HYDROGEL: APPLICATIONS

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HYDROGEL APPLICATIONS

• Stimuli-responsive
• 1. Drug delivery
• Non-stimuli-responsive
• 1. Drug delivery
• - matrix or film/membrane for reservoir
  diffusion control
• Polaxamer (gels at 37 ?C) ? drug diffuses out
• - PEG or PEG-PPO based polymers are good
  carriers for drugs
• improve circulation time (prevent
  phagocytosis)
• 2. Wound dressing
• - temporary wound coverage skin
  substitutes
• 3. Hemocompatible (blood-compatible) surfaces
• 4. Soft contact lenses

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Hydrogels in Drug Delivery Why Useful

• High biocompatibility
• - increase circulation time
• - prevents the disruption of drug diffusion
  through hydrogel
• Matrix and reservoir systems can be prepared
• (1) Matrix drug uniformly distributed in
  highly crosslinked hydrogels
• (2) Reservoir drug/hydrogel core covered with
  water-insoluble membrane
• Controlled drug delivery by
• (1) diffusion delivery at controlled rates
  (non-responsive)
• (2) swelling/deswelling pulsatile/on-off
  control (stimuli-responsive)
• Stimuli-responsive hydrogels
• (1) temperature
• (2) pH
• (3) glucose

Uchegbu, I. Schatzlein, A.G. Polymers in Drug
Delviery (CRC Press)
3

• Wound dressing and temporary skin substitutes
• - hydrogels
• - note we will discuss skin TE (permanent skin
  substitutes) for Exam III
• 2 . Cardiovascular (blood-contacting) devices
• a. Polymers used
• b. Methods to improve blood-compatibility (i.e.
  hemocompatible, anti-fouling)
• - Hydrogels
• 3. Opthalmic devices
• a. Intraocular lenses
• b. Soft contact lenses hydrogels

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WOUND DRESSING AND TEMPORARY SKIN REPLACEMENTS
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SKIN Largest Organ of the Body

• Epidmermis outermost layer
• Composed of stratified squamous epithelium
  (layered, side-by-side dead cells)
• - cells (a)
  , (b) , and (c)
• contains some nerve cells, no blood vessels
• Dermis
• dense connective tissue (collagen), blood
  vessels, nerves, fibroblast cells
• Hypodermis
• adipose (fat) tissue looser connective tissue
  containing adipocytes

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INJURIES TO THE SKIN INVOLVING SKIN LOSS

• I. Sudden
• (a) Fire
• - Types of burns

1st Degree
2nd Degree
3rd Degree
(The body can regenerate epidermis, not dermis)
Equivalent to full thickness wound
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• (b) Wound
• -physical trauma wherein the skin is torn, cut or
  punctured (an open wound)
• Partial thickness wound through epidermis and
  into dermis
• Full thickness wound through dermis
• II. Chronic
• (a) Ulcers
• - Diabetic foot ulcer
• - Pressure ulcers

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Why Loss of Skin is Life-Threatening Skin is a
barrier to infection ? sepsis massive
infection infection in the bloodstream Skin is
a barrier to loss of water or electrolytes ?
shock body tissues do not get enough blood (due
to capillary
damage)

• Burns
• 2.2 million (USA annually)
• 150,000 hospitalized
• 10,000 die
• Diabetic foot ulcers
• - occurs in 15 of diabetics
• - most common foot injury leading to amputation

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WOUND DRESSING/COVERAGE and TEMPORARY SKIN
SUBSITUTES

• Role of Wound Dressing
• (a) stop bleeding and ease pain
• (b) adsorb exudates (fluids from wound)
• (c) facilitate epidermal ( dermal) resurfacing
• Moist wound healing
• - keeping wound moist increases rate of healing
  by up to 40
• - prompted the use of hydrogels

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Temporary Wound Coverage and Skin Substitutes

• Auto same patient
• transplant a partial thickness skin graft from
  part of non-injured area from the patient
• 0.3 to 0.5 mm thick
• include
• - harvest with an electric dermatome
• - place graft on wound
• - vascularization occurs within 3 days
• - graft may be meshed to make many small linear
  incisions allows the
• graft to spread and expand in size allows
  drainage of fluids from wound

Ratner, Biomaterials Science An Introduction to
Materials in Medicine, Chpt. 7
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Temporary Wound Coverage and Skin Substitutes
2. allo another patient tissue
vascularizes temporary closure of wound
re-epithelialization of wound site eventually
recognized as foreign to the host (patient)
reject so, must replace with an autograft 3.
Apligraf (E. Bell, 1981) Cultured
allogenic fibroblasts (dermis) mixed with bovine
collagen Type I Gel the solution
Surface of gel seeded with cultured allogenic
keratinocytes (epidermis) Expose to air ?
keratinocytes stratify like epidermis
Ratner, Biomaterials Science An Introduction to
Materials in Medicine, Chpt. 7
12
Apligraf
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Temporary Wound Coverage and Skin Substitutes
4. Xeno different species usually pig
(porcine) temporary wound closure and pain
reduction lower success than with cadaver
allograft 5. (a) A monolayer semi-permeable
membrane dressing to provide water and
bacterial barrier and control pain while
underlying wound heals. Biobrane

• Silicone Rubber/Elastomer
• Barrier to water loss, microbial
• invasion
• Nylon Fabric
• -partially crosslinked with porcine
• collagen Type 1- collagen peptides help adhere
  to
• wound
• Permeable (due to some porosity)
• to antibiotics, lets exudates out
• Leave on for 1 month

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Biobrane Removal
Biobrane Application

• Wound visualization
• Quick and easy application
• Reduced time to wound healing
• Cost savings when compared with comparable
  treatments
• Silicone barrier decreases the risk of infection

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Temporary Wound Coverage and Skin Substitutes

• 5.
• (b) Hydrogel with/without water-proof barrier
• (i) Water-proof barrier silicone,
  polyurethane (PU), PE
• (ii) Hydrogel PVOH, PHEMA, PEG and collagen
  (natural polymer)
• Hydron Burn Bandage PHEMA gel and linear
  PEG liquid
• Vigilon PEO crosslinked by radiation with
  PE outer layer

Keeps wound hydrated to accelerate healing.
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CARDIOVASCULAR (BLOOD-CONTACTING) DEVICES
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Blood-Contacting Devices
Stents
Arteriovenous (AV) Grafts
Vascular Grafts
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POLYMERS FOR CARDIOVASCULAR DEVICES

• Vascular Graft
• tube which replaces/bypasses part of a vessel
  (usually an artery) when it is
• restricted/weakened due to disease or injury.

Manufactured by weaving or knitting multifilament
texturized polymeric yarns.
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POLYMERS FOR CARDIOVASCULAR DEVICES
a. Dacron Graft Poly(ethylene terephthalate)
(PET)
Woven
Knitted
Fewer leaks More rigid, difficult to
handle In-growth of new tissue prevented
First infuse with patients blood More compliant
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POLYMERS FOR CARDIOVASCULAR DEVICES
b. GORE-TEX Graft ePTFE (expanded
poly(tetrafluoroethylene)
PTFE is rapidly stretch to create a strong
microporous material known as expanded PTFE, or
ePTFE.
Woven ePTFE fibers
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POLYMERS FOR CARDIOVASCULAR DEVICES

• Mechanical Heart Valve direct and regulate
  blood flow

Pyrolytic carbon
St. Jude Medical bileaflet tilting disk heart
valve
Dacron or GORE-TEX sewing cuff
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HEMOCOMPATIBILITY
thrombus formation at surface

• Thus, many blood-contacting devices rely on
  anticoagulants (heparin) and anti-platelet
  (Plavix) drugs (, side effects)

• Hemocompatible
• - Property of a material which does not cause
  formation of thrombosis (clot)
• clot-resistant or thrombo-resistant
• blood-compatible
• (Also, does not change blood function or
  transform components such as proteins).
• Extremely important in blood-contacting
  materials
• ? Thrombosis may compromise device function or
  cause fatal embolism

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Biomaterials with Insufficient Blood
Compatibility

• Polymers with suitable bulk properties often lack
  blood compatibility

Plasma air

• Silicones (PDMS)
• Poly(ethylene) (PE)
• Poly(propylene) (PP)
• Poly(ethylene terephthalate) (PET)
• Poly(tetrafluoroethylene) (PTFE)

Untreated PE (hydrophobic) Surface

• Attributed to their extreme
• Hydrophilizing the surface can improve resistance
  to blood protein and platelet adhesion.

Exposed first to blood proteins
J.H. Lee and H.B. Lee J. Biomed. Mater. Res. 1998
41, 304-311
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Blood

• 55-65 plasma
• - 93-94 H2O
• - 6-7 plasma proteins
• and salts - albumins (60)
• - globulins (35)
• - fibrinogen (4)
• - regulatory (1)
• 35-45 cells- red blood cells
• - white blood cells
• - platelets

Photographers Bruce Wetzel/Harry Schaefer,
National Cancer Institute
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Surface Induced Thrombosis
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Approaches to Reduce Protein Adhesion Improve
Hemocompatibility

• PEO
• Exceptional resistance to non-specific protein
  adhesion
• Stealth
• Ways PEO can be introduced/used

Surface-grafting
Physisorption
PEO-DA

A macromer with PEO and another segment
Crosslink to form coating
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Explaining the protein resistance of PEO

• Water H-bonding produces a local tetrahedral
  geometry around oxygen.
• PEO chains are able to fit into the tetrahedral
  geometry without lattice distortion.
• PEO chains are well- hydrated

Hydrophilic (PEO)
?static 30 ?
Hydrophobic (silicone)



PEO



?static 115 ?


Elbert, D.L. Hubbel, J.A. Annu. Rev. Mater. Sci.
1996, 26, 365-394 Gombotz, W.R. Guanghui, W.
Horbett, T.A. Hoffman, A.S. J. Biomed. Mater.
Res. 1991, 25, 1547-1562.
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Explaining the protein resistance of PEO

• The flexibility of PEO backbone produces high
  configurational mobility.
• PEO rotate freely to acquire many conformations.
• Steric repulsion of proteins
• Large excluded volume
• Blockage of underlying adsorption sites
• Entropic penalty would occur with protein
  adsorption

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Approaches to Reduce Protein Adhesion Improve
Hemocompatibility

• 2.
• Hydrated surfaces (very hydrophilic) prevent
  protein adhesion
• PEO, PVOH, PHEMA, etc.
• Theoretically, a thin layer of protein adsorbs
  but not a thrombus
• If albumins preferentially adsorb as thin layer,
  it can prevent thrombus
• Fluoro-polymers (PTFE), polysiloxanes
• In general, hydrophobic surfaces have poor
  hemocompatibility
• Plasma treatment with air or oxygen will create
  surface -OHs
• Surface-graft hydrophilic polymer
• Block copolymers (or blends) which arrange in
  hydrophilic and hydrophobic (nano)domains
• Methacryloyl oxyethylphosphorylcholine (MCP)

MCP
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OPTHALMIC DEVICES
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POLYMERS IN OPHTHALMICS

• Intraocular Lens replace opaque crystalline
  lens (cataract) of the eye

Foldable IOL
Inflexible IOL Tg 105 ?C Rigid Larger
incision needed
Silicone Acrylates MMA
PMMA
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POLYMERS IN OPHTHALMICS
2. Soft Contact Lenses placed on cornea to
correct vision
Hydrogels lightly crosslinked polymers which
absorb large quantities of water
Monomers used in the fabrication of contact lens
hydrogels
MCP
MMA
MAA
NVP
HEMA
Glycerol methacrylate (GMA)
EGDMA (crosslinker)
silicone-acrylate macromer (and others
previously mentioned)
(AIBN and BPO catalysts)
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• Silicone hydrogels are frequently used for
• Silicone hydrogels have good O2 permeability

Typical silicon-containing macromers for
synthesis of silicone hydrogels
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• Poly(hydroxyethylmethacrylate) (PHEMA)
• HEMA monomer EGDMA crosslinker
• 40 wt is water (increase water content
  increases O2 perm.)
• insufficient O2 permeability ?
• Silicone-Acrylates
• - PDMS-acrylate HEMA EGDMA
• - 20-30 wt water
• -

Impact of soft contact lens wear on the cornea.
The top row shows the consequences of low-O2
permeable lens wear (e.g. PHEMA (a) corneal
edema, (b) limbal redness, (c) vascular response,
(d) epithelial microcysts, and (e) endothelial
polymegethism. The bottom row shows the
corresponding benefits of high-O2 permeable
silicone acrylate hydrogel lens wear (a) no
corneal edema, (b) no increase in limbal redness,
(c) no blood vessels encroaching the cornea, (d)
few epithelial microcysts, and (e) no change in
number or size or corneal endothelial cells.