7 smart polymers - kinam park
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Smart Polymers & Hydrogels
Ordinary Polymers & Hydrogels Smart Polymers & Hydrogels(Environment-sensitive, Stimulus-responsive)
Swelling-Shrinking
Sol-gel phase transition
Degradation
Shape transformation
PolymersPrecipitation DissolutionContraction Expansion
Shrinking Swelling
Hydrogels
Respond to minute changes in environmental conditions by large and sharp changes in physicochemical properties
Environmental StimuliPhysical
Chemical
Biological
Stimuli
Smart Polymers & Hydrogel Prof. You Han Bae, University of Utah
Soluble
Collapsed Gel
Insoluble
Swollen Gel
Solution Physical Gel
SIGNAL
(pH,T,I,
Biomol)\][kjhl;
BasicResearch
Solution Injection
Embolic Material
Applied Research
Soft Actuator
Pulsatile Drug Release
Immunoassay
Membrane SeparationProtein Drug Loading
and Release
Bioreactor
E E
Hydrophobic Chromatography
Tumor Targeting
Sensor, Biosensor
Drug Delivery Bioseparation
Biosensor Tissue Engineering
.
Cell culture & Harvest
..
Enzyme activity
Intelligent Gels
Intelligent Gels
Bionic Pancreas
The Next Best Thing to a Cure for DiabetesAlexandra SifferlinTIME Jan. 29, 2015
Wound Care
Everyday Plastics
Polymer Microrockets
Changes in Solubility
Temperature Sensitive Systems
Temperature-Sensitive Polymers & Hydrogels
Positive Thermosensitivity
as T ↑ Solubility/Swelling ↑
Negative Thermosensitivity
as T ↑ Solubility/Swelling ↓
Competition between the two forces(H-bonding & Hydrophobic interaction)
Temperature dependent interactions
Covalent bond: ~ 5 eV (≈ 0.8 x 10-18 J)
Secondary interaction forces: ~ 0.1 eV
Thermal fluctuation energy: ~ 0.03 eV (≈ 1 kT)
as T ↑ Hydrogen-bonding ↓
as T ↑ Hydrophobic interaction ↑
Hydrophobic interactions
A droplet of water forms a spherical shape to minimize contact with the hydrophobic leaf.http://en.wikipedia.org/wiki/Hydrophobic_effect
http://academic.brooklyn.cuny.edu/biology/bio4fv/page/hydropho.htm
Hydrocarbons.Lipophilic hydrocarbon-like groups in solutes.
Poly(N-isopropyl acrylamide) (PNIPAAm)
The first smart polymers.Temperature-dependent polymers.
Lower critical solution temperature: lowest temperature at which all components of the system are soluble
Solution: Soluble InsolubleHydrogel: Swollen CollapsedSurface: Hydrophilic Hydrophobic
Adjusting the LCST of PNIPAAm
Am: acrylamide
N-tBAAm: n-tertbutylacrylamide
Temperature-Sensitive Polymers & Hydrogels
C C
H
H
H
C O
NR 1 R 2
HN
HN CH
CH 2
CH 2
HN CH
CH 2
CH 2
HN C
CH 2
CH 2
CH 2
CH 2
CH 2
CH 2
CH 2
HN CH
CH 3
CH 3
NH
CHC 2 H 5
C 2 H 5
NC 2 H 5
CH 3
NCH
CH 3
n
CH 3
C lo u d T e m p . (o C )
(4 5 .5 )
HN CH 2 CH 2 CH 3 N
CH 3
CH 2 CH 2 CH 3
C 2 H 5
(7 2 .0 )
(5 .5 )(5 6 .0 )
(3 0 .9 ) (3 2 .0 )
(5 6 .0 ) (2 2 .3 )
(2 1 .5 ) (1 9 .8 )
a d o p te d f ro m S . Ito , K o b u n sh i R o n b u n sh u , 4 6 (1 9 8 9 ) 4 3 7
H 3 C
C C
H
H
R 1
C O
NH R 2
CH 2 O CH 2 O CH 3
CH 2 O CH 3
CH 2 O C 2 H 5
CHCH 3
CH 2 O CH 3
CH 2 O C 2 H 5
CH 2O
CH
n
C 2 H 5
CH 2
C lo u d T e m p . (o C )
R 2
O
R 1 = C H 3
CH 3
R 1 = H
CH 2
3
O
3
CH
3
2
CH 3
CH 3
3
3
8 4 .0
6 3 .5
4 5 .5
4 2 .6
3 8 .5
3 3 .0
1 4 .0
1 3 .0
7 9 .0
4 4 .5
3 5 .0
3 3 .5
2 4 .3
2 7 .7
1 1 .0
8 .7
a d o p te d f ro m S . Ito , K o b u n sh i R o n b u n s h u , 4 7 (1 9 9 0 ) 4 6 7
Temperature-Sensitive Polymers & Hydrogels
Polymer Volume Fraction0 1
Temp
1 Phase
UCST
LCST
2 Phases
Soluble
Insoluble
Soluble
(Hydrophobic Interaction)
Soluble Insoluble Soluble
Temperature-Sensitive Polymers & Hydrogels
Case study:
A veterinary company asks you to design a drug delivery platform for reptiles and another one for rodents. You decide to make it using NIPAAm, how would you have to modify the system to work for your needs?
Applications as a Bio-Conjugate
E E
EE
Recovery of Product
T>LCST
T<LCST
T>LCST, Centrifuge
T<LCST
Add Substrate
+Product
Suspension of conjugate and productRe-dissolve
and Recycle
Ding, 1998 J Biomed Mater Res
Protein is conjugated to the polymer.
Bioactivity normally decreases.
Can add to a site specific location, but difficult to do.
Applications in Tissue Engineering
Teruo Okano (Professor, Tokyo Women's Medical University)
Applications in Drug Delivery…Limited!Polymers: Hydrophilic (Water-soluble)
Hydrophobic (Water-insoluble)Hydrogels: Network of hydrophilic polymersOrganogels: Network of hydrophobic polymers
Ordinary Polymers & Hydrogels
Shrunken state- Squeezing- Trapping
Swollen state- Opening- Absorbing
Crosslink
Drug
Precipitation Dilution
Thermo-sensitive Polymers
PEG-PLGA-PEG Triblock Copolymer
Thermogelling system capable that can be used for drug delivery
PLGA is a biocompatible hydrophobic polymer commonly used in controlled release devices
PLGA is biodegradable
PEG is a biocompatible hydrophilic polymer used for a number of applications
Macromolecules 1999, 32, 7064-7069
PEG-PLGA-PEG Triblock Copolymer: Predict the Response
Effect of PLGA Molecular Weight
PEG-PLGA-PEG Triblock Copolymer: Predict the Response
Effect of L:G Ratio
PEG-PLGA-PEG Triblock Copolymer: Predict the Response
Effect of PEG Molecular Weight
PEG-PLGA-PEG Triblock Copolymer: Predict the Response
Effect of the Solvent
PEG-PLGA-PEG Triblock Copolymer Overall Behavior
gel
sol30 oC
70 oC
10%Polymer conc. wt%
Temperature
PLGA PEG
Polymer conc. wt%
Temperature
The more hydrophobic the lower the Sol temperature.The more hydrophilic the more polymer that could be added to the solution.
Changes in Solubility
pH Based Systems
pH-Sensitive Systems
Low pH High pH
O O
NHM e 2
M e
O O
NM e 2
M e
CO 2 H CO 2
OH
H 3 O
OH
H 3 O
Water-insoluble,Collapsed
Water-soluble,Expanded
Water-insoluble,Collapsed
Water-soluble,Expanded
pH-Sensitive Polymers (Polyelectrolytes)R
elat
ive
Swel
ling
Rat
io
pH
1 2 3 4 5 6 7 8 90 .0
0 .2
0 .4
0 .6
0 .8
1 .0
CH 2 C CH 2C O mn
CH 3
O
CH 3
CH
C OOCH 2CH 2
NC 2 H 5C 2 H 5
CH 2 C CH 2C O mn
CH 3
O
CH 3
CH
C OOCH 2CH 2
NC 2 H 5C 2 H 5
H
+
Ionized
Neutral
pH-Sensitive Polymers (Polyelectrolytes)
Monomer pH-sensitive
group
Acidic (Meth)acrylic acid -COOH
(Anionic) Sodium styrene sulfonate -SO3- Na+
Sulfoxyethyl methacrylate -SO3H Aminoethyl (meth)acrylate -NH2 N,N-dimethylaminoethyl
(meth)acrylate -N(CH3) 2
Basic (Cationic)
N,N-diethylaminoethyl (meth)acrylate
-N(CH2CH3) 2
Vinylpyridine
Vinylbenzyl triethylammonium chloride
-N+(CH3)3Cl-
Brondsted and Kopecek, ACS Symp. Ser. 480, pp. 285-304 (1992)
N
pH-Sensitive Polymers
Bulk Solution
Polymer Matrix
Released insulin
Loaded insulin
Glucose
Glucoseoxidase
Gluconic acid
Collapsed polymer
Expanded polymer
Polymer-COO- Polymer-COOH
Glucose Sensitive Devices
pH 8
pH 4
I
I
I I I
III
I
I
II III II IIIII III II III II III II III
II III II III
pH Sensitive polymers blocking the diffusion of Insulin from a reservoir.
The polymer changes in response to the actions of GOD.
Chamber
Chamber IIDiaphragm
MovablePartition
Chamber III
Orificewithvalve
Housing(a) Glucose Sensitive
Swellable Hydorgel
Screen
One WayValve
InsulinFormulation
(b)
BloodGlucose
Up
BloodGlucoseDown
(c)
KineticsReproducibility
Glucose Sensitive Devices
Self-Regulated Systems
Changes in Environmental Factors
Sensor
Information Processor
Actuator
Glucose sensor
Insulin release
Feedback
Feedback: Stop insulin release
Glucose level changes in blood
Determine theamount of insulinto be released
Accurate timing
Specificity, sensitivitySpeed
Accurate dose
ReversibilityRepeatabilityMagnitude
SafetyBiodegradability
Self-Regulated Systems
Open-loop system Closed-loop system
Changes in Solubility
Light Responsive Systems
NN
h v
h v ' o r N
N
tra n s c is
a z o b e n z e n e
N
MeMe
MeO NO 2
h v
h v ' o r N
MeMe
MeO NO 2
c lo s e d r in g o p e n r in gs p iro p ira n
COH
N NCH 3
CH 3
H 3 CH 3 C
h v
CN N
CH 3
CH 3
H 3 C
H 3 C
OH
tr ip h e n y lm e th a n e (m a la c h ite g re e n le u c o h yd ro x id e )
n o n io n ic io n ic
P h o to - in d u c e d s tru c tu ra l c h a n g e s o f p h o to c h ro m ic c o m p o u n d s
Light
gel
Light
Photochemistry and Photobiology, 2009, 85: 848–860
Light-sensitive Polymer and Hydrogels
Which form will result in precipitation of the polymer?
Light-sensitive Polymer and Hydrogels
Acetylated Dextran is not soluble, the acetylation is sensitive to acidic conditions
Light induces a change in pH solubalizing the dextran
Small 2013, 9, No. 18, 3051–3057
Irreversible Light-sensitive systems
Stimulus Response to Electric and Magnetic Fields
Stress-Sensitive Polymers
Electrifying Plastics
Tris(8-hydroxyquinolinato) aluminium
Poly(p-phenylene vinylene)
Organic Light-Emitting Diode Graphene
http://www.rsc.org/images/RSCelectro_tcm18-159224.pdf
http://phys.org/news/2015-09-chameleon-inspired-stretchable-e-skin.html
The researchers developed a thin, clear nanocellulose paper made out of wood flour and infusaed it with biocompatible quantum dots—tiny, semiconducting crystals—made out of zinc and selenaium. The paper glowed at room temperature and could be rolled and unrolled without cracking.
http://www.rdmag.com/news/2015/05/toward-green-paper-thin-flexible-electronics?et_cid=4581167&et_rid=54728378&location=top
Conventional electroluminescent (EL) foils can be bent up to a certain degree only and can be applied easily onto flat surfaces. The new process developed by Karlsruhe Institute of Technology (KIT) in cooperation with the company of Franz Binder GmbH & Co. now allows for the direct printing of electroluminescent layers onto three-dimensional components. Such EL components might be used to enhance safety in buildings in case of power failures. Other potential applications are displays and watches or the creative design of rooms. The development project was funded with EUR 125,000 by the Deutsche Bundesstiftung Umwelt (German Foundation for the Environment).
http://www.rdmag.com/news/2015/05/new-printing-process-makes-three-dimensional-objects-glow?et_cid=4581167&et_rid=54728378&type=cta
‘Green' Paper-Thin, Flexible Electronics
New printing process makes three-dimensional objects glow
Electrochromic Polymers
http
The
Wearable Electronics
NanoSonic’s Metal Rubber™ is a highly electrically conductive and highly flexible elastomer. It can be mechanically strained to greater than 1000 percent of its original dimensions while remaining electrically conductive. As Metal Rubber can carry data and electrical power and is environmentally rugged, it opens up a new world of applications requiring robust, flexible and stretchable electrical conductors in the aerospace/defense, electronics and bioengineering markets.
http://www.nanosonic.com/80/4/metalrubber.html http://videos.howstuffworks.com/sciencentral/2938-metal-rubber-video.htm Popular Science. August 2004. p. 36.
Metal Rubber
A change in shape or volume occur in response to an applied voltage
Dielectric elastomer actuators (silicone), ferroelectric polymers (poly(vinylidene fluoride)) , electrostrictive graft elastomers (P(VDF-TrFE) polar side chains), conducting polymers, ionic polymer metal composites (perfluorinated alkenes)
Materials Today 10(4) 2007, 30-38
Electro-responsive Polymers and Hydrogels
Electro-responsive Polymers and Hydrogels
https://youtu.be/ScoQf_dNyls
Magnetic Hydrogel for Controlled Release
www.pnas.org/cgi/doi/10.1073/pnas.1007862108
Magnetic Hydrogel for Controlled Release
Satarkar NS and Hilt JZ J Control Release 130: 246, 2008
Shape Memory Polymers
Shape memory polymers have 2 key identifying features
Shape fixity Shape recovery
Shape fixity allows the material to maintain a temporary shape after molding
Shape recovery allows the material to return to the original shape of the material
Important Aspects of Shape Memory Polymer Systems
Is It A Shape Memory Polymer?
Poly(glycerol-dodecanoate)-Related to poly (glycerol sebacate)-Elastomer-Hydrolytically cleavable-Tg~32°C
J. Biomed. Mater. Res.. Accepted Author Manuscript. doi:10.1002/jbm.a.35973
Shape Memory Polymers for Heart Repair
Angew. Chem. Int. Ed. 2012, 51, 660 –665
Stimulus allows for folding of a polymer into predefined shape in response to an external stimulus
Polymer Origami
Science Advances 08 Jan 2016: Vol. 2, no. 1, e1501297 DOI: 10.1126/sciadv.1501297
Polymer Origami
Adv. Mater. 2015, 27, 79–85
Polymer Origami
• Smarter materials: • proteins, peptides, DNAs, hybrid materials
• Smarter response: • multiple stimuli-sensitivity, new stimuli
• Smarter function: • cell-free enzyme synthesis, microfabrication, extracellular
matrix, bioseparation, actucation, sensor
Getting Smarter
Kopeček J Biomaterials 2007Wang et. Al. Nature 1999
Polymer-peptide Hybrid Hydrogels
Thornton. et al. Soft Matt 4: 821, 2008
Albumin release Albumin releaseAvidin releaseAvidin release
Enzyme-responsive Hydrogel Nanoparticles
Cohen Stuart, et al. Nat Mater 9: 101, 2010
Stimuli-responsive Nanoparticles for Drug Delivery
Cohen Stuart, et al. Nat Mater 9: 101, 2010
‘Galaxy’ of Stimuli-responsive Polymers
Faster
Getting Smaller
Natural Systems Synthetic Systems
Survival
Biological Need
Miniaturization
Clinical Efficacy
Efficacy,Simplicity(Bottom-up)
DiffusionSelectivity(Top-down)
Mimicking Biosystems
Material development: Smart hydrogels with high IQ
Find applications:
Mismatch between material properties and application
Target application: Understand physiological
requirements
Clinical success:
Faster translation to clinical formulations
Current Future
Menciassi 2018, Swell findings in hydrogels
Swell Findings in Hydrogels
Polymers in Technology
http://acadia.org/papers/2QPH7Y http://www.nature.com/articles/srep31110
Shape Memory Polymers in Aerospace Applications
Variable stiffness shape memory polymer triggered by both Joule heating and dielectric loss NASA's Langley Research Center has developed a novel shape memory polymer (SMP) made from composite materials for use in morphing structures. In response to an external stimulus such as a temperature change or an electric field, the thermosetting material changes shape, but then returns to its original form once conditions return to normal. Through a precise combination of monomers, conductive fillers, and elastic layers, the NASA polymer matrix can be triggered by two effects--Joule heating and dielectric loss--to increase the response. The new material remedies the limitations of other SMPs currently on the market--namely the slow stimulant response times, the strength inconsistencies, and the use of toxic epoxies that may complicate manufacturing. NASA has developed prototypes and now seeks a partner to license the technology for commercial applications.
https://technology.nasa.gov/patent/LAR-TOPS-39http://www.azom.com/article.aspx?ArticleID=13516
Electric field activated shape memory behavior of variable stiffness polymer composite (VSPc). (a) permanent shape, (b) programmed temporary shape, and (c) recovered permanent shape (inset: infrared images).
Electroactive polymers (EAPs) are a type of flexible, elastic polymer (elastomer) that change size or shape (i.e., bend, contract or expand) when stimulated by an electric field. EAPs are generally categorized by their mode of activation: electronic or ionic. Electronic EAPsinclude electrostrictive elastomers and dielectric electroactive polymers (DEAPs), while an example of an ionic EAP is the ionic polymer metal composite (IPMC). In electronic EAPs, the electric field applies coulomb attractive forces to the electrodes. This causes the change in size and shape due to compressive forces. With ionic EAPs, the mobility and diffusion of ions changes the shape.
Shape Adaptive Multilayered Polymer Composite
Harper Meng, Guoqiang Li. A review of stimuli-responsive shape memory polymer composites. Polymer 54: 2199-2221, 2013.
Fig. 1. Various molecular structures of SMPs. A stable network and a reversible switching transition are the prerequisites for the SMPs to show SME. The stable network can be molecule entanglement, chemical cross-linking, crystallization, and IPN; the reversible switching transition can be crystallizationemelting transition, vitrificationeglasstransition, anisotropiceisotropic transition, reversible chemical cross-linking, and associationedisassociation of supramolecular structures
The sequential recovery of the epoxy/polycaprolactone composite (A) from a temporary shape, (B) to temporary shape b, and (C) to permanent shape c.
Stimuli-responsive Shape Memory Polymer Composites
5.1. Stimuli-memory effect of SMPCs5.1.1. Temperature-memory effect of SMPCsTemperature-memory effect means the shape memory material can memorize the temperatures at which it is programmed [243]. Temperature-memory effect of SMAs has been widely studied. Miaudet et al. [290] first reported the temperature-memory effect of SMPs on shape memory polyvinyl alcohol composites with a broad glass transition. For SMPs with broad glass transition, the broad glass transition may be regarded as the consecutive distribution of a number of glass transitions [461]. According to the mechanism of SME, if the polymer is deformed at a temperature above the glass transition temperature and heated again to the temperature, the polymer recovers. The “remembered” temperature may not be the exact temperature that it is programmed; there may be some quantitative relationship. Xie et al. [518] also demonstrated the temperature-memory effect of Nafion with a broad glass transition temperature. Theoretically, the temperature memory effect can also be found in SMP with a melting transition temperature as the switching temperature as long as the melting transition is broad, which has been demonstrated by Kratz et al.[460].
Fig. 16. Chemical structure of “coil-like” polyarylamide block “coil-like” poly(ethylene oxide).
Stimuli-responsive Shape Memory Polymer Composites