TY - JOUR
T1 - Assessing monocyte phenotype in poly(γ-glutamic acid) hydrogels formed by orthogonal thiol-norbornene chemistry
AU - Kim, Min Hee
AU - Lin, Chien Chi
N1 - Publisher Copyright:
© 2021 IOP Publishing Ltd.
PY - 2021/7
Y1 - 2021/7
N2 - Hydrogels with tunable properties are highly desirable in tissue engineering applications as they can serve as artificial extracellular matrix to control cellular fate processes, including adhesion, migration, differentiation, and other phenotypic changes via matrix induced mechanotransduction. Poly(γ-glutamic acid) (PGA) is an natural anionic polypeptide that has excellent biocompatibility, biodegradability, and water solubility. Moreover, the abundant carboxylic acids on PGA can be readily modified to introduce additional functionality or facilitate chemical crosslinking. PGA and its derivatives have been widely used in tissue engineering applications. However, no prior work has explored orthogonal crosslinking of PGA hydrogels by thiol-norbornene (NB) chemistry. In this study, we report the synthesis and orthogonal crosslinking of PGA-norbornene (PGANB) hydrogels. PGANB was synthesized by standard carbodiimide chemistry and crosslinked into hydrogels via either photopolymerization or enzymatic reaction. Moduli of PGA hydrogels were readily tuned by controlling thiol-NB crosslinking conditions or stoichiometric ratio of functional groups. Orthogonally crosslinked PGA hydrogels were used to evaluate the influence of mechanical cues of hydrogel substrate on the phenotype of naïve human monocytes and M0 macrophages in 3D culture.
AB - Hydrogels with tunable properties are highly desirable in tissue engineering applications as they can serve as artificial extracellular matrix to control cellular fate processes, including adhesion, migration, differentiation, and other phenotypic changes via matrix induced mechanotransduction. Poly(γ-glutamic acid) (PGA) is an natural anionic polypeptide that has excellent biocompatibility, biodegradability, and water solubility. Moreover, the abundant carboxylic acids on PGA can be readily modified to introduce additional functionality or facilitate chemical crosslinking. PGA and its derivatives have been widely used in tissue engineering applications. However, no prior work has explored orthogonal crosslinking of PGA hydrogels by thiol-norbornene (NB) chemistry. In this study, we report the synthesis and orthogonal crosslinking of PGA-norbornene (PGANB) hydrogels. PGANB was synthesized by standard carbodiimide chemistry and crosslinked into hydrogels via either photopolymerization or enzymatic reaction. Moduli of PGA hydrogels were readily tuned by controlling thiol-NB crosslinking conditions or stoichiometric ratio of functional groups. Orthogonally crosslinked PGA hydrogels were used to evaluate the influence of mechanical cues of hydrogel substrate on the phenotype of naïve human monocytes and M0 macrophages in 3D culture.
KW - 3D encapsulation
KW - hydrogel
KW - poly(γ-glutamic acid) (γ-PGA)
KW - thiol-norbornene click chemistry
UR - http://www.scopus.com/inward/record.url?scp=85107084576&partnerID=8YFLogxK
U2 - 10.1088/1748-605X/ac01b0
DO - 10.1088/1748-605X/ac01b0
M3 - Article
C2 - 34037542
AN - SCOPUS:85107084576
SN - 1748-6041
VL - 16
JO - Biomedical Materials (Bristol)
JF - Biomedical Materials (Bristol)
IS - 4
M1 - 045027
ER -