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Synthesis of oligo(poly(ethylene glycol) fumarate)

Nature Protocols volume 7, pages 1219–1227 (2012)Cite this article

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Abstract

This protocol describes the synthesis of oligo(poly(ethylene glycol) fumarate) (OPF; 1–35 kDa; a polymer useful for tissue engineering applications) by a one-pot reaction of poly(ethylene glycol) (PEG) and fumaryl chloride. The procedure involves three parts: dichloromethane and PEG are first dried; the reaction step follows, in which fumaryl chloride and triethylamine are added dropwise to a solution of PEG in dichloromethane; and finally, the product solution is filtered to remove by-product salt, and the OPF product is twice crystallized, washed and dried under vacuum. The reaction is affected by the molecular weight of PEG and reactant molar ratio. The OPF product is cross-linked by radical polymerization by either a thermally induced or ultraviolet-induced radical initiator, and the physical properties of the OPF oligomer and resulting cross-linked hydrogel are easily tailored by varying PEG molecular weight. OPF hydrogels are injectable, they polymerize in situ and they undergo biodegradation by hydrolysis of ester bonds. The expected time required to complete this protocol is 6 d.

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Figure 1
Figure 2
Figure 3: Apparatus for synthesis of OPF: distillation of dichloromethane (used in Steps 5–10).
Figure 4
Figure 5

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Acknowledgements

The work described in this protocol was supported by grants from the US National Institutes of Health (R01 AR48756) and the Armed Forces Institute of Regenerative Medicine (W81XWH-08-2-0032). L.A.K. acknowledges support from a graduate fellowship from the National Science Foundation (0940902).

Author information

Authors and Affiliations

  1. Department of Chemical and Biomolecular Engineering, Rice University, Houston, Texas, USA

    Lucas A Kinard & Antonios G Mikos

  2. Department of Bioengineering, Rice University, Houston, Texas, USA

    F Kurtis Kasper & Antonios G Mikos

Authors
  1. Lucas A Kinard
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  2. F Kurtis Kasper
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  3. Antonios G Mikos
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Contributions

L.A.K., F.K.K. and A.G.M. optimized the procedure. L.A.K. drafted the manuscript. F.K.K. and A.G.M. supervised the project and critically revised the manuscript.

Corresponding author

Correspondence to Antonios G Mikos.

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Competing interests

A.G.M. is inventor on a patent involving the material described in this protocol. The remaining authors declare no competing financial interests.

Supplementary information

Supplementary Figure 1

A typical 1H NMR spectrum (400 MHz, CDCl3, ambient temperature) of OPF3K showing chemical shifts of important peaks. (PDF 86 kb)

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Kinard, L., Kasper, F. & Mikos, A. Synthesis of oligo(poly(ethylene glycol) fumarate). Nat Protoc 7, 1219–1227 (2012). https://doi.org/10.1038/nprot.2012.055

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