Hemodialysis

External procedure 3 sessions of 4 hrs a week Filtration process only

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?

Hollow Fiber Dialyzer Blood flows in and is cleaned using the process of diffusion and ultrafiltration.

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Annu. Rev. Med. 1997. 48:46776 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, M S h l B Massachusetts 02114 h

Hydrogels

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: S62S71, 2002

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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) ( g y p ) -polymeric network in which water is dispersed throughout the structure

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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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; t 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
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:
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
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;

Chitosan

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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) li ti ) mechanical properties

Applications
Pharmaceutical applications
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

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

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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Fibrin Hydrogel (Blood Clot)

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 gg g High internal viscosity (low washout)

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Hydrogel Forming Polymers

Natural
HO2C HO O HO O OH HO O NH O O n poly(sodium alginate) NaO2C HO OH O O n

Hydrogels
Highly swollen hydrogels: cellulose derivatives poly(vinyl alcohol) p y( poly(N-vinyl 2-pyrrolidone), PNVP y py ) 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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poly(hyaluronic acid)

Synthetic
O O n O n NH O n

poly(lactic acid)
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poly(N-isopropyl acrylamide)

poly(ethylene glycol)

Hylauronic Acid

Polyelectrolyte Hydrogels

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Polyelectrolyte Multilayers
Layer by layer deposition

Alginate gels

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Alginate gels

Enzyme Immobilization

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Cell Encapsulation

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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 d C undergo volumetric phase t l ti h transitions i iti 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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Hydrogel Forming Polymers

Natural
HO2C HO O HO O OH HO O NH O O n poly(sodium alginate) NaO2C HO OH O O n

Poly(methyl methacrylate)

poly(hyaluronic acid)

Synthetic
O O n O n NH O n

poly(lactic acid)
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poly(N-isopropyl acrylamide)

poly(ethylene glycol)
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Acrylates

Methacrylates

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Preparation of Hydrogels
How biological hydrogels grow

Polymerization/deposition (blood clots)

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Hoffman, A. S. Adv. Drug Deliv. Rev., 2002, 43, 3

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Applications in Biomaterials and Tissue Engineering

Cell Encapsulation Drug delivery Surface modification Enzyme Immobilization Biosensors Lab on a chip

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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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

Corning Ultra Low Attachment Products Unique hydrogel surface inhibits cell attachment

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Ocular Drug Delivery

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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Applications
Pharmaceutical applications
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

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
PMMA HEMA Fabrication methods
Computer assisted cutting (lathe)-PMMA rods Spin casting-polymerization Molding-polymerization

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