lect 3-4-140320 hydrogels_print
TRANSCRIPT
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MSE 598/494 Bio-inspired Materials and BiomaterialsMSE 598/494 Bio-inspired Materials and Biomaterials
Instructor: Ximin He
TA: Xiying Chen Email: [email protected]
2014-04-20
Lecture 3. Smart Stimuli-Responsive Materials I
Stimuli-responsive Hydrogels
Octopus Camouflage Adaptive
Octopus is matching:
Pattern
Color
Brightness
Texture
of the algae
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Insane in the Chromatophores
Squid (a type of cepholopod) pigment cell (chromatophore) -- Each chromatophore
has tiny muscles along the circumference of the cell that can contract to reveal thepigment underneath.
iPod nano (stimulator) a suction electrode squids fin nerve
3
youtube
How Adept Can We Be?
Brainstorming:
The properties we would like to own
Sense
Tactile
Vision
Actuate
to change
Color
Shape Size/Dimension Sense Actuate
Stimuli Respond
Stimuli-responsive Materials
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Hydrogel
Definition:
Three-dimensional networks composed of crosslinked hydrophilic polymerchains that are able to drastically change their volume and other properties.
- Large water content: typically >90%
- Large volume change
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1. Crosslinking allows them avoid dissolution and swell in 3-D .
2. Hydrophilicity allows absorbing H2O moledules via molecule forces:
Hydrogen bonds:Forming between H and C, N, O, and F
Van de Waals force
The sum of the attractive or repulsive forces between neutral molecules
H2O
super-effective way to hold liquid in baby diapers
Hydrogels: Superabsorbent Polymers
help farmers retain water in their soil in times of drought
food, medicine
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Biological tissue Artificial tissuePorous tissue scaffoldings for tissue
regeneration for cardiac repair
copoly(ether-esters)-polyamides blend hydrogel
(synthetic hydrogel)
Biological tissue scaffold revealed a porous
structure with an apparent interconnectivity
Collagen
hydrogel
(Natural
hydrogel)
10 m 6 m
Bone scaffoldCollagen hydrogel-ceramic composite
(natural-synthetic blend)
1 cm
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Hydrogels: Cell Culture Tissue Scaffold
Stimuli-Responsive Hydrogels
Definition:
Stimuli-responsive hydrogels, or smart hydrogels, are hydrogels that are able tochange their volume and other properties in response to environmental
stimuli such as pH, temperature and certain chemicals.
Functions:
Hydrogels provide a means to rapidly translate:
a variety of environmental stimuli a chemo-mechanical response
via the reversible volume change of the
polymer network
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Stimuli-Responsive Hydrogels
P. Kim, L. Zarzar, X. He, et al. Current Opinion in Solid State & Materials Science (2011)9
Via molecule forces:
Van de Waals force
Hydrogen bond
Types of Responsiveness Mechanisms
Type 1: Charged groups in hydrogel network:
by changes in osmotic pressure
a change in pH induces dissociation of electrolyte groups,followed by charge-induced swelling of hydrogels
Humidity-, pH-, and temperature- responsive hydrogels
Type 2: Enzymatic production of charged groups:
also applicable to the designs of biologically stimuli-responsive
hydrogels that swell or shrink in the presence of a target enzyme
Glucose- and enzyme-responsive hydrogels
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pH-responsive hydrogel
Poly(acrylamide-co -acrylic acid)
p(AAm-co -AAc)
pH
volume
Anionic
hydrogel
pKa
pH < pKa
protonated
reduced solubility,
Contracted state
pH > pKa
deprotonated, ionized
increased solubility
Swollen state
* pKa, acid dissociation const ant:
a quantitative measure of the strength of an acid in solution
reversible
Mechanism:
co-polymer:
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Preparation
Synthesis:
Solution-based polymerization
Cast into any shape
cross-linkermonomer
initiator
or
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bis-AAM = N,N-
methylenebisacrylamide
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Temperature-responsive hydrogel
poly(N
-isopropylacrylamide)(pNIPAAm)
Preparation:
Monomer: NIPAM, commercially available Crosslinker:N,N-methylene-bis-acrylamide (MBAm) orN,N-
cystamine-bis-acrylamide (CBAm)
initiator:
crosslinker:
Temperature-responsive hydrogel
Mechanism:
lower critical solution temperature
phase transition
swollen hydrated state shrunken dehydrated state
1. Lower Critical Solution Temperature (LCST):
the critical temperature below which the components of a mixture are miscible for allcompositions LCST of pNIPAAm = 32 oC, tunable by introducing hydro-philic/phobic molecules
2. Governed by Entropy: a measure of disorder (that is a property of the system's state, and that variesdirectly with any reversible change in heat in the system and inversely with the temperature of the system)
G(p,T) = H TS
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Temperature-responsive hydrogel
Applications:LCST of PNIPAmHuman body temperature
Tissue engineering Controlled drug delivery
adhesion (37C) and detachment (20C) of a endothelial cell
on a poly(N-isopropylacrylamide)-grafted surface
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Glucose-responsive Hydrogels
A potential autonomous treatment of insulin-dependent diabetesmellitus (IDDM), diabetes II.
o Insulin is a hormone secreted from the Langerhans islets of thepancreas and controls glucose metabolism.
o IDDM is caused by the autoimmune destruction of insulin-producing -cells of the pancreas, resulting in the inability tocontrol the blood glucose concentration.
Glucose-responsive hydrogels:
attractive candidates as an artificial pancreas that can release insulin inresponse to the blood glucose concentration.
Most strategies:
utilize the changes in physicochemical properties of hydrogel network
induced by glucose recognition.
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Glucose oxidase-immobilized DEAHPMA copolymer
the copolymer of diethylaminoethyl methacrylate (DEA) and 2-
hydroxypropyl methacrylamide (HPMA) as a pH-responsive polymer
1) When glucose diffused into the DEAHPMA copolymer membrane, it wasconverted to the gluconic acid by the catalytic reaction of glucose oxidase.
2) The produced gluconic acid decreased the microenvironmental pH within the DEAHPMA copolymer membrane and it swelled due to ionization of the tertiary amino
groups of DEA.
3) Thus, insulin permeation through the DEAHPMA copolymer membrane strongly
depended on the glucose concentration.
pH-responsive networks + glucose oxidase
Shinohara, I. Polym. J. 1984, 16, 625631
Many other glucose-responsive hydrogel
Literature Review/Design Presentation
On next Tue, Mar 25th
By Ishita Jain and Emily Sutton
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From Charge to Enzyme
Hydrogels Using Enzymatically
Derived/Eliminated Charged Groups
Diffuse Dense cytoskeleton
Apoptosis Proliferation
Stiffness
Size
FundamentalQuestions
to
Answer:
Howcellsbehaveinmechanically dynamicenvironment?
Cell Mechanobiology, Mechanotransduction,Cytoskeletaldynamics
Cell culture materials Petri dish Natural ECM Artificial ECM
2D semi-3D 3D (3D+ time) 4D?
Static Dynamic
Chris Chan et al, Nature 2011
Anseth et al, Science, 2009
React to cellular mechanical and chemical signals Spatio-temporally tunable
strain
Gel: homogeneous@nanocellular response to gel structure
& mechanics:
heterogeneous@micro
Mechanics spatio-temporally
Assaying Stem Cell Mechanobiology on Microfabricated
Elastomeric Substrates with Geometrically Modulated Rigidity
4-D Cell Culturing
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Enzyme-responsive hydrogels: swell
selective enzyme-triggered charge-induced swelling of the enzyme-
responsive hydrogels with thezwitterionic peptide linkers that arehydrolyzed by a specific enzyme
PEG-based hydrogels withenzymatic cleavable peptide (Fmoc-
Asp-Ala-Ala-Arg) which is hydrolyzed
by thermolysin.
Swelled specifically in response tothermolysin because doubly
charged peptide fragmentswereproduced by the enzymatic reaction
The dextran and avidin physically entrapped within hydrogel werereleased during hydrolysis of peptide chain by thermolysin
Enzyme-responsive hydrogels: shrink
Enzyme-responsive hydrogels that shrink in the presence of atarget enzyme were also prepared using charged peptide chainsthat were enzymatically decomposed.
The hydrogels shrank in the presence of a target enzyme becausepositively charged moieties of peptide chains were eliminatedfrom the hydrogel networks by enzymatic hydrolysis.
Applications of enzyme-responsive hydrogels that swell or
shrink in response to a target enzyme: Selective therapeutic release of drugs at specific sites
Such as a cancer site in which cancer-specific enzyme is
secreted
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Hydrogels with Enzymatic Cleavage of Networks
ECM-mimicking hydrogels composed of PEG-based hydrogelcrosslinked by the oligopeptides which are cleavable by thematrix metalloproteinases (MMPs).
Critical Properties:
Response speed
Response degree/Swelling ratio
Mechanical properties: hardness,elasticity, toughness, ductility
Hydrogel: Properties
Fast
Significant
Robust
Determinative Factors:
Type of stimuli: mechanism
Chemical composition
Crosslinking type and density
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Hydrogel: Characteristics
a b c
d e f
g h i
All scale bars = 5 mm
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Crosslinking type: chemical, small molecule or polymer/nanoparticles (nanogels)
responsiveness,
mechanical strength
Crosslinking density
Pore size
Mechanical strength
Chemical composition
Type of stimulus
Mechanical strength
Hydrogel:More varieties
New materials: molecular level
Polymer matrix
Different responsive moieties
Bio-functional groups
Composites: inter-molecular level
Carbon nanotubes
Colloids
Proteins, cells, drugs
Hybrids: micro/nano level
Structuring
Patterning
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The double-network gel V. S. Interpenetrating Polymer Network (IPN)
(with covalent bond) (without covalent bond)
Composite: Highly stretchable and tough hydrogels
covalent
crosslinks
Ionic
crosslinks
Z. Suo, et al. Science 2012
covalent
crosslinks
alginate gel polyacrylamide gel
Questions?
Hybrid: Micromirrors for Smart Windows
micromirror
array
thermo-responsive
hydrogel
muscle
transmittanceincreases with
cooling
macroscopic change in light
transmittance and reflectivity as
a function of temperature
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Gum bear?
self-heal in aqueous environment, bind in seconds
and form a bond st rong enough to withstand repeated
stretching molecular level velcro for drug delivery
(stomach)
Mimic the adaptiveness
Disruptive coloration -- Adaptive character create materials thatchange colors, or its invisible and visible again.
Our Mimicry system: HAIRS hybrid actuatable integrated responsive surfaces
Aizenberg et al. Soft Matter (2010)
Complex, spiral actuation of the
posts in the microflorets patterninduced by a chiral defect.
* chirality:to describe an object that isnot superposable on its mirror image
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Echinoderm
on YouTube
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How to realize adaptiveness?
- using responsive hydrogels as artificial muscle
P. Kim, L. Zarzar, X. He, et al. Current Opinion in Solid State & Materials Science (2011)31
Creating Adaptively Reconfigurable Systemshigh-aspect ratio (HAR) structured, passive skeletal materials
+hydrogel muscle
= Reversibly reconfigure and bend the embedded nano/microstructures, Providing a means to switch surface properties in response toenvironmental cues.
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How to graft gel to high-aspect-ratio posts?
Covalent bond
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(glycerol methacrylate)
How to make the adaptive disruptive coloration?
Note a clear color change during the
actuation.
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Dry state Dry to wet
WetWet to dry
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Decoding and Beating Heart
Aizenberg et al.Angew. Chem. (2011)35
How to encode?
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A laser (an acronym forLight
Amplification by Stimulated
Emission of Radiation) is a device
that emits light (electromagnetic
radiation) through a process of
optical amplification based on the
stimulated emission of photons.
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Integration of Hybrid Surfaces with Fluidic Systems
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Combinatorial Approaches
Structural and Chemical Manipulation of Actuation Dynamics Directionality Pattern
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Control of Directionality
Aizenberg et al. Soft Matter(2012)39
Warm-blooded Plastics
- Synthetic Homeostatic Materials
Motivation:
Homeostasis: ability to self-regulate local state --
Feedback-regulated chemo-mechano-chemical processes
Challenge:Only CM or MC, no CMC
Integration within hierarchical regimes by nano/microstructures
Compartmentalization and partition by hybrid design Dynamically coupling fast mechanical action and chemical inputs and
outputs by adaptively responsive soft materials
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Body temperature
Blood pressureControl center
Effecter
(actuate)
(Sense)
Receptor
Musclecontractionmyosinmotor
ATP synthase
GasLightHeat
Chemo Mechano
Fratzl, P. Nature (2009)
Stuart, M. A. C. et al. Nature Materials (2010)
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Creating Homeostasis via C-M-C feedback loop
Catalytic exthothermic reaction+
Temperature -responsive gel
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ONOFF
M
C2
C1
reagentscatalyst
aqueous solutionhydrogel
epoxy
X. He, A. Balazs, J . Aizenberg, et al. Nature (2012)
Movie
YouTube Movie
Effects of Key Parameters on Homeostasis
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12 m 15 m:
Tips remain in top layer for shorter time low
Thomeo smallerT smallerZ
Higher Zinterface lower Thomeo, higher Zave aroundZinterface
18 m 14.5 m:
Lower aspect ratio low actuation speed largerT smallerZ
Relatively higher Zinterface lower Thomeo,
Zhomeo still around Zinterface
liquid interface height microstructure height
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Effects of heating rate on homeostasis
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1-hexene:Triethylsilaneby H2PtCl6)(neat)
(i) (iii) (iv)
CumenehydroperoxideDecomp.by Ph3CPF6
Click reactionOctyl azide +Phenylacetyleneby Cu(PPh3)2NO3
higher heating rate higher ; larger T; larger Z
1-hexene:triethylsilane(80% in tol.)
(i)-dil. (i) (ii)
1-hexene:triethylsilane(neat)
1-hexene:diphenylsilane(neat) (all by H2PtCl6)
lower heating rate lower ; smaller T; smaller Z
heating rate other exothermic reactions
SMARTS - self-regulated mecho-chemical adaptively reconfigurable tunable surface
A large diversity of homeostatic systems can be designed with various regulatory
functions(temperature, pH, light, glucose, etc.) for advanced energy-efficient,
"smart" materials and devices
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Functions:
Switch/controller
Converting
Mimicking
Sorting
Functions:
Switch/controller
Converting
Mimicking
Sorting
Features:
Self-powering
Self-oscillating
Self-regulating
Features:
Self-powering
Self-oscillating
Self-regulating
C M
actuating
sensing
Demonstrated:
Physical effect
Biochem reaction
Inorganic chem reaction
Organic chem reaction
Demonstrated:
Physical effect
Biochem reaction
Inorganic chem reaction
Organic chem reaction
bioluminescence gasfluorescence self-oscillation
Conclusions
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Summary of Lecture 3
1. Bioinspiration:Adaptive, Reconfigurable, Dynamic
2. Bioinspired Materials: Stimuli-Responsive Hydrogels
Type 1: Charged groups in hydrogel network:
by changes in osmotic pressure
a change in pH induces dissociation of electrolyte groups,followed by charge-induced swelling of hydrogels
Humidity-, pH-, and temperature- responsive hydrogels
Type 2: Enzymatic production of charged groups:
also applicable to the designs of biologically stimuli-responsive
hydrogels that swell or shrink in the presence of a target enzyme Glucose- and enzyme-responsive hydrogels
3. Areas of Applications
Reading Resources
Reference Book 3: Intelligent Stimuli-Responsive Materials
Aizenberg Lab:
http://aizenberglab.seas.harvard.edu/ Research overview Topic:Adaptivehybrid architectures
Wyss Institute for Biologically-Inspired Engineeringhttp://wyss.harvard.edu/
YouTube: Username SMARTSmaterial
Amazing Bioluminescent/Glowing Deep Sea Creatures
Comb Jellyfish
What are the Cilia ?
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MSE 598/494 Bio-inspired Materials and BiomaterialsMSE 598/494 Bio-inspired Materials and Biomaterials
Instructor: Ximin He
TA: Xiying Chen Email: [email protected]
2014-04-20
Lecture 4. Smart Stimuli-Responsive Materials I
Biomimetic Self-oscillating Polymer gels
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Antimicrobial materials for Anti-biofilm/fouling
for marine and biomedical application
Credit: Centers for Disease Control and Prevention
Marine Fouling Bacterial Fouling
WikipediaAlex Epstein, et al. PNAS (2010) and (2012)
Current methods:
Copper
Pulsed laser irradiation
High energy acoustic pulses
New trend- new funct. mater.
by mimicking marine
animals
Challenges:
Passive repellenceActive
Non-toxic mechanic strategy
Environment-friendly
Effective
Energy-efficient
Long-term anti-biofouling
stabilities
Motivation:
Natures strategy:Active Repellenceusing periodic motion of microstructure
/frog embryoBeating cilia on echinoderms
Direction 2
Respiratory tractand intestine
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Bio-inspired Autonomous Mass-transport and Microbial Repellenceusing periodic motion of microstructure
Novel
approach:
environment
friendly
Smart
Active
Antibiofilm
preventsettlement
and
activelyremovebybiomimeticautonomousmotion,withmolecularcontrol.
Duofunction:Antifouling+Dragreduction
i) vibrationdrivenbyaselfoscillatinglayer(tandemdesign)
ii) byselfoscillatinggelorcilia(hybriddesign)/gelontheotherside
ToRepel:
Bacteria:
Pseudomonasaeruginosa (Sepsis) themostfrequentcolonizerofmedicaldevices Staphylococcusaureus (Pneumonia,Sepsis) Escherichiacoli(FoodPoisoning)Marinebiofouling organism:
Barnacles/Ulva
Approaches
1. Nanoparticle-capturing actuator
2. Mechanical wave: P. aeruginosa biofilm, 24 hrs
Static : Dynamic:
X. He, et al.Adv. Func. Mater . 2006, Chem. Mater. 2013
3. Chemo-mechanical wave:
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Autonomous Motion with Self-oscillating Materials
Self-oscillating Chemical Reaction: Belousov-Zhabotinsky B-Z reaction
Chemo Mechano
(Youtube)
Homework:
Mechanisms of
i) B-Z reaction and ii) Self-oscillating gels
B-Z reaction based Self-oscillating Gel
Yoshida, et al.Adv. Funct. Mater. 2010
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Self-walking Robot
Youtube
Versatile Self-oscillating Polymer Gels
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Intestine-like autonomous mechanical pumping system
Schematic illustration of autonomous mass
transport by peristaltic pumping of a tubular self-
oscillating gel.
The behavior of the autonomous transport of a
CO2 bubble in the gel tube by peristaltic pumping.
Mass transport
by
peristaltic pumping
Sol-Gel transition by Autonomous viscosity oscillation
By reversible complex formation of terpyridine-terminated tetra PEG
(Poly(ethylene glycol)) in the BZ reaction.
BZ reaction induces the periodical binding/dissociaion of the Ru-terpyridine
complex and causes periodic molecular weight changes and results in
viscosity changes.
terpyridine-terminated tetra PEG
terpyridine-terminated PEG
Oscillating profiles of viscosity of the aqueous solution
containing Ru(terpy)2-tetra PEG, HNO3, NaBrO3, andMA at 25 oC.
Sol-Gel transition
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Toward Applications
Limitation? Operating conditions for the self-oscillation are limited to
conditions under which the BZ reaction occurs
For potential applications as functional bio- or biomimetic
materials?
Design a self-oscillating polymer which acts under biologicalenvironments.
Solutions?
1. Operate in Physiological Media
Solutions:
To built BZ substrates other than organic ones, such as malonicacid and citric acid into the polymer system itself.
Examples :
synthesized a quaternary copolymer which includes both pH-control and oxidant-supplying sites in the poly(NIPAAm-co-Ru(bpy)3) chain at the same time. By using this polymer, self-
oscillation by adding only the organic acid (malonic acid) wasactually observed.
Yoshida, R. Self-oscillating polymer fueled by organic acid. J. Phys. Chem. B 2008, 112, 84278429.
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2. Operate at Body Temperature
Challenge:the volume phase transition temperature of the poly(NIPAAm-co-
Ru(bpy)3) gel is around 25C, and above that temperature the gelshrinks for both the reduced and oxidized states
Solution 1:
To utilize a non-thermosensitive polymer without an LCST?
Problem:
The difference in swelling ratios between the reduced and oxidizedstates rely only on a change in hydrophilicity due to the chargenumber of the redox site without the help of an attractiveintermolecular force by phase transition.
Yoshida, R. Self-oscillating polymer fueled by organic acid. J. Phys. Chem. B 2008, 112, 84278429.
2. Operate at Body Temperature
Solution 2:
by using a thermosensitive polymer with a
higher LCST
to maintain a large difference between thereduced and oxidized states by utilizing thephase transition at higher temperatures:poly(EMAAm-co-Ru(bpy)3) gel
Successfully induce self-oscillation while
maintaining a larger amplitude at highertemperatures and around body temperature
Yoshida, R. Self-oscillating polymer fueled by organic acid. J. Phys. Chem. B 2008, 112, 84278429.
* N,N-ethylmethylacrylamide (EMAAm)* N,N-dimethylacrylamide (DMAAm)
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Homework of Lecture 3-4 on 03/20/2004
1. Please name some pH-responsive hydrogels and temperature-responsive hydrogels, and explain the mechanism of theirresponsiveness.
2. Please state the mechanisms of i) a B-Z reaction and ii) theself-oscillating gels in general.
Due by 04/01/2014
Hand in hard copy of homework at the TA, Xiying Chen, at thebeginning of the class on 04/01/2014
Please contact [email protected] for questions.