生醫材料專題

Lecture time:
Tuesday 15:30-18:20
Classroom: 綜604
 Special Topics on Biomaterials

This class focus on biomedical applications of hydrogels

Goal

In this class, students will understand what hydrogels are, types of

hydrogels, physiochemical and mechanical properties of hydrogels, the
application of hydrogels in tissue engineering and drug release.
Special Topics on Biomaterials

l Textbook
Materials given in the class

l Grading
Midterm exam 40%
Oral presentation of literature 20%
Final report 40%
 What is a hydrogel?
l water + solid material
Ø biphasic
Ø a mixture of porous, permeable solids → water-insoluble 3D
network
Ø at least 10% by weight or volume of interstitial fluid composed
completely or mainly by water
Ø hydrophilic solid material → the inclusion of hydrophilic groups
such as -NH2, -CONH, -SO3H, -CONH2, -COOH, and -OH
Hydrogels are crosslinked 3D networks of hydrophilic polymer chains
and are capable of holding large amounts of water.
 Swelling behavior of hydrogels
l The physical behavior of biomedical hydrogels is dependent on
their dynamic swelling and equilibrium in water and in aqueous
solutions, affecting
Ø the solute diffusion coefficient through these hydrogels
Ø the surface properties and surface molecule mobility
Ø the optical properties, especially in relation to contact lens
applications
Ø the mechanical properties
l The weight degree of swelling, q, which is the ratio of the weight
of the swollen sample over that of the dry sample.
 Classification of hydrogels
l Based on the method of preparation
(1) Homopolymer hydrogels are cross-linked networks of one type of
hydrophilic monomer unit.
(2) Copolymer hydrogels are produced by cross-linking of chains composed
of two comonomer units, at least one of which must be hydrophilic to
render them water swellable.
(3) Multi-polymer hydrogels are produced from three or more comonomers
reacting together.
(4) Interpenetrating polymer network (IPN) hydrogels are comprised of
two or more networks which are at least partially interlaced on a polymer
scale but not covalently bonded to each other. The network cannot be
separated unless chemical bonds are broken.
Formation of an interpenetrating network (IPN) hydrogel

FIGURE I.2.5.4
Classification by source
l poly(hydroxyethyl
methacrylate) (PHEMA)
l polyethylene glycol (PEG)
l polyacrylic acid (PAA)
l poly(vinyl alcohol) (PVA)
l zwitterionic polymers
l Proteins (collagen, gelatin,
silk)
l Polysaccharides (chitosan,
alginate, hyaluronic acid,
cellulose)
 Formation of hydrogels

l Crosslinking of the network hydrophilic chains allows them to retain

water in their structure without being dissolved
l Two types of crosslinking
Ø covalent bonds
Ø non-covalent bonds: ionic force, hydrogen bonds, affinity,
hydrophobic interactions, polymer crystallites.
 methylcellulose

https://doi.org/10.1016/j.biotechadv.2019.03.009
Designed Monomers and Polymers, 2016,
19(5): 456–478
http://dx.doi.org/10.1080/15685551.2016.1169380
 Mechanical properties of hydrogels

1. Elastic: described by a constant elastic modulus, E, and represents the

classical tool for mechanobiology studies in‐vitro;
2. Viscoelastic, time‐dependent behavior: described by one or more
elastic moduli, E, and viscous moduli, ηi, with values that are constant
over time;
3. Dynamic elastic: described by an elastic modulus, E(t), which change
or evolves as a function of time
4. Dynamic viscoelastic, with viscoelastic properties which evolve over
time: described by one or more elastic moduli Ei(t), and viscosities,
ηi(t).

Materials 2020, 13, 438; doi:10.3390/ma13020438

Mechanical properties of hydrogels

Materials 2020, 13, 438; doi:10.3390/ma13020438

Representing hydrogel viscoelasticity with lumped
parameter models Maxwell‐type Standard
Linear Solid (SLS) model

Materials 2020, 13, 438; doi:10.3390/ma13020438

Gelation process

elastic (G′) modulus

loss (G″) modulus

gel point (tc)

the critical crossover value
(G′ = G″ = Gc)

https://doi.org/10.1016/j.polymer.2005.10.129
 Swelling behavior of hydrogels
l An interesting characteristic of numerous stimuli-responsive “smart”
gels is that the mechanism causing the network structural changes
can be entirely reversible in nature.
l 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 lends these materials favorable
characteristics as carriers for delivery of drugs, including peptides
and proteins.
 pH-Sensitive Hydrogels
l These hydrogels are swollen ionic networks containing either acidic or
basic pendant groups.
l In aqueous media of appropriate pH and ionic strength, the pendant groups
can ionize and develop fixed charges on the gel, leading to rapid swelling.
l All ionic hydrogels exhibit both pH and ionic strength sensitivity,
especially around the pK of the pH-sensitive group.
l These gels typically contain ionizable pendant groups such as carboxylic
acids or amine groups.
Ø poly(acrylic acid) (PAA), poly(methacrylic acid) (PMAA),
poly(diethylaminoethyl methacrylate) (PDEAEMA), and
poly(dimethylaminoethyl methacrylate) (PDMAEMA).
 Temperature-responsive hydrogels
l Temperature-sensitive polymers typically exhibit a lower critical
solution temperature (LCST), below which the polymer is soluble.
l Above this temperature, the polymers may lose their hydrophobically-
bound water, and phase separate, causing the gel to collapse.
l Below the LCST, the cross-linked gel re-swells to significantly higher
degrees because of the increased hydrophobic bonding with water.
l Poly(N-isopropyl acrylamide) (PNIPAAm) has been the most widely
studied temperature-responsive polymer and hydrogel, with an LCST
around 32–34°C
 Hydrogels for biomedical applications
l The design should focus on those salient hydrogel features that give
rise to the desired properties most suitable for the biomedical
application
Ø structure integrity: mechanical properties
Ø sustained release: such as transport properties
Ø biocompatibility: such as cytotoxicity, mutagenesis, and/or
carcinogenesis
Ø bioactivity: such as tissue interactions
Ø chemical stability: such as degradability
Hydrogels for biomedical applications
l The hydrophilic character of hydrogels
makes them attractive for a variety of
biomedical and pharmaceutical applications.
Ø high water contents ▶ hydrogels for
delivering drugs from ingested tablets and
osmotic pumps
Ø as contact lenses applied to the eye, or as
drug-releasing coatings on mucosal, skin or
open wound surfaces.
Ø as non-fouling coatings on implants and
devices that may contact blood, such as
catheters.
Ø as scaffolds for tissue engineering implants.
 Structured Hydrogels in
CNS models and therapy

https://doi.org/10.1016/j.biotechadv.2019.03.009
 Hydrogels for biomedical applications

l The hydrophilic character of hydrogels makes them

attractive for a variety of biomedical and
pharmaceutical applications.
Ø Because of their normally high water contents,
hydrogels have been useful for delivering drugs from
ingested tablets and osmotic pumps.
Ø They have been successful as contact lenses applied to
the eye, or as drug-releasing coatings on mucosal, skin
or open wound surfaces.
Different sites in body
where hydrogels can
deliver drug
Specific applications of hydrogels in oral drug delivery
http://dx.doi.org/10.1016/j.eurpolymj.2014.11.024
 Diffusion-controlled drug delivery
(1) Water-insoluble polymer matrix

Time
(2) Reservoir system with water-insoluble polymer matrix

Time
 Environment-stimulated drug delivery
l Respond to environmental change
Ø temperature, pH, electric signal, light
l Reversible volume phase transition or sol-gel phase transition

Change in pH for Drug-loaded gel

gel swelling
Change in temperature
for gel collapse

Drug release
through the Drug release by the
swollen network squeezing action
Tissue engineering