Multifunctional PEG - new materials for the life sciences

Polyethylene glycol (PEG), is non-toxic, non-immunogenic, hydrophilic and highly elastic. Due to these properties, the polymer is used in a wide range of applications in medical technology products, pharmaceuticals, the chemical and cosmetics industry and tissue engineering. The application usually requires a binding or cross-linking of the PEG. The network density has to be adjusted over the chain length of the PEG, because the functional groups are located at the chain ends. Commercially end group functionalized PEGs are available for this purpose, but the choice of available chain lengths is very limited.

To circumvent this limitation, we at 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 present in side chains of the PEG. As reactive functions are for example possible:

• Thiol
  
• Amine (primary, secondary)
  
• Carboxyl
  
• photoactive groups
  
  The proportion of the contained page groups and thus the distance between two functional page groups can be set. It is also possible to produce copolymers with the corresponding functionalized PEGs.
  
  

In recent years, Thiol-En-Michael addition has become established in the field of tissue engineering as a biocompatible reaction without by-products for the construction of cross-linked hydrogel matrix materials. At Fraunhofer IGB a novel PEG derivative was synthesized which carries these biocompatible thiol groups at each repeating unit. A patent application has been filed for this multifunctional thiol PEG which is now available for use in the life sciences [1]. With Michael acceptors such as PEG-700 diacrylate, hydrogels are formed within a few seconds.

In contrast to conventional systems based on end-functionalized PEGs, the properties of these materials can be easily adjusted via the ratio of the reagents. This is exemplified by the swellability, which we specifically adjust over a wide range from 10 percent up to 60 percent at constantly high gel yields (see graph on the left).

Initial investigations in which the hydrogels based on modified PEGs were colonized with human fibroblasts indicate good biocompatibility. In contrast to non-functionalized PEGs, our new hydrogels even seem to be biofunctional. Light microscopic images show a high number of adherent cells on such a hydrogel after 48 hours of colonization.

By specific variations in the reaction control any amount of thiol groups can be attached to PEGs, so that a wide variety of multifunctional PEGs are available for the formation of hydrogels. Another possible application, especially of the thiol PEG, is the "PEGylation" of surfaces made of gold (Fig. 4) or of surfaces carrying acrylic groups. It is also conceivable to use multifunctional PEGs as a biocompatible matrix of drug delivery systems with tailor-made properties.

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

We would like to thank the Peter and Traudl Engelhorn Foundation for funding the work via a post-doctoral scholarship and the Baden-Württemberg Ministry of Science, Research and the Arts for funding the project "SynElast - Desmosin mimetics for the development of a synthetic elastin substitute", grant no. 720.830-5-10a

Institute for Interfacial Engineering, University of Stuttgart