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Designing Visible Light‐Cured Thiol‐Acrylate Hydrogels for Studying the HIPPO Pathway Activation in Hepatocellular Carcinoma Cells
Author(s) -
Lin TsaiYu,
Bragg John C.,
Lin ChienChi
Publication year - 2016
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201500361
Subject(s) - self healing hydrogels , chemistry , acrylate , ethylene glycol , peptide , dithiol , polymer chemistry , peg ratio , biophysics , copolymer , combinatorial chemistry , polymer , biochemistry , organic chemistry , finance , economics , biology
Various polymerization mechanisms have been developed to prepare peptide‐immobilized poly(ethylene glycol) (PEG) hydrogels, a class of biomaterials suitable for studying cell biology in vitro. Here, a visible light mediated thiol‐acrylate photopolymerization scheme is reported to synthesize dually degradable PEG‐peptide hydrogels with controllable crosslinking and degradability. The influence of immobilized monothiol pendant peptide is systematically evaluated on the crosslinking of these hydrogels. Further, methods are proposed to modulate hydrogel crosslinking, including adjusting concentration of comonomer or altering the design of multifunctional peptide crosslinker. Due to the formation of thioether ester bonds, these hydrogels are hydrolytically degradable. If the dithiol peptide linkers used are susceptible to protease cleavage, these thiol‐acrylate hydrogels can be designed to undergo partial proteolysis. The differences between linear and multiarm PEG‐acrylate (i.e., PEGDA vs PEG4A) are also evaluated. Finally, the use of the mixed‐mode thiol‐acrylate PEG4A‐peptide hydrogels is explored for in situ encapsulation of hepatocellular carcinoma cells (Huh7). The effects of matrix stiffness and integrin binding motif (e.g., RGDS) on Huh7 cell growth and HIPPO pathway activation are studied using PEG4A‐peptide hydrogels. This visible light polymerized thiol‐acrylate hydrogel system represents an alternative to existing light‐cured hydrogel platforms and shall be useful in many biomedical applications.