Biomedical Engineering Reference
In-Depth Information
1 Introduction
Hydrogels are hydrophilic macromolecular networks swollen in water or biologi-
cal fluids [
1
]. Wichterle and Lim [
2
] reported the pioneering work using hydro-
philic 2-hydroxyethyl methacrylate (HEMA) hydrogels in 1960. Recently, in situ
gelling systems based on various natural and synthetic polymers have been widely
investigated for biomedical applications due to effective encapsulation of cells
and bioactive molecules, minimally invasive injection, and easy formation in any
desired shape of defects, in addition to several advantages of typical hydrogels
including high water contents similar to extracellular matrix (ECM), controllable
physicochemical properties, and efficient mass transfer [
3
-
5
]. When hydrogels
are prepared by covalent-crosslinking, they form permanent or chemical gels. On
the other hand, when physical intermolecular association induces hydrogels, the
hydrogels form physical gels and their formations are usually reversible.
2 Chemical Hydrogels
Chemical hydrogels are 3D crosslinked networks that formed by new covalent
bonds between water-soluble macromers. To use chemical hydrogels for bio-
medical application, chemical reactions should not damage incorporated biop-
harmaceuticals or cells. There are several chemical crosslinking methods such as
redox-initiated polymerization, photopolymerization, classical organic reactions
between functional groups, and enzymatic reactions.
Redox-initiated polymerization using ammonium persulfate (APS)/N,N,N′,N′-
tetramethylethylenediamine (TEMED) or APS/ascorbic acid has been used to
encapsulate cells in poly(ethylene glycol) (PEG), oligo(PEG fumarate) (OPF),
poly (lactide-co-ethylene oxide-co-fumarate) (PLEOF), chitosan derivatives, or
carboxybetaine hydrogels [
6
-
11
]. In these systems, an increase of initiator concen-
tration led a decrease in the gelling time, however, it also affected the cell viability.
Therefore, low cytotoxic free radical polymerization is needed to use this method
for biomedical applications.
Photo polymerization of vinyl groups bearing polymers via ultraviolet (UV) or
visible light irradiation with photoinitiators is one of most common and effective
encapsulation methods for cell or bioactive molecules in biomedical applications.
The hydrogel can be performed at physiological pH and temperature. Various
photo initiators, such as 2-hydroxy-1-[4-(hydroxyethoxy)phenyl]-2-methyl 1-pro-
panone (Irgacure 2959) [
12
-
14
], lithium acyl phosphinate (LAP) [
15
,
16
], methyl
benzoylformate (MBF) [
17
], or 2,2-dimethoxy-2-phenylacetophenone (DMPA)
[
18
] have been used to produce UV sensitive hydrogels. UV-initiated free radical
polymerization systems showed lower cytotoxicity then redox-initiated polym-
erization. However, UV-irradiation can damage cells, proteins, or tissues; there-
fore, visible light inducible hydrogel systems have been developed. Exposure to
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