1. Hemodialysis Hollow Fiber Dialyzer Blood flows in and is cleaned
External procedure
3 sessions of 4 hrs a week
Filtration process only
Hollow Fiber Dialyzer
Blood flows in and is cleaned
using the process of diffusion
and ultrafiltration.
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2. Biocompatibility in Hemodialysis
Significant interaction of blood
Activation of humoral enzymatic pathways
Activation of white blood cells and platelets
Cuprophane membranes
Propose a biologically inspired design?
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3. Copyright © 1997 by Annual Reviews Inc. All rights reserved
Annu. Rev. Med :467–76
Copyright © 1997 by Annual Reviews Inc. All rights reserved
ACUTE RENAL FAILURE: Role of
Dialysis Membrane Biocompatibility
Manuel Pascual, MD, Rita D. Swinford, MD,1 and Nina Tolkoff-Rubin, MD
The Renal Unit and Transplantation Unit and 1 Pediatric Nephrology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
Hemodialysis Membranes: Interleukins, Biocompatibility, and
Middle Molecules
WALTER H. HORL
Department of Medicine, Division of Nephrology, University of Vienna, Vienna, Austria.
J Am Soc Nephrol 13: S62–S71, 2002
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4. Hydrogels
Frequently, presenters must deliver material of a technical nature to an audience unfamiliar with the topic or vocabulary. The material may be complex or heavy with detail. To present technical material effectively, use the following guidelines from Dale Carnegie Training®.
Consider the amount of time available and prepare to organize your material. Narrow your topic. Divide your presentation into clear segments. Follow a logical progression. Maintain your focus throughout. Close the presentation with a summary, repetition of the key steps, or a logical conclusion.
Keep your audience in mind at all times. For example, be sure data is clear and information is relevant. Keep the level of detail and vocabulary appropriate for the audience. Use visuals to support key points or steps. Keep alert to the needs of your listeners, and you will have a more receptive audience.
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5. Definition
-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
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6. The Cross-links may be physical or chemical:
by reaction of one or more monomers with pendant functional groups
hydrogen or ionic bonding, or
van der Waals interactions ++ __
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7. Hydrogels
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;
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8. Hydrogels: Swelling 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
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9. Hydrogels:
In a chemically cross-linked hydrogel, all of the polymer chains are connected by covalent bonds to form a network; and, thus
Can be viewed as one one molecule of large size or supramacromolecules;
The thermodynamically driven swelling force is counterbalanced by the retractive force of the crosslinked structure;
The unique property of these gels is there ability to maintain their original shape during and after swelling;
Two forces become equal at some point and equilibrium is reached
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11. Xerogels Dried hydrogels
Usually clear and swelling in water takes a long time;
The swelling behavior is due to slow diffusion of water through the compact polymer chains;
A useful property in controlled drug delivery;
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12. Chitosan
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13. Hydrogels: Swelling Why is the degree of swelling important?
solute diffusion coefficient through the hydrogel
surface properties and surface mobility
optical properties (particularly for contact lens applications)
mechanical properties
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14. Applications Pharmaceutical applications Methods for drug delivery
monomer composition and relative amounts of multi-polymer hydrogels can be varied to alter the diffusion characteristic and
permeability of the gel containing pharmaceutical agents
Methods for drug delivery
drug gets trapped in the hydrogel during polymerization
drug introduced during swelling in water
Release occurs by outflow of drug from the gel and inflow of water to the gel
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15. Drug delivery
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16. Examples of biological hydrogels:
Jello (a collagen gel ~ 97% water)
Extracellular matrix components
Polysaccharides
DNA/RNA
Blood clot
Mucin - lining the stomach, bronchial tubes, intestines
Gycocalyx - lining epithelial cells of blood vessels
Sinus secretions
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17. Fibrin Hydrogel (Blood Clot)
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18. Function of a biological hydrogel
Decreased permeability to large molecules
Structural strength (for epithelial cell walls)
Capture and clearance of foreign substances
Decreased resistance to sliding/gliding
High internal viscosity (low washout)
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19. Hydrogel Forming Polymers
Natural H O C H O N a O C 2 2 O O O H O H O O O H O O O H N H O H n n O p o l y ( h y a l u r o n i c a c i d ) p o l y ( s o d i u m a l g i n a t e )
Synthetic O n O O n O N H 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 ) p o l y ( e t h y l e n e g l y c o l )
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20. Hydrogels Highly swollen hydrogels: cellulose derivatives
poly(vinyl alcohol)
poly(N-vinyl 2-pyrrolidone), PNVP
poly(ethylene glycol)
Moderately or poorly swollen hydrogels:
poly(hydroxyethyl methacrylate), PHEMA and derivatives
One may copolymerize a higly hydrophilic
monomer with other less hydrophilic monomers to achieve desired swelling properties
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21. Hylauronic Acid
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22. Polyelectrolyte Hydrogels
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23. Polyelectrolyte Multilayers
Layer by layer deposition
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24. Alginate gels
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25. Alginate gels
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26. Enzyme Immobilization
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27. Cell Encapsulation
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30. Important features of hydrogels
Usually comprised of highly polyionic polymers
Often exhibit large volumetric changes eg. Highly compressed in secretory vessicle 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
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31. Hydrogel Forming Polymers
Natural
Synthetic
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32. Poly(methyl methacrylate)
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33. Acrylates
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34. Methacrylates
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35. How biological hydrogels grow
Polymerization/deposition
(blood clots)
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36. Hoffman, A. S. Adv. Drug Deliv. Rev., 2002, 43, 3
Preparation of Hydrogels
Hoffman, A. S. Adv. Drug Deliv. Rev., 2002, 43, 3
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37. Applications in Biomaterials and Tissue Engineering
Cell Encapsulation
Drug delivery
Surface modification
Enzyme Immobilization
Biosensors
Lab on a chip
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38. Hydrogels: PHEMA The most widely used hydrogel
water content similar to living tissues
inert to biological processes
shows resistance to degradation
permeable to metabolites
not absorbed by the body
withstands sterilization by heat
prepared in various shaped and forms
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39. Hydrogels: Applications
Biomedical use due to bio- and blood-compatibility
Pharmaceutical use due to hydrophilicity (controlled/sustained drug release)
Earliest biomedical application contact lenses
good mechanical stability
favorable refractive index
high oxygen permeability
needs hygienic maintenance
unable to correct for astigmatism
lubricating surface coating
used with catheters, drainage tubes and gloves
non-toxic
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40. Corning® Ultra Low Attachment Products Unique hydrogel surface inhibits cell attachment
                                                      
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41. Ocular Drug Delivery
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42. Applications artificial tendon and cartilage
wound healing dressings (Vigilon®, Hydron®,
Gelperm®)
non-antigenic, flexible wound cover
permeable to water and metabolites
low-strength
artificial kidney membranes
artificial skin
maxillofacial and sexual organ reconstruction materials
vocal cord replacement
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43. Applications Pharmaceutical applications Methods for drug delivery
monomer composition and relative amounts of multi-polymer hydrogels can be varied to alter the diffusion characteristic and
permeability of the gel containing pharmaceutical agents
Methods for drug delivery
drug gets trapped in the hydrogel during polymerization
drug introduced during swelling in water
Release occurs by outflow of drug from the gel and inflow of water to the gel
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46. Contact lens PMMA HEMA Fabrication methods
Computer assisted cutting (lathe)-PMMA rods
Spin casting-polymerization
Molding-polymerization
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