Smart Polymers & Hydrogels. Purdue University Biomedical Engineering. Professors Kinam Park & Luis Solorio

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1 Smart Polymers & Hydrogels Purdue University Biomedical Engineering Professors Kinam Park & Luis Solorio

2 Smart Polymers Stimulus/responsive polymers 1. Property change is sharp 2. Property change is large 3. Stimulus required is small Reversible Precipitation + Stimulus Reversible Collapse + Stimulus - Stimulus - Stimulus Reversible Adsorption + Stimulus Reversible Gel Collapse + Stimulus - Stimulus - Stimulus Biomaterials Science: An ntroduction to Materials in Medicine 2 nd Addition

3 Environmental Stimuli Physical Stimuli Biological Chemical

4 Prof. You Han Bae University of Utah Drug delivery Protein Drug Loading and Release Tumor Targeting Solution njection Bioseparation Embolic Material Membrane Separation Pulsatile Drug Release Soluble SGNAL nsoluble Hydrophobic Chromatography Swollen Gel (ph, T,, Biomol) Collapsed Gel E E Soft Actuator Biosensor Sensor, Biosensor Enzyme activity mmunoassay Solution Basic Research Applied Research Physical Gel.. Cell culture & Harvest Bioreactor Tissue.. Engineering ECM for 3-D Cell Culture

5 ntelligent Gels

6 ntelligent Gels

7 Bionic Pancreas The Next Best Thing to a Cure for Diabetes Alexandra Sifferlin TME Jan. 29, 2015

8 Wound Care

9 Everyday Plastics

10 Polymer Microrockets

11 Smart Polymer Publications Based On Keyword Search (Google Scholar) Cummulative Number of References Key word: Smart Polymer Cummulative Number of References Key word: Shape Memory Polymer Cummulative Number of References Year Key word: Polymer Origami Year Cummulative Number of References Year 8000 Key word: Polymer Origami Year

12 Changes in Solubility Temperature Sensitive Systems

13 Temperature-Sensitive Polymers & Hydrogels Positive Thermosensitivity as T Solubility/Swelling Negative Thermosensitivity as T Solubility/Swelling Covalent bond: ~ 5 ev ( 0.8 x J) Secondary interaction forces: ~ 0.1 ev Thermal fluctuation energy: ~ 0.03 ev ( 1 kt) Competition between the two forces (H-bonding & Hydrophobic interaction) Temperature dependent interactions as T Hydrogen-bonding as T Hydrophobic interaction

14 Hydrophobic interactions Hydrocarbons. Lipophilic hydrocarbon-like groups in solutes A droplet of water forms a spherical shape to minimize contact with the hydrophobic leaf.

15 Poly(N-isopropyl acrylamide) (PNPAAm) Changes state in response to temperature Was among the first smart polymers Lower critical solution temperature: lowest temperature at which all components of the system are soluble Solution: Soluble nsoluble Hydrogel: Swolen Collapsed Surface: Hydrophylic Hydrophobic

16 Adjusting the LCST of PNPAAm Am: acrylamide N-tBAAm: n-tertbutylacrylamide

17 Temperature-Sensitive Polymers & Hydrogels H H H R 1 C H C C O n C H C C n O H N C 2 H 5 N R 1 R 2 Cloud Temp. ( o C) N H R 2 Cloud Temp. ( o C) (72.0) R 2 R 1 = CH 3 R 1 = H H N H N CH (45.5) CH CH 2 CH 2 CH 3 H NCH CH 3 N H CH CH 2 CH 2 (56.0) C 2 H 5 C 2 H 5 CH 2 CH 2 H N C CH 2 CH 2 (5.5) CH 2 CH 2 CH 2 CH 2 O CH 2 O 3 3 CH 3 CH 2 3 O CH 3 CH 2 2 O C 2 H 5 CH 3 CH (30.9) (32.0) CH 2 O CH 3 N C 2 H 5 CH 3 H 3 C CH N CH 3 CH 3 (56.0) (22.3) CH 2 3 O C 2 H 5 CH 2 O H N CH 2 CH 2 CH 3 N CH 3 CH 2 CH 2 CH 3 CH C 2 H 5 CH 2 O CH (21.5) (19.8) CH 2 3 O CH CH 3 CH adopted from S. to, Kobunshi Ronbunshu, 46 (1989) 437 adopted from S. to, Kobunshi Ronbunshu, 47 (1990) 467

18 Temperature-Sensitive Polymers & Hydrogels UCST Soluble Temp LCST 2 Phases (Hydrophobic nteraction) Soluble nsoluble nsoluble Soluble Soluble 1 Phase 0 1 Polymer Volume Fraction

19 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 NPAAm, how would you have to modify the system to work for your needs?

20 Applications as a Bio-Conjugate E T<LCST Add Substrate E +Product Re-dissolve and Recycle T<LCST Suspension of conjugate and product T>LCST Protein is conjugated to the polymer Bioactivity normally decreases E Recovery of Product T>LCST, Centrifuge E Can add to a site specific location, but difficult to do Ding, 1998 J Biomed Mater Res

21 Applications in Tissue Engineering Teruo Okano (Professor, Tokyo Women's Medical University)

22 Applications in Drug Delivery Limited! Polymers: Hydrophilic (Water-soluble) Hydrophobic (Water-insoluble) Hydrogels: Network of hydrophilic polymers Organogels: Network of hydrophobic polymers Ordinary Polymers & Hydrogels Drug Precipitation Shrunken state - Squeezing - Trapping Crosslink Dilution Swollen state - Opening - Absorbing

23 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,

24 PEG-PLGA-PEG Triblock Copolymer: Predict the Response Effect of PLGA Molecular Weight

25 PEG-PLGA-PEG Triblock Copolymer: Predict the Response Effect of GA:LA Ratio

26 PEG-PLGA-PEG Triblock Copolymer: Predict the Response Effect of PEG Molecular Weight

27 PEG-PLGA-PEG Triblock Copolymer: Predict the Response Effect of the Solvent

28 PEG-PLGA-PEG Triblock Copolymer Overall Behavior Temperature 70 o C 30 o C gel sol 10% Polymer conc. wt% The more hydrophobic the lower the /Sol temperature The more hydrophilic the more polymer that could be added to the solution Temperature PLGA PEG Polymer conc. wt%

29 Changes in Solubility ph Based Systems

30 ph-sensitive Systems Low ph OH High ph CO 2 H H 3 O CO 2 Water-insoluble, Water-soluble, Collapsed Expanded Me OH Me O O H 3 O O O Water-soluble, Expanded NHM e 2 Water-insoluble, Collapsed NM e 2

31 Crosslinked poly(mma-co-deaeam) (70/30 molar ratio) 1.0 onized CH 3 CH 2 C CH 2 CH C O n C O m O O CH 3 CH 2 Relative Swelling Ratio Neutral CH 2 N C 2 H 5 H C 2 H 5 CH 3 CH 2 C CH 2 CH C O n C O m O O CH 3 CH 2 CH 2 C 2 H 5 N C 2 H 5 + ph

32 ph-sensitive Polymers (Polyelectrolytes) Monomer ph-sensitive group Acidic (Meth)acrylic acid -COOH (Anionic) Sodium styrene sulfonate - -SO 3 Na + Sulfoxyethyl methacrylate -SO 3 H Aminoethyl (meth)acrylate -NH 2 N,N-dimethylaminoethyl -N(CH 3 ) 2 (meth)acrylate N,N-diethylaminoethyl -N(CH 2 CH 3 ) 2 Basic (meth)acrylate (Cationic) Vinylpyridine N Vinylbenzyl triethylammonium chloride -N + (CH 3 ) 3 Cl - Brondsted and Kopecek, ACS Symp. Ser. 480, pp (1992)

33 ph-sensitive Polymers Bulk Solution glucose released insulin glucose oxidase gluconic acid collapsed polymer loaded insulin poly mer CO 2 poly mer CO 2 H Polymer Matrix expanded polymer

34 Glucose Sensitive Devices ph 8 ph 4 ph Sensitive polymers blocking the diffusion of nsulin from a reservoir The polymer changes in response to the actions of GOD

35 Glucose Sensitive Devices (a) Glucose Sensitive Swellable Hydorgel One Way Valve nsulin Formulation Housing Screen Diaphragm Chamber Movable Partition Chamber Orifice with valve Chamber (b) Blood Glucose Up (c) Blood Glucose Down Kinetics Reproducibility

36 Self-Regulated Systems Changes in Environmental Factors Glucose level changes in blood Specificity, sensitivity Speed Sensor Glucose sensor Accurate dose nformation Processor Feedback Determine the amount of insulin to be released Accurate timing Reversibility Actuator nsulin release Repeatability Magnitude Feedback: Stop insulin release Safety Biodegradability

37 Self-Regulated Systems Open-loop system Closed-loop system

38 Changes in Solubility Light Responsive Systems

39 Light-sensitive Polymer and Hydrogels N N hv' or hv N N gel Light Light trans azobenzene cis Me Me hv Me Me N Me O NO 2 hv' or N Me O NO 2 closed ring spiropiran open ring H 3 C N C N CH 3 H 3 C OH CH 3 nonionic hv H 3 C N C N CH 3 H 3 C CH 3 OH ionic triphenylmethane (malachite green leucohydroxide) Photo-induced structural changes of photochromic compounds Photochemistry and Photobiology, 2009, 85:

40 Light-sensitive Polymer and Hydrogels Which form will result in precipitation of the polymer?

41 Light-sensitive Polymer and Hydrogels Which form will result in precipitation of the polymer?

42 Light-sensitive Polymer and Hydrogels Which form will result in precipitation of the polymer?

43 rreversible Light-sensitive systems 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,

44 Design Your Own Break into 2 teams Design a smart system Describe the system and the application

45 Stimulus Response to Electric and Magnetic Fields

46 Electro-responsive Polymers and Hydrogels A change in shape or volume occur in response to an applied voltage Materials Today 10(4) 2007, 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)

47 Electro-responsive Polymers and Hydrogels

48 Magnetic Hydrogel for Controlled Release

49 Magnetic Hydrogel for Cell Culture

50 Magnetic Hydrogel for Controlled Release Satarkar NS and Hilt JZ J Control Release 130: 246, 2008

51 Shape Memory Polymers

52 mportant Aspects of Shape Memory Polymer Systems 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

53 s t A Shape Memory Polymer?

54 Shape Memory Polymers for Heart Repair Poly(glycerol-dodecanoate) -Related to poly (glycerol sebacate) -Elastomer -Hydrolytically cleavable -Tg~32 C J. Biomed. Mater. Res.. Accepted Author Manuscript. doi: /jbm.a.35973

55 Polymer Origami Stimulus allows for folding of a polymer into predefined shape in response to an external stimulus Angew. Chem. nt. Ed. 2012, 51,

56 Polymer Origami Science Advances 08 Jan 2016: Vol. 2, no. 1, e DO: /sciadv

57 Polymer Origami Adv. Mater. 2015, 27, 79 85

58 Polymer Origami Adv. Mater. 2015, 27, 79 85

59 Getting Smarter 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