Tailorable cell culture platforms from enzymatically cross-linked multifunctional poly(ethylene glycol)-based hydrogels

Donna J. Menzies, Andrew Ross Cameron, Trent P Munro, Ernst Wolvetang, Lisbeth Grøndahl, Justin J. Cooper-White

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45 Citations (Scopus)

Abstract

As stem-cell-based therapies rapidly advance toward clinical applications, there is a need for cheap, easily manufactured, injectable gels that can be tailored to carry stem cells and impart function to such cells. Herein we describe a process for making hydrogels composed of hydroxyphenyl propionic acid (HPA) conjugated, branched poly(ethylene glycol) (PEG) via an enzyme mediated, oxidative cross-linking method. Functionalization of the branched PEG with HPA at varying degrees of substitution was confirmed via attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and 1H NMR. The versatility of this hydrogel system was exemplified through variations in the degree of HPA substitution, polymer concentration, and the concentration of cross-linking reagents (horseradish peroxidase and H2O 2), which resulted in a range of mechanical properties and gelation kinetics for these gels. Cross-linking of the PEG-HPA conjugate with a recombinantly produced Fibronectin fragment (Type III domains 7-10) encouraged attachment and spreading of human mesenchymal stem cells (hMSCs) when assessed in both two-dimensional and three-dimensional formats. Interestingly, when encapsulated in both nonfunctionalized and functionalized cross-linked PEG-HPA gels, MSCs showed good viability over all time periods assessed. With tunable gelation kinetics and mechanical properties, these hydrogels provide a flexible in vitro cell culture platform that will likely have significant utility in tissue engineering as an injectable delivery platform for cells to sites of tissue damage.

Original languageEnglish
Pages (from-to)413-423
Number of pages11
JournalBiomacromolecules
Volume14
Issue number2
DOIs
Publication statusPublished - 11 Feb 2013
Externally publishedYes

Cite this

Menzies, D. J., Cameron, A. R., Munro, T. P., Wolvetang, E., Grøndahl, L., & Cooper-White, J. J. (2013). Tailorable cell culture platforms from enzymatically cross-linked multifunctional poly(ethylene glycol)-based hydrogels. Biomacromolecules, 14(2), 413-423. https://doi.org/10.1021/bm301652q