Tailorable Cell Culture Platforms from Enzymatically Cross-Linked Multifunctional Poly(ethylene glycol)-Based Hydrogels

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• 作者：Donna J. Menzies ; Andrew Cameron ; Trent Munro ; Ernst Wolvetang ; Lisbeth Gr酶ndahl ; Justin J. Cooper-White
• 刊名：Biomacromolecules
• 出版年：2013
• 出版时间：February 11, 2013
• 年：2013
• 卷：14
• 期：2
• 页码：413-423
• 全文大小：645K
• 年卷期：v.14,no.2(February 11, 2013)
• ISSN：1526-4602

文摘

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 H₂O₂), which resulted in a range of mechanical properties and gelation kinetics for these gels. Cross-linking of the PEG鈥揌PA conjugate with a recombinantly produced Fibronectin fragment (Type III domains 7鈥?0) 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鈥揌PA 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.