Hydrogels and Their Biomedical Uses. M. R. Naimi-Jamal

Transcription

1 Hydrogels and Their Biomedical Uses M. R. Naimi-Jamal

2 Overview Hydrogels Structure Swelling properties Biomedical Uses

3 Common Hydrogels? Can you think of hydrogels in your everyday life? - Contact Lenses - Jello (a collagen gel ~ 97% water) - Extracellular matrix components - Polysaccharides - DNA/RNA - Blood clot

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5 Applications of Hydrogels Soft contact lenses Pills/capsules Bioadhesive carriers Implant coatings Transdermal drug delivery Electrophoresis gels Wound healing Chromatographic packaging material

6 Hydrogels Hydrogels are water swollen, crosslinked polymeric structures produced by the simple reaction of one or more monomers or by association of bonds such as hydrogen bonds and strong van der Waals interactions between chains. -N. A. Peppas in Biomaterials Science (1996)

7 Other definitions Water insoluble, three dimensional network of polymeric chains that are crosslinked by chemical or physical bonding Polymers capable of swelling substantially in aqueous conditions (eg hydrophilic) Polymeric network in which water is dispersed throughout the structure 7

8 Behavior of Hydrogels No flow when in the steady-state By weight, gels are mostly liquid, yet they behave like solids They can absorb large quantities of water May absorb up to 1000 times their dry weight Cross linkers within the fluid give a gel its structure (hardness) and contribute to stickiness (tack).

9 Volume degree of swelling (Q) Q = actual sample volume in the swollen state volume in the dry state

10 Weight degree of swelling = actual sample weight in the swollen state weight in the dry state

11 Based on structural features, hydrogels can be classified as... Amorphous hydrogels Randomly arranged macromolecular chains Semicrystalline hydrogels Dense regions of ordered macromolecular chains (crystallites) Hydrogen bonded hydrogels 3-D network held together by hydrogen bonds Strong hydrophobic/hydrophillic interactions

12 Based on crosslinkers features, hydrogels can be classified as... Chemical Physical

13 Chemical Covalently crosslinked Absorb water until they reach equilibrium swelling (crosslink density dependent) High stability in harsh environments (high temp, acidic/basic and high stress)

14 Physical Non-covalently crosslinked Disordered networks are held together by associative forces capable of forming noncovalent crosslinks (molecular entanglements, electrostatic interactions, hydrogen bonding, and hydrophobic interactions) Weaker and more reversible forms of chainchain interaction Respond to physical changes (temperature, ph, ionic strength and stress)

15 Hydrogel Fabrication Chemical hydrogels Physical hydrogels Covalently crosslinked Noncovalently crosslinked Hydrogen bonding hydrophobic interaction crystallinity stereocomplex formation ionic complexation Thermoset hydrogels Thermoplastic hydrogels Reliable shape stability and memory Limited shape stability and memory

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17 Physical crosslinking Cross-linking without chemical reaction ionic interaction, hydrogen bonding, antigen-antibody interaction, supramolecular association Ionic hydrogel

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20 Chemical Hydrogels Methods Co-polymerization of monomer and crosslinker HEMA and EGDMA (Ethylene glycol dimethacrylate) Crosslinking water soluble polymers Conversion of hydrophobic polymers to hydrophilic polymers plus crosslinking

21 Hydrogel Fabrication Chemical crosslinking Polymerization of water soluble monomers in the presence of bi- or multifunctional cross-linking agent + Monomer Crosslinker Copolymerization Polymerization Hydrogel network Vinyl group-containing water-soluble polymers

22 EGDMA HEMA

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26 An example as Wound Dressing

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31 Based on ionic charges, hydrogels can be classified as... Neutral hydrogels No charge Anionic hydrogels Negatively charged Cationic hydrogels Positively charged Ampholytic hydrogels Capable of behaving either positively or negatively

32 Classes of Hydrogels

33 Hydrogel Forming Polymers Natural H O 2 C H O N a O 2 C O H O O O H O O O H O O O H N H O H n n p o l y ( h y a l u r o n i c a c i d ) O p o l y ( s o d i u m a l g i n a t e ) Synthetic O O n O n N H O n p o l y ( l a c t i c a c i d ) p o l y ( N - i s o p r o p y l a c r y l a m i d e ) poly ( e t h y l e n e g l y c o l )

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35 Hydrogel Swelling One or more highly electronegative atoms which results in charge asymmetry favoring hydrogen bonding with water Because of their hydrophilic nature dry materials absorb water By definition, water must constitute at least 10% of the total weight (or volume) for a materials to be a hydrogel When the content of water exceeds 95% of the total weight (or volume), the hydrogel is said to be superabsorbant 35

36 Important features of hydrogels Usually comprised of highly polyionic polymers Often exhibit large volumetric changes eg. highly compressed in secretory vesicle and expand rapidly and dramatically on release Can undergo volumetric phase transitions in response to ionic concentrations (Ca ++, H + ), temperature,... Volume is determined by combination of attractive and repulsive forces: repulsive electrostatic, hydrophobic attractive, hydrogen binding, cross-linking 36

37 Swelling...Thermodynamically Speaking Network starts to swell due to the thermodynamic compatibility of the polymer chains and water Swelling in chemical (crosslinked) polymers is dependent on the solvent Swelling force is counterbalanced by the retractive force induced by the crosslinks of the network Swelling equilibrium is reached when these two forces are equal Degree of swelling can be quantified by: ratio of sample volume in the swollen state to volume in the dry state weight degree of swelling: ratio of the weight of swollen sample to that of the dry sample

38 Swelling Properties Gibbs Free Energy G= G elastic + G mix Chemical Potential µ 1 -µ 1,0 = µ elastic + µ mix µ mix =RT(ln(1-2v 2,s )+v 2,s +χ 1 v^2 2,s ) G=Gibbs Free Energy work exchanged by the system with its surroundings minus the work of the pressure forces during a reversible transformation of the system from the same initial state to the same final state G<0 Spontaneous G=0 Equilibrium G>0 Non-spontaneous

39 Swelling Properties Gibbs Free Energy G= G elastic + G mix Chemical Potential µ 1 -µ 1,0 = µ elastic + µ mix µ mix =RT(ln(1-2v 2,s )+v 2,s +χ 1 v^2 2,s ) µ= Chemical G=Gibbs Potential Free Energy the chemical potential is the change work in exchanged a characteristic by the system with its surroundings minus the work of thermodynamic state function per the pressure forces during a change reversible in the transformation number of of the molecules system from the same initial state to the same final state Particles will tend to move from regions of G<0 high chemical Spontaneous potential to regions G=0 of low Equilibrium chemical potential G>0 Non-spontaneous

40 Swelling Properties Gibbs Free Energy G= G elastic + G mix Chemical Potential µ 1 -µ 1,0 = µ elastic + µ mix µ mix =RT(ln(1-2v 2,s )+v 2,s +χ 1 v^2 2,s ) v 2,s =polymer volume fraction of the gel v 2,s = Volume of polymer = v p = 1 Volume of swollen gel v gel Q Q= volume degree of swelling χ 1= polymer-water interaction parameter (look up in a table) R= Universal Gas Constant= (15) J K 1 mol 1

41 Some swollen Hydrogels Highly swollen hydrogels: cellulose derivatives poly(vinyl alcohol) poly(ethylene glycol) What do these all have in common? Lots of OH (or =O) groups to interact with acidic environments hydrophillic swelling Moderately or poorly swollen hydrogels: poly(hydroxyethyl methacrylate), PHEMA and derivatives One may copolymerize a highly hydrophilic monomer with other less hydrophilic monomers to achieve desired swelling properties 42

42 Contact Angle (wetability) Hydrophobic water hating Hydrophilic water loving Why is this important to materials selection? Do you want your eyes to be dried out by your contact lenses? Probably not * Cool fact, fluorinated surfaces have the most hydrophobic properties and are deemed super-hydrophobic.

43 Electrowetting of the surface Top: charge neutral (grounded) surface with high contact angle Bottom: Allowing voltage between the drop and the electrode changes the distribution of electric charge within the drop and significantly decreases the contact angle. The polarity of voltage in the drawing is arbitrary, and in both directions electrowetting will occur. In a natural environment, this may be electric charge change due to ph changes

44 Other Important Properties Solute diffusion coefficient through the hydrogel Optical properties Mechanical properties Hydrophilic hydrogel surfaces are poor substrates for Protein adsorption Cell adsorption

45 How biological hydrogels grow Polymerization/deposition (blood clots) 22-Apr-13 46

46 Environmentally Responsive Hydrogels Hydrogels that exhibit swelling changes due to the external ph Temperature Ionic Concentration

47 Environmentally Responsive Hydrogels ph Location in Body ph Gastric Contents 1.0 Urine Intracellular 6.8 Interstitial (also called extravascular compartment or tissue space) 7.0 Blood

48 Environmentally Responsive Hydrogels Temperature Location in Body Temperature C Normal Core 37 Deviations During Disease Normal Skin 28 Skin at Extremeties 0-45

49 Environmentally Responsive Hydrogels Ionic concentration Cations Sodium 142 Pottasium 4 Calcium 5 Magnesium 2 Concentration in Blood (meq/l) Anions Chlorine 101 Bicarbonate 27 Phosphate 2 Sulfate 1 Proteins 22 Concentration in Blood (meq/l) Notice they both add up to the same equillibrium

50 Hydrogel Advantages Non-thrombogenic Non-ionic hydrogels used for blood contacting applications Heparinized hydrogels show promise Biocompatible Good transport of nutrients to cells and products from cells May be easily modified with cell adhesion ligands Can be injected in vivo as a liquid that gels at body temperature

51 Advantages of Hydrogels Environment can protect cells and other substances (i.e. drugs, proteins, and peptides) Timed release of growth factors and other nutrients to ensure proper tissue growth Good transport properties Easy to modify

52 Disadvantages of Hydrogels Low mechanical strength Hard to handle Difficult to load difficult to be sterilized

53 Types of Hydrogels Natural Polymers Dextran, Chitosan, Collagen, Dextran Sulfate Advantages Generally have high biocompatibility Intrinsic cellular interactions Biodegradable Cell controlled degradability Low toxicity byproducts Disadvantages Mechanical Strength Batch variation Animal derived materials may pass on viruses

54 Types of Hydrogels Synthetic Polymers PEG-PLA-PEG, Poly (vinyl alcohol) Advantages Precise control and mass produced Can be tailored to give a wide range of properties (can be designed to meet specific needs) Low immunogenecity Minimize risk of biological pathogens or contaminants Disadvantages Low biodegradability Can include toxic substances Combination of natural and synthetic Collagen-acrylate, P (PEG-co-peptides)

55 Properties of Hydrogels Pore Size Fabrication techniques Shape and surface/volume ratio H 2 O content Strength Swelling activation

56 Why Hydrogels? Tissue Engineering Scaffolds for tissue engineering Cell Culture Systems Drug Delivery Time released delivery Contact Lenses

57 Biomedical Uses for Hydrogels Common Scaffolds in tissue engineering. Sustained-release delivery systems Hydrogels that are responsive to specific molecules, such as glucose or antigens can be used as biosensors. Disposable diapers where they "capture" urine, or in sanitary napkins Contact lenses (silicone hydrogels, polyacrylamides) Medical electrodes using hydrogels composed of cross linked polymers (PEO, polyamps and polyvinylpyrrolidone) Lubricating surface coating used with catheters, drainage tubes and gloves

58 Biomedical Uses for Hydrogels Less common uses include Breast implants Dressings for healing of burn or other hard-to-heal wounds. Wound gels are excellent for helping to create or maintain a moist environment. Reservoirs in topical drug delivery; particularly ionic drugs Artificial tendon and cartilage Wound healing dressings (Vigilon, Hydron, Gelperm ) non-antigenic, flexible wound cover permeable to water and metabolites Artificial kidney membranes Artificial skin Maxillofacial and sexual organ reconstruction materials Vocal cord replacement Butt injections 59

59 Headlines

60 Ref.: Smart Polymers: Hydrogels and Shape Memory Polymers Dr. Jenny Amos February 19, 2009