7 Smart Polymers - Kinam Park

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

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


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


Polymer Volume Fraction0 1

Temp

1 Phase

UCST

LCST

2 Phases

Soluble

Insoluble

Soluble

(Hydrophobic Interaction)

Soluble Insoluble Soluble


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


Effect of L:G Ratio


Effect of PEG Molecular Weight


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.


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


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

7 Smart Polymers - Kinam Park

Documents

Transcript of 7 Smart Polymers - Kinam Park