title: Interpenetrating networks based on gelatin methacrylamide and PEG formed using concurrent thiol click chemistries for hydrogel tissue engineering scaffolds.
abstract: The integration of biological extracellular matrix (ECM) components and synthetic materials is a promising pathway to fabricate the next generation of hydrogel-based tissue scaffolds that more accurately emulate the microscale heterogeneity of natural ECM. We report the development of a bio/synthetic interpenetrating network (BioSINx), containing gelatin methacrylamide (GelMA) polymerized within a poly(ethylene glycol) (PEG) framework to form a mechanically robust network capable of supporting both internal cell encapsulation and surface cell adherence. The covalently crosslinked PEG network was formed by thiol-yne coupling, while the bioactive GelMA was integrated using a concurrent thiol-ene coupling reaction. The physical properties (i.e. swelling, modulus) of BioSINx were compared to both PEG networks with physically-incorporated gelatin (BioSINP) and homogenous hydrogels. BioSINx displayed superior physical properties and significantly lower gelatin dissolution. These benefits led to enhanced cytocompatibility for both cell adhesion and encapsulation; furthermore, the increased physical strength provided for the generation of a micro-engineered tissue scaffold. Endothelial cells showed extensive cytoplasmic spreading and the formation of cellular adhesion sites when cultured onto BioSINx; moreover, both encapsulated and adherent cells showed sustained viability and proliferation.
authors: National Academy of Sciences, National Research Council Postdoctoral Associate, Center for Bio/Molecular Science and Engineering, Naval Research Laboratory, 4555 Overlook Ave, SW Washington, DC 20375, USA. Electronic address: michael.daniele.ctr@nrl.navy.mil.
authors: Michael A
authors: MA
authors: Daniele
authors: Center for Bio/Molecular Science and Engineering, Naval Research Laboratory, 4555 Overlook Ave, SW Washington, DC 20375, USA.
authors: André A
authors: AA
authors: Adams
authors: Center for Bio/Molecular Science and Engineering, Naval Research Laboratory, 4555 Overlook Ave, SW Washington, DC 20375, USA.
authors: Jawad
authors: J
authors: Naciri
authors: Center for Bio/Molecular Science and Engineering, Naval Research Laboratory, 4555 Overlook Ave, SW Washington, DC 20375, USA.
authors: Stella H
authors: SH
authors: North
authors: Center for Bio/Molecular Science and Engineering, Naval Research Laboratory, 4555 Overlook Ave, SW Washington, DC 20375, USA.
authors: Frances S
authors: FS
authors: Ligler
mesh_terms: D000178:Acrylamides / Q000737:chemistry; D057930:Click Chemistry; D005109:Extracellular Matrix / Q000737:chemistry; D005780:Gelatin / Q000737:chemistry*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D000178:Acrylamides; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; D005780:Gelatin; C045985:methacrylamide
keywords: Click chemistry; Extracellular matrix; Gelatin; Interpenetrating network (IPN); Poly(ethylene glycol); Thiol-yne