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

Abstract

Synthetic hydrogels selectively decorated with cell adhesion motifs are rapidly emerging as promising substrates for 3D cell culture. When cells are grown in 3D they experience potentially more physiologically relevant cell-cell interactions and physical cues compared with traditional 2D cell culture on stiff surfaces. A newly developed polymer based on poly(2-oxazoline)s has been used for the first time to control attachment of fibroblast cells and is discussed here for its potential use in 3D cell culture with particular focus on cancer cells toward the ultimate aim of high-throughput screening of anticancer therapies. Advantages and limitations of using poly(2-oxazoline) hydrogels are discussed and compared with more established polymers, especially polyethylene glycol (PEG).

Poly(2‐oxazoline) Hydrogels: State‐of‐the‐Art and Emerging Applications

“…In the same study, proof‐of‐principle experiments showed that it was possible to encapsulate fibroblasts within photocured hydrogels, although multiple time‐points were not collected. Similarly, a study examining the MCF‐10A epithelial cell line seeded onto PAOx hydrogels with and without RGD peptide showed little cell adhesion without the peptide but good epithelial colony formation on the hydrogels with peptide . An extension of this work with a breast cancer cell line, MDA‐MB‐231, on nondegradable and matrix metalloproteinase (MMP)‐degradable hydrogels showed the spheroid morphology similar to that found in breast cancer could be achieved with the MMP‐degradable sequence used to cross‐link the hydrogels ( Figure 5 ; unpublished data).…”

“…A number of natural and synthetic polymer 3D hydrogels exist each with their own advantages and disadvantages . One advantage of using PAOx for in vitro models is the possibility of adding biological signaling molecules to the side‐groups to promote cell function . One of the first demonstrations show that cell adhesion to PAOx hydrogels can be controlled used the ubiquitous RGD integrin binding minimum peptide sequence.…”

Poly(2‐oxazoline) hydrogels crosslinked with aliphatic bis(2‐oxazoline)s: Properties, cytotoxicity, and cell cultivation

“…45 Up to date, the cultivation studies were limited to the poly(2-oxazoline)s crosslinked by thiol-ene click reaction. In our work, we focused on the hydrogels prepared by the copolymerization of (2-ethyl-2-oxazoline) with bis(2-oxazoline) crosslinkers.…”

Poly(2-isopropenyl-2-oxazoline) Hydrogels for Biomedical Applications

“…[1][2][3][4][5][6] To date, extensive studies have been directed towards the development of synthetic hydrogels for wound dressing, [7][8][9] tissue engineering, 10-13 ophthalmology 14,15 and drug delivery. [16][17][18][19][20] Hydrogels are three-dimensional networks formed from hydrophilic homopolymers, copolymers, or macromers cross-linked to form water-insoluble polymer matrices. 21 The hydrogels prepared via chemical cross-linking from synthetic hydrophilic monomers or polymers are often preferred over natural polymers due to their structural versatility, reproducibility of synthesis, controlled structure and improved mechanical properties.…”

“…The majority of studies on synthetic polymer hydrogels are based on the use of poly(ethylene glycol)s (PEG), 20,24 poly(vinylpyrrolidone) (PVP), [25][26][27] poly(vinyl alcohol) (PVA), [28][29][30] poly(hydroxyethyl methacrylate) (PHEMA), 19,[31][32][33][34] and more recently poly(2-oxazoline)s (PAOx). 18,[35][36][37] Although, these polymers have certain advantages they all come hand in hand with shortcomings that can limit their applicability as biomaterials. PEG has been the most commonly used water-soluble biomaterial for biomedical applications, because of the commercial availability in a wide range of molecular weights together with its hydrophilicity, solubility, biocompatibility, and reduced protein adsorption.…”