Biomedical Engineering Reference
In-Depth Information
applications, including biomedical separations, and bio-
medical and pharmaceutical devices.
In these equations, y is the specific volume of the
polymer (i.e., the r
eci
procal of the amorphous density of
the polymer), and
M
n
is the initial molecular weight of
the un-cross-linked polymer.
Intelligent or smart hydrogels
Hydrogels may exhibit swelling behavior dependent on
the external environment. Over the past 30 years there
has been a significant interest in the development and
analysis of environmentally or physiologically responsive
hydrogels (
Peppas, 1991
). Environmentally responsive
materials show drastic changes in their swelling ratio due
to changes in their external pH, temperature, ionic
strength, nature and composition of the swelling agent,
enzymatic or chemical reaction, and electrical or mag-
netic stimuli (
Peppas, 1993
). In most responsive net-
works, a critical point exists at which this transition
occurs.
An interesting characteristic of numerous responsive
gels is that the mechanism causing the network structural
changes can be entirely reversible in nature. The ability of
pH- or temperature-responsive gels to exhibit rapid
changes in their swelling behavior and pore structure in
response to changes in environmental conditions lend
these materials favorable characteristics as carriers for
bioactive agents, including peptides and proteins. This
type of behavior may allow these materials to serve as
self-regulated, pulsatile drug delivery systems.
Properties of important biomedical
hydrogels
The multitude of hydrogels available leaves numerous
choices for polymeric formulations. The best approach
for developing a hydrogel with the desired characteristics
for biomedical application is to correlate the macromo-
lecular structures of the polymers available with the
swelling and mechanical characteristics desired (Peppas
et al.,
2000;
Peppas, 2001
).
The most widely used hydrogel is water-swollen,
cross-linked PHEMA, which was introduced as a bi-
ological material by
Wichterle and Lim (1960)
. The
hydrogel is inert to normal biological processes, shows
resistance to degradation, is permeable to metabolites, is
not absorbed by the body, is biocompatible, withstands
heat sterilization without damage, and can be prepared in
a variety of shapes and forms.
The swelling, mechanical, diffusional, and biomedical
characteristics of PHEMA gels have been studied ex-
tensively. The properties of these hydrogels are de-
pendent upon their method of preparation, polymer
volume fraction, degree of cross-linking, temperature,
and swelling agent.
Other hydrogels of biomedical interest include poly-
acrylamides.
Tanaka (1979)
has done extensive studies
on the abrupt swelling and deswelling of partially hy-
drolyzed acrylamide gels with changes in swelling agent
composition, curing time, degree of cross-linking, degree
of hydrolysis, and temperature. These studies have
shown that the ionic groups produced in an acrylamide
gel upon hydrolysis give the gel a structure that shows
a discrete transition in equilibrium-swollen volume with
environmental changes.
Discontinuous swelling in partially hydrolyzed poly-
acrylamide gels has been studied by
Gehrke
et al.
(1986)
.
Besides HEMA and acrylamides,
N
-vinyl-2-pyrrolidone
(NVP), methacrylic acid (MAA), methyl methacrylate
(MMA), and maleic anhydride (MAH) have all been
proven useful as monomers for hydrogels in biomedical
applications. For instance, cross-linked PNVP is used in
soft contact lenses. Small amounts of MAA as a co-
monomer have been shown to dramatically increase
the swelling of PHEMA polymers. Owing to the hydro-
phobic nature of MMA, copolymers of MMA and HEMA
have a lower degree of swelling than pure PHEMA
(
Brannon-Peppas and Peppas, 1991
). All of these
materials have potential use in advanced technology
pH-Sensitive hydrogels
One of the most widely studied types of physiologically
responsive hydrogels is pH-responsive hydrogels. These
hydrogels are swollen ionic networks containing either
acidic or basic pendant groups. In aqueous media of ap-
propriate pH and ionic strength, the pendant groups can
ionize developing fixed charges on the gel. All ionic ma-
terials exhibit a pH and ionic strength sensitivity. The
swelling forces developed in these systems are increased
over those of nonionic materials. This increase in swelling
force is due to the localization of fixed charges on the
pendant groups. As a result, the mesh size of the poly-
meric networks can change significantly with small pH
changes.
Temperature sensitive hydrogels
Another class of environmentally sensitive gels exhibits
temperature-sensitive swelling behavior due to a change
in the polymer/swelling agent compatibility over the
temperature range of interest. Temperature-sensitive
polymers typically exhibit a lower critical solution tem-
perature (LCST), below which the polymer is soluble.
Above this temperature, the polymers are typically hy-
drophobic and do not swell significantly in water (
Kim,
