Lect 3-4-140320 Hydrogels_print

8/11/2019 Lect 3-4-140320 Hydrogels_print

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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

2


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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

5

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

7

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:

11

Preparation

Synthesis:

Solution-based polymerization

Cast into any shape

cross-linkermonomer

initiator

or

12

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:


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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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

25

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?

36

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

41

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

42

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.


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


* 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.

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Lect 3-4-140320 Hydrogels_print