Review
Bioactive modification of poly(ethylene glycol) hydrogels for tissue engineering
Junmin Zhu
*
Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA
article info
Article history:
Received 7 January 2010
Accepted 16 February 2010
Available online 19 March 2010
Keywords:
Poly(ethylene glycol) (PEG)
Hydrogel
Bioactive modification
Tissue engineering
Biomimetic scaffold
Extracellular matrix (ECM)
abstract
In this review, we explore different approaches for introducing bioactivity into poly(ethylene glycol)
(PEG) hydrogels. Hydrogels are excellent scaffolding materials for repairing and regenerating a variety of
tissues because they can provide a highly swollen three-dimensional (3D) environment similar to soft
tissues. Synthetic hydrogels like PEG-based hydrogels have advantages over natural hydrogels, such as
the ability for photopolymerization, adjustable mechanical properties, and easy control of scaffold
architecture and chemical compositions. However, PEG hydrogels alone cannot provide an ideal envi-
ronment to support cell adhesion and tissue formation due to their bio-inert nature. The natural
extracellular matrix (ECM) has been an attractive model for the design and fabrication of bioactive
scaffolds for tissue engineering. ECM-mimetic modification of PEG hydrogels has emerged as an
important strategy to modulate specific cellular responses. To tether ECM-derived bioactive molecules
(BMs) to PEG hydrogels, various strategies have been developed for the incorporation of key ECM bio-
functions, such as specific cell adhesion, proteolytic degradation, and signal molecule-binding. A number
of cell types have been immobilized on bioactive PEG hydrogels to provide fundamental knowledge of
cell/scaffold interactions. This review addresses the recent progress in material designs and fabrication
approaches leading to the development of bioactive hydrogels as tissue engineering scaffolds.
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
Tissue engineering applies methods from engineering and life
sciences to create artificial constructs to direct tissue regeneration
[1]. Hydrogels have been studied intensively and used as tissue
engineering scaffolds, because they can provide a highly swollen
three-dimensional (3D) environment similar to soft tissues and
allow diffusion of nutrients and cellular waste through the elastic
networks [2,3]. They have been used to repair and assist regener-
ation of a variety of tissues, such as cartilage, bone and vasculature
[4e7]. There are two major types of hydrogels, natural and
synthetic hydrogels, according to their origin [3,8,9]. Natural
hydrogels are made mainly from natural polymer-based materials,
such as proteins (e.g., collagen, gelatin, and fibrin), and poly-
saccharides (e.g., alginate chitosan, hyaluronic acid, dextran).
Synthetic hydrogels are made from synthetic polymers, such as
poly(acrylic acid) (PAA), poly(ethylene glycol) (PEG), poly(vinyl
alcohol) (PVA), polyacrylamide (PAAm), and polypeptides.
Natural hydrogels, such as collagen and fibrin, have been used as
scaffolds because they possess many of critical biological functions
like cell adhesion and biodegradation, which are lacking from
synthetic polymers. However, the use of animal derived ECM
proteins as scaffolds is often restricted due to concerns of potential
immunogenic reactions and infection, as well as their relatively
poor mechanical properties [10e12]. Synthetic hydrogels have
emerged as an alternative choice for hydrogel scaffolds. Synthetic
hydrogels have advantages over natural hydrogels, such as the
ability for photopolymerization, adjustable mechanical properties,
and convenient control of scaffold architecture and chemical
compositions [8]. They can be tailored for specific applications with
the incorporation of biofunctions, and their transport properties
can also be customized by adjusting polymer chain lengths and
density [2].
PEG has been an important type of hydrophilic polymers for
biomedical applications, including surface modification, bio-
conjugation, drug delivery and tissue engineering because they
have critical properties, such as good biocompatibility, non-
immunogenity, and resistance to protein adsorption [13,14]. PEG
has linear and branched (multiarm or star) structures (Fig. 1). The
basic PEG structure is PEG diol with two hydroxyl end groups,
which can be converted into other functional groups, such as
methyloxyl, carboxyl, amine, thiol, azide, vinyl sulfone, azide,
acetylene, and acrylate [15]. The two functional end groups can be
the same (symmetric) or different (asymmetric), which are versa-
tile for hydrogel formation or for conjugating with biomolecules.
Three major crosslinking methods have been used to make PEG
*
Tel.: þ1 216 368 0270; fax: þ1 216 368 4969.
E-mail address: junmin.zhu@case.edu
Contents lists available at ScienceDirect
Biomaterials
journal homepage: www.elsevier.com/locate/biomaterials
0142-9612/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.biomaterials.2010.02.044
Biomaterials 31 (2010) 4639e4656