Poly(ethylene glycol)-based Biomaterials in Tissue Engineering, by D. Ezra Aurian-Blajeni

Poly(ethylene glycol) based biomaterials in tissue engineering

Basic structure and use in hydrogels

Poly(ethylene glycol) (PEG), also known as poly(ethylene oxide) and poly(oxyethylene), is a synthetic, non-biodegradable polymer that is widely used as an artificial scaffold in tissue engineering research. PEG chains of any length can be easily synthesized by the controlled polymerization of ethylene oxide or ethylene glycol in aqueous solution. PEG is highly biocompatible and well-suited for use in hydrogels for biological studies. Its repeating alkane-ether motif makes PEG not only very hydrophilic, but also biologically inert at physiological conditions. PEG is also non-immunogenic and resistant to protein adsorption, making it suitable for in vivo as well as in vitro studies. However, unlike natural polymers that are used in hydrogels, PEG is not biodegradable. As a result, PEG is almost always incorporated in block copolymers with biodegradable polymers, such as poly(glycolic acid) (PGA) and poly(lactic acid) (PLA).

Synthetic versatility and controllability

Basic structures and common functionalizations of PEG [ref]

The main advantages of PEG-based hydrogels lie in its chemistry. For one, all chain lengths of PEG are soluble in water and can be synthesized with low polydispersity. PEG has both a linear structure and a branched (star) structure. Its hydroxyl end groups can be readily replaced with a wide variety of functional groups (fig 1). Those end groups can be identical or they can be two different functional groups: this makes PEG extremely versatile, not only in terms of hydrogel architecture, but also in biomolecule conjugation. PEG chains can be biofunctionalized in four important and distinct ways: 1.) incorporation of large, specific biomolecules, such as antibodies(f) or extracellular matrix mimicking sequences like collagen’s characteristic proline-hydroxyproline-glycine repeat(g), 2.) growth factors like VEGF (h), 3) short cell-adhesive sequences, like fibronectin’s RGD (i),

In addition to its chemical composition, the mechanical properties of a PEG-based hydrogel can be also be tuned: stiffness and porosity, which are important physical cues for stem cells, are almost completely determined by the degree of crosslinking among polymer chains. Crosslinking can be achieved through specific chemical reactions, such as Michael-type addition and Click chemistry. It can also be achieved through the use of radiation, like gamma radiation. However, the most prominent method of crosslinking is a free radical mechanism: photopolymerization of PEG acrylates. Photopolymerization of PEG acrylates is what really exploded the use of PEG hydrogels in tissue engineering research. By using light, a liquid solution of PEG acrylates can be converted into a flexible hydrogel in a relatively short time. The pattern, location(s), and exposure times of the applied light can be widely varied: this controllability makes it relatively easy to fabricate 3-D hydrogels that can closely mimic the physical aspects of human tissue. In addition, this can be done at temperature and pH conditions that are found in the human body. Liquid PEG acrylate solutions can

motivation section

the ultimate goal of tissue engineering is to create an implantable material for use in a personalized application of regenerative medicine.

peg-based materials have been used in drug delivery for a long time. for example, there’s an fda approved drug to release progesterone or something. Currently, no fda-approved stem-cell-based therapies.

However, they have proven very useful in studying mechanisms of diseases like cancer and also differentiation of stem cells.

history,

1993- first paper on PEG acrylates

First paper on biofunctionalized PEG hydrogel

First stemcell study

First cancer study

3-d printing

references

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(f) Cheung CY, Anseth KS (2006). Synthesis of immunoisolation barriers that provide localized immunosuppression for encapsulated pancreatic islets. Bioconjug Chem, 17, 1036–1042.

(g) Lee HJ, Lee JS, Chansakul T, Yu C, Elisseef JH, Yu SM (2006). Collagen mimetic peptide-conjugated photopolymerizable PEG hydrogel. Biomaterials 27:5268–5276.

(h) Seliktar D, Zisch AH, Lutolf MP, Wrana JL, Hubbell JA. MMP-2 sensitive, VEGF-bearing bioactive hydrogels for promotion of vascular healing. J Biomed Mater Res A 2004;68:704–716.

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