title: Thermoreversible and Injectable ABC Polypeptoid Hydrogels: Controlling the Hydrogel Properties through Molecular Design.
abstract: A series of ABC triblock copolypeptoids [i.e., poly(N-allyl glycine)-b-poly(N-methyl glycine)-b-poly(N-decyl glycine) (AMD)] with well-defined structure and varying composition have been synthesized by sequential primary amine-initiated ring-opening polymerization of the corresponding N-substitutedN-carboxyanhydride monomers (Al-NCA, Me-NCA, and De-NCA). The ABC block copolypeptoids undergo sol-to-gel transitions with increasing temperature in water and biological media at low concentrations (2.5-10 wt %). The sol-gel transition is rapid and fully reversible with a narrow transition window, evidenced by the rheological measurements. The gelation temperature (Tgel) and mechanical stiffness of the hydrogels are highly tunable:Tgelin the 26.2-60.0 °C range, the storage modulus (G') and Young's modulus (E) in the 0.2-780 Pa and 0.5-2346 Pa range, respectively, at the physiological temperature (37 °C) can be readily accessed by controlling the block copolypeptoid composition and the polymer solution concentration. The hydrogel is injectable through a 24 gauge syringe needle and maintains their shape upon in contact with surfaces or water baths that are kept above the sol-gel transition temperature. The hydrogels exhibit minimal cytotoxicity toward human adipose derived stem cells (hASCs), evidenced from both alamarBlue and PicoGreen assays. Furthermore, quantitative PCR analysis revealed significant up-regulation of theCol2a1gene and down-regulation ofANGPT1gene, suggesting that the hydrogel exhibit biological activity in inducing chondrogenesis of hASCs. It was also demonstrated that the hydrogel can be used to quantitatively encapsulate water-soluble enzymes (e.g., horseradish peroxidase) by manipulating the sol-gel transition. The enzymatic activity of HRP remain unperturbed after encapsulation at 37 °C for up to 7 d, suggesting that the hydrogel does not adversely affect the enzyme structure and thereby the enzymatic activity. These results suggest that the polypeptoid hydrogel a promising synthetic platform for tissue engineering or protein storage applications.
authors.affiliation: Department of Chemistry and Macromolecular Studies Group, Louisiana State University, Baton Rouge, Louisiana 70803, United States.
authors.forename: Sunting
authors.initials: S
authors.lastname: Xuan
authors.affiliation: Department of Chemistry and Macromolecular Studies Group, Louisiana State University, Baton Rouge, Louisiana 70803, United States.
authors.forename: Chang-Uk
authors.initials: CU
authors.lastname: Lee
authors.affiliation: Department of Biological and Agricultural Engineering, Louisiana State University, Baton Rouge, Louisiana 70803, United States.
authors.forename: Cong
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Biological and Agricultural Engineering, Louisiana State University, Baton Rouge, Louisiana 70803, United States.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Doyle
authors.affiliation: Department of Chemical and Biomolecular Engineering, Tulane University, New Orleans, Louisiana 70118, United States.
authors.forename: Yueheng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Macromolecular Studies Group, Louisiana State University, Baton Rouge, Louisiana 70803, United States.
authors.forename: Li
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Chemical and Biomolecular Engineering, Tulane University, New Orleans, Louisiana 70118, United States.
authors.forename: Vijay T
authors.initials: VT
authors.lastname: John
authors.affiliation: Department of Biological and Agricultural Engineering, Louisiana State University, Baton Rouge, Louisiana 70803, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hayes
authors.affiliation: Department of Chemistry and Macromolecular Studies Group, Louisiana State University, Baton Rouge, Louisiana 70803, United States.
authors.forename: Donghui
authors.initials: D
authors.lastname: Zhang