Multi-functional PEGs – new materials for the Life Sciences

PEG – a biocompatible all-round talent

Polyethylene glycol, PEG, is non-toxic, not immunogenic, hydrophilic and highly elastic. Due to these qualities the polymer is a much sought after ingredient in medical products, pharmaceuticals, the chemical and cosmetic industries as well as in tissue engineering. Its application normally requires that PEG be linked to a matrix or cross-linked. This process involves adjusting the cross-link density by means of the chain length of PEG since the functional groups are located at the end of the chain. Such end-group functionalized PEG is commercially available; however, the choice of chain lengths is extremely limited.

Multi-functional PEGs via side chain functionalization

Chemical structure of multi-functional PEGs.

To bypass these limitations, we at the Fraunhofer IGB, in cooperation with the Institute for Interfacial Engineering IGVT at the University of Stuttgart, have developed polymer-analogous and monomer-based synthesis strategies for novel multifunctional PEGs in which the chemically reactive functional groups are found in side chains of PEG. The following are examples of possible reactive functions:

  • thiol
  • amine (primary, secondary)
  • carboxyl
  • photoactive groups

The amount of side groups and, accordingly, the distance between two functional side groups can be adjusted. It is also possible to produce copolymers with the respective functionalized PEGs.

An example: thiol-PEG

Biocompatible hydrogels made of multi-functional PEG materials, developed at Fraunhofer IGB.

Biocompatible hydrogels made of multi-functional PEG materials.

In the past years the thiol-En-Michael-addition has established itself in the field of tissue engineering as a biocompatible
reaction without by-products for the development of cross-linked hydrogel matrix materials. At the Fraunhofer IGB a
novel PEG derivative was synthesized which carries this biocompatible thiol group on each repeating unit. This multi-functional thiol-PEG for which a patent application has been filed is now available for use in the life sciences [1]. Together with Michael acceptors such as PEG-700-bisacrylate hydrogels form within seconds.

In contrast to conventional systems that are based on end-functionalized PEG systems, the qualities of these materials can be precisely adjusted, simply by altering reagent ratios. This is demonstrated with regard to swelling capacities, for instance, which we were able to precisely adapt within a wide range of 10 to 60 percent while constantly maintaining high gel yields (figure to the right).

Biofunctionality

Human fibroblasts on multi-functional PEG hydrogels.

Initial studies, in which modified PEG-based hydrogels were seeded with human fibroblasts, indicate good biocompatibility. Unlike non-functionalized PEG our new hydrogels also appear to be biofunctional. Images taken under the light microscope reveal a high number of adherent cells on the hydrogel after a colonization time of 48 hours.

Outlook

Application example: PEGylation of gold particles to improve biocompatibility.

By means of controlled variations in the reaction process any number of thiol groups can be attached to PEG, providing a wide spectrum of multi-functional PEGs for the construction of hydrogels. Other areas of application, especially of thiol-PEG, are the PEGylation of gold surfaces or of acrylic group-carrying surfaces. A further possible use could consist of using multi-functional PEGs as a biocompatible matrix in drug-delivery systems with custom-made qualities.

Literature

[1] Southan, A.; Schuh, C.; Tovar, G.; Hirth, T., Seitenketten-funktionalisiertes PEG, Patentanmeldung DE 10 2011 114 167.0

Funding

We would like to thank the Peter and Traudl Engelhorn Foundation for funding this research with a post-doc scholarship and the Ministry of Science, Research and the Arts Baden-Württemberg for funding the project “SynElast – desmosin mimetics for the development of a synthetic elastin replacement”, promotional reference 720.830-5-10a.

Project partner

Institute for Interfacial Engineering IGVT, University of Stuttgart