Poly(2-alkyl-2-oxazoline)s (PAOx) are enjoying renewed interest thanks to recent advances in their synthesis and potential as biomaterials. Hydrogels are one of the most important types of biomaterials and have a long and successful history in scientific and medical applications. Many early hydrogels were based on passive, inert materials, but more recently, new hydrogels with function and dynamic features have become possible. Despite these advances, there has been little innovation in the backbone polymers used for such hydrogels, and almost all studies rely on just a select few hydrophilic polymers, hindering further advances. The poly(2-oxazoline)s are a promising alternative to more established hydrogel materials, including poly(ethylene glycol) (PEG), and the range of 2-oxazoline monomers available is ever increasing, which has opened up the possibilities for numerous types of crosslinking reactions. Included in these are very mild and cell-compatible conditions allowing for use with cells. The protein-resistant properties of PAOx, coupled with their ease of functionalization make them ideal candidates for the basis for cell-instructive hydrogels for use in 3D cell culture to study disease. We have used copolymers of methyl 2-oxazolines with unsaturated alkyl-2-oxazolines to produce hydrophilic networks decorated with peptides consisting of integrin bindings sites and enzyme-degradable sites via simple thiol-ene photochemistry. Crosslinking was achieved using di-thiol functional small molecules, also exploiting photochemistry giving temporal control over the gelation process. The resulting PAOx hydrogels showed good swelling properties with control over adhesion of human fibroblasts on the surface of the gels. When seeded with breast cancer cells, the hydrogels containing matrix metalloproteinase degradable crosslinks became populated with 3D cancer spheroids with morphology similar to that observed in cancerous tissue. As such, these fully synthetic hydrogels can be used to study cancerous and other diseased tissue types in vitro with improved reproducibility and handling over existing 3D cell culture systems.

Designer hydrogels based on poly(2-oxazoline)s for 3D cell culture systems

248th National Meeting (2014)

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