Q000187:drug effects; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D010455:Peptides; C437167:poly(ethylene glycol)diacrylate; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols
keywords: Anisotropy; Bioactivity; Heart valve tissue engineering; Hydrogel; Poly(ethylene glycol)