Transcript Document

Hemodialysis
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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Biocompatibility in
Hemodialysis
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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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Annu. Rev. Med. 1997. 48:467–76
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.
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J Am Soc Nephrol 13: S62–S71, 2002
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Hydrogels
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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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The Cross-links may be physical
or chemical:
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by reaction of one or
more monomers with
pendant functional
groups
hydrogen or ionic
bonding, or
van der Waals
interactions
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_
_
+
+
_
_
_
_
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Hydrogels
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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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Hydrogels: Swelling
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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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Hydrogels:
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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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Xerogels
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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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Chitosan
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Hydrogels: Swelling
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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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Applications
Pharmaceutical applications
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monomer composition and relative amounts of multipolymer hydrogels can be varied to alter the diffusion
characteristic and
permeability of the gel containing pharmaceutical agents
Methods for drug delivery
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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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Drug delivery
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Examples of biological
hydrogels:
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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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Fibrin Hydrogel (Blood Clot)
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Function of a biological hydrogel
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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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Hydrogel Forming Polymers
Natural
HO2C
HO
O HO
O
OH
HO
poly(hyaluronic acid)
NaO2C
O
NH
O
O
HO
O
OH
n
n
O
poly(sodium alginate)
Synthetic
O
n
O
n
poly(lactic acid)
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O
NH
poly(N-isopropyl acrylamide)
O
n
poly(ethylene glycol)
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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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Hylauronic Acid
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Polyelectrolyte Hydrogels
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Polyelectrolyte Multilayers
Layer by layer deposition
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Alginate gels
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Alginate gels
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Enzyme Immobilization
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Cell Encapsulation
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Important features of hydrogels
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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:
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repulsive electrostatic, hydrophobic
attractive, hydrogen binding, cross-linking
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Hydrogel Forming Polymers
Natural
HO2C
HO
O HO
O
OH
HO
poly(hyaluronic acid)
NaO2C
O
NH
O
O
HO
O
OH
n
n
O
poly(sodium alginate)
Synthetic
O
n
O
n
poly(lactic acid)
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O
NH
poly(N-isopropyl acrylamide)
O
n
poly(ethylene glycol)
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Poly(methyl methacrylate)
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Acrylates
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Methacrylates
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How biological hydrogels grow
•Polymerization/deposition
(blood clots)
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Preparation of Hydrogels
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Hoffman, A. S. Adv. Drug Deliv. Rev., 2002, 43, 3
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Applications in Biomaterials
and Tissue Engineering
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Cell Encapsulation
Drug delivery
Surface modification
Enzyme Immobilization
Biosensors
Lab on a chip
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Hydrogels: PHEMA
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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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Hydrogels: Applications
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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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Corning® Ultra Low Attachment Products
Unique hydrogel surface inhibits cell
attachment
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Ocular Drug Delivery
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Applications
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artificial tendon and cartilage
wound healing dressings (Vigilon®, Hydron®,
Gelperm®)
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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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Applications
Pharmaceutical applications
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monomer composition and relative amounts of multipolymer hydrogels can be varied to alter the diffusion
characteristic and
permeability of the gel containing pharmaceutical agents
Methods for drug delivery



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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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Contact lens
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PMMA
HEMA
Fabrication methods
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Computer assisted cutting (lathe)-PMMA rods
Spin casting-polymerization
Molding-polymerization
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