Poly(2-oxazoline) Hydrogels for Controlled Fibroblast Attachment

Abstract

Currently there is a lack of choice when selecting synthetic materials with the cell-instructive properties demanded by modern biomaterials. The purpose of this study was to investigate the attachment of cells onto hydrogels prepared from poly(2-oxazoline)s selectively functionalized with cell adhesion motifs. A water-soluble macromer based on the microwave-assisted cationic ring-opening polymerization of 2-methyl-2-oxazoline and 2-(dec-9-enyl)-2-oxazoline was functionalized with the peptide CRGDSG or controls using thiol-ene photochemistry followed by facile cross-linking in the presence of a dithiol cross-linker. The growth of human fibroblasts on the hydrogel surfaces was dictated by the structure and amount of incorporated peptide. Controls without any peptide showed resistance to cellular attachment. The benignity of the cross-linking conditions was demonstrated by the incorporation of fibroblasts within the hydrogels to produce three-dimensional cell-polymer constructs.

RGD-Functionalization of Poly(2-oxazoline)-Based Networks for Enhanced Adhesion to Cancer Cells

“…Like other synthetic or natural polymers, poly(2-oxazoline)s have been functionalized with peptide structures in order to enhance cell adhesion, concomitant with increased biocompatibility and cell-specific drug delivery characteristics. However, reports on that specific topic are rather scarce [9]. The functionalization of polymers with peptide units of arginine-glycine-aspartic acid (RGD) has been under extensive research in recent years [10][11][12][13][14], and combinations of polymer-based materials with constrained pentacyclic peptides, like c(RGDfC) [15,16], have been reported [10,17].…”

“…In particular, the α v β 5 -integrin and its α v β 3 congener have been reported to show strong interaction with the cyclic RGD motif [18,19]. Due to the known overexpression, as well as the high activity of integrins in tumor cells [20,21], research started to focus on the preparation of RGD-functionalized hydrogels for enhanced cancer imaging and for the development of targeted strategies for cancer treatment [9,22]. Nonetheless, the investigation of these phenomena is still in its infancy.…”

Poly(2-oxazoline) hydrogels as next generation three-dimensional cell supports

“…18 Now, we have recently demonstrated a method to synthesize PAOx-based hydrogels using mild aqueous curing conditions, with the ability to include short peptides covalently bound to the polymer, that overcomes this limitation. 19 The approach uses a simple aqueous solution of precursor materials consisting of a water soluble PAOx copolymer with methyl, (which is more watersoluble than the ethyl used previously) and 9-decenyl side chains (pendant alkene groups), a dithiol crosslinker (in this study we used dithiothreitol), thiol-containing peptides (exploiting the thiol in the cysteine residue), and a low percentage of a radical photoinitiator. The solution is then exposed to low flux 365 nm light for several minutes to cure the polymer solution (schematically shown in Fig.…”

Biocompatibility of poly(2-alkyl-2-oxazoline) brush surfaces for adherent lung cell lines

“…Several biological applications have already been studied involving these polymers [15], including drug delivery using micelles [16] or conjugation to a drug or protein [17]. Co-polymers have been investigated for the creation of antimicrobial surfaces [18], to block protein and cell adhesion for coating implant surfaces [19][20] and as a hydrogel for tissue engineering [21].…”