polymers used for eye implants and tissue adhesives

1. MARY MINCY
II MSc BPS

3. INTRODUCTION
 There are 60 billion
people in the world who
are blind or facing
blindness due to disease
of the retina
,cornea,…and there’s
little that can done for
them.
 For the vast majority
,their best hope is
through prosthetic
devices

4. How The Eye Works
 Light is focused primarily by
the cornea
 The iris controlling the amount
of light reaching the back of the
eye
 The eye's crystalline lens is
located directly behind the pupil
and further focuses light.
 Then light reaches the retina
;The retina contains photo
receptors that detect light.
These photo receptors are
known as cones and rods. The
retina contains nerve cells that
transmit signals from the retina
to the brain.

5. EYE IMPLANT
 Eye implant are used to restore functionality of cornea,
lens,vitreous humor etc. when they are damaged or
diseased.
Device Medical application
Contact lens Correct vision
Intraocular lens Replace lens containing cataracts
Epikeratoplasty Change corneal curvature & correct
vision
Scleral buckling materials Indent detached retina
Viscous polymer solutions Insertion in Intraocular lens, cataract
removal &maintain retinal position

6. 1) CORNEAL IMPLANTS
The cornea is an avascular tissue that
consists of three principal layers
1. The outer most layer is the
epithelium
2. Central and main portion of the
cornea is stroma,a collagenous
connective tissue that is 78%
hydrated in its normal state
3. The endothelium is the inner most
nanocellular layer is mostly
responsible for maintaining
normal corneal hydration
 Swelling, tissue proliferation,
&vascularization may compromise the
transparency of cornea
 There are several types of corneal
Implants, that replace all or part of
cornea
Corneal layers

7. a) Epikeratophakia & Artificial
epithelium
 An epithelium that has become irregular through
swelling and proliferation has been replaced by an
artificial epithelium
 It is made of hard plastic contact lens glued with
cyanoacrylate adhesive to the corneal stroma
 This procedure has not been successful mainly
because of failure of the glue to maintain a tight
attachment of the prosthesis to the corneal stroma

8. b. Artificial cornea
 Corneal transplants from donar eyes are usually highly
successful
 The eye should be harvested from cadaver within 1 hr
of death
 The whole eye is generally preserved in sterile liquid
paraffin at a temperature 3-5°C
 Graft is cut from it at the time of use

9. c.Artificial Endothelium
 The corneal endothelium has been replaced, but not
very successfully in the long term, by a silicone rubber
membrane that passively controls corneal hydration

10. 3) INTRAOCULAR LENS IMPLANTS
 Intraocular lenses (IOLs) are used after cataract
extraction to replace the opaque crystalline lens of the
eye
 The requirements of IOL material are good optical
properties and biocompatibility with the surrounding
tissues
 Most IOL are made of PMMA and the haptics are often
made of the same material or pp fiber

11. 4. IMPLANTS FOR RETINAL
DETACHMENT SURGERY
Vitreous implants
Injectable synthetic polymers are used with increasing
frequency
Sodium hyaluronate solutions are useful in some of
these cases
Alternatively high viscosity silicone oil,usually,poly
dimethyl siloxane is injected into the vitreous cavity
This procedure is still controversial due to reported
complications such as oik emulsification in the
anterior chamber

12.  Scleral buckling materials
It must be soft and elastic
Materials used; silicone sponges solid silicone rubber
and copolymer of 2-hydroxyethyl acrylate with methyl
acrylate

13. 5. Surgical Adhesive
 The cyanoacrylate adhesives are used as temporary
dressing over corneal ulcers and wounds
 Cyanoacrylate surgical adhesives, the monomers arw
applied directly to the tissues and almost
instantaneously polymerize and adhere to the tissues

14. 6. Eye Shields
 These are used in the treatment of basement
membrane
 Once applied to eye these shield absorb fluid from
ocular surface and begin to dissolve
 The polymers in use are hydrogels,polyvinyl
alcohol,silicone rubber and collagen
6. Eye Shields

15. 7.Artificial Tears
 Keratoconjunctivitis sicca is a dry eye syndrome
characterised by either decreased tear formation
 Tear substitutes commonly employed contain
methylcellulose, polyvinyl alcohol,hyaluronic and/ or
chondrotin sulfate

16. 8.CONTACT LENS

17. CONTACT LENS
 A contact lens is a prescription medical device
manufactured from high-grade plastic polymers.
 The contact lens rests on the front surface of the eye
(the cornea) and works just like eyeglasses – it bends
light rays so that images are properly focused on the
retina (at the back of the eye).
 Contact lenses can be worn by people with eye
disorders as an alternative to glasses.

18. What Makes a Good Contact Lens,
and Biocompatibility?
 Several things must be considered when designing contact lenses, but
perhaps the most important is biocompatibility.
 Another most important is the wettability of the lens.
 Contact lens surface must be made hydrophilic.
 The surface must resist the formation of a biofilm it must also be semi-
permeable.
 The polymer that makes up the lens is important it is also important,
for it to be produced in a way so that there is no contamination to the
eye.
 It is important to test the monomers for biocompatibility, and to assure
that the monomers used in the lens are highly pure.
 A big requirement of the lens is that it must be lightweight.
 The lens must also be strong to avoid tearing and/or scratching, have a
reasonably high modulus of elasticity for ease of handling, and yet still
soft and flexible enough to feel comfortable on the eye.
 Finally a good contact lens must be affordable price.

19. What properties are desirable in polymers
for contact lenses?
The properties of an ideal polymer for contact lenses include:
 _ Transparent
 _ Some flexibility
 _ Low density
 _ Tough
 _ Unreactive to chemicals on the eye surface
 _ Easy to manufacture
 _ Made from a raw material that is available in abundance
 _ Easy to mould
 _ Refractive index suitable for bending light rays
 _ Hydrophilic (‘water-loving’)
 _ Lets oxygen gas pass through to the eye surface
 _ Produces lenses that are easy to insert, remove, clean and store.

20. Hard Contact Lenses
 Currently fifteen percent of the thirty million contact
lens users wear what is known as hard contact lenses. 4
 Hard contacts consist of polymers that are below their
glass transition temperature, and typically contain little
or no water.
 There are several kinds of hard contact lenses, the most
common are the rigid gas permeable (RGP) ) lens, and
silicone acrylate based lenses.
 The lenses are typically very stiff and have a high
modulus of elasticity. This gives them a high tear
strength, and makes them very easy to handle.

21. PMMA
 PMMA is an ideal polymer to be used for hard contact
lenses because it is cheap and easy to make.
 It is moderately hydrophobic, which also contributes
to it repelling proteins effectively.
 The lenses do not allow oxygen to pass directly to the
cornea, which can be damaging to the eye.
 Users have to put a wetting solution in their eyes
before putting the lenses in.
 This impermeability is what restricts PMMA lenses
from being used more then about 8 hours at a time.

22.  The impermeability of PMMA lenses could be overcome
by copolymerizing MMA with silicone acrylate.
 The result was a polymer that had the strength of MMA,
but also the oxygen permeability of silicone.
 Silicone is hydrophobic however, so the wetting agent
methacrylic acid (MAA) was added to increase lens
wetability.
 While hard contacts are not the most convenient they
are very cost effective
 Hard lenses are also very durable, and their strength
helps them resist scratching, and protect the cornea.

23. Soft Contact Lenses
 The most popular type of contact lens is a soft lens.
 Soft contact lenses are made of thermo-set polymer hydrogels.
 Like hard contacts lens polymers, these gels are made up of a
three dimensional, amorphous network with cross-links.
 The lenses are soft because the polymer is above its glass
transition temperature.
 Soft contacts are typically formed using cast molding or the spin
cast method.
 In soft contact lenses the water content affect many things. The
permeability of the lens is proportional to the amount of water
in the lens
 The first hydrogel contacts consisted of HEMA that was cross-
linked with either ethylene dimethacrylate (EDMA) or ethylene
glycol monogethacrylate (EGDMA).

24. Polyacrylamide.
 The first soft contact lenses were introduced in 1971.
 These were made from a polymer called polyacrylamide.
 This polymer is different from PMMA because it
contains nitrogen atoms in its structure (PMMA does
not contain nitrogen).
 Polyacrylamide is similar to the polymers used to make
acrylic fibres for fabrics.
 When the polyacrylamide chains are cross-linked, the
material absorbs water. Substances such as this are called
hydrophilic (‘water-loving’).

25.  This property makes polyacrylamide a useful material
for producing contact lenses.
 Between 38% and 79% of a soft contact lens is water.
 This water keeps the lens soft and flexible.
 However, the high water content also makes the lens
more fragile and reduces clarity of vision.
 Soft lenses are cheaper than hard lenses and this has
added to their popularity.
 In fact, some soft lenses can be used for one day and
then discarded.

26. Rigid Gas Permeable Lenses
 In 1979, the first rigid gas-permeable lenses (also known as
RGPs) became available.
 These lenses are made from a combination of PMMA, silicones
and fluoropolymers.
 This combination allows oxygen to pass directly through the lens
to the eye, which makes the lens more comfortable for the
wearer.
 It may only take three hours to get used to wearing this kind of
lens.
 The rigidity of RGPs can also make vision clearer than with soft
lenses.
 RGPs are better suited to correcting astigmatism and for bifocal
needs than the other kinds of lenses.
 The disadvantages of RGPS include their high cost and some
inflexibility in the lens.

28. • Tissue adhesives are substances that
hold tissues together, and could be
broadly applicable in medicine and
surgery.
• In appropriate circumstances, such
materials could be attractive alternatives
to sutures and staples since they can be
applied more quickly, causes less pain
and may require less equipment.
• In addition, there is no risk to the
practitioner from sharp instruments.

29. HOW IT FUNCTIONS?
 Tissue adhesives hold tissues together (glues) but also
can serve as barriers to leakage when used for wound
closure.
 Consequently the causes of glue failure can include:
1. adhesive failure—where the material detaches from
the tissue
2. cohesive failure—where the adhesive fails within itself.
Even if the glue functions well, the tissue itself may
tear; this may occur when both adhesive and cohesive
forces are too strong.

30.  Tissue adhesives can be divided into three main chemical
categories:
1. Cyanoacrylates
2. fibrin sealant,
3. other cross-linkable polymers.
 Cyanoacrylates are the strongest and are widely used for
wound closure.
 Fibrin based materials, being weaker are applied as a
sealant in many surgical procedures in conjunction with
suturing.
 Hydrogels, collagen compounds, peptides and polyethylene
glycol (PEGs)-based materials are also considered weak
and are therefore used as topical wound dressings or as
sealants where mechanical properties are of less.

32. CYANOACRYLATES
 Cyanoacrylates were first synthesized in 1949 and were
first reported as tissue adhesives ten years later .
 They are produced synthetically by condensation
between cyanoacetic acid and a suitable alcohol.
 The cyanoacetate oil formed is reacted with
paraformaldehyde to form cyanoacrylate oligomers.
 High vacuum (*0.7 mm Hg) and heat (150–180C) are
applied and depolymerization is carried out to produce
clear and colorless liquids monomers.
 Usually, further purification by repeated vacuum
distillations is utilized to get a medical grade material .

33.  Although cyanoacrylates are considered very strong and
effective, their use— particularly within tissues—is limited by
tissue toxicity, including necrosis, which occurs in the
immediate vicinity of the cyanoacrylates.
 The toxicity of cyanoacrylate glues has been attributed to several
factors including:
1. direct toxicity of monomers such as methyl-2-cyanoacrylate or
of byproducts such as cyanoacetate and formaldehyde
2. insufficient tissue vascularization
3. the heat from the exothermic nature of the reaction.
 A second concern limiting the use of cyanoacrylates in tissues
stems from the fact that they are hard and brittle, hence they
may have insufficient flexibility for the dynamic nature of in vivo
conditions.
 As a result, cyanoacrylates are currently limited to external or
temporary applications.

34. WHERE IT USES?
 Cyanoacrylate tissue glues have found multiple uses.
They have been used in the management of corneal
perforations, corneal melts and wound leaks.
 The cornea glue may also improve visual outcomes
by obviating the need for sutures, which are
associated with inducing astigmatism.
 In addition, they may create a more watertight seal,
decreasing the risk of infection, thus reducing the
chance of devastating intraocular infections such as
endophthalmitis.

35. Fibrin Glue/Sealant
 Fibrin tissue glue was first introduced in 1909 as an hemostatic
agent, and was first used as an adhesive material in 1940 .
 Fibrin based tissue adhesives are composed of purified fibrinogen
and thrombin, and form a bond via the physiological cascade of
coagulation .
 Since fibrin tissue adhesives are prepared from pooled human
blood, there has been concern for potential viral transmission, in
particular of hepatitis and human immunodeficiency virus (HIV) .
 Nowadays, these products are carefully screened so that the risk of
viral transmission is considered minuscule compared to the risk
with other biomaterials taken from donors.
 Although fibrin glues are considered less toxic than cyanoacrylates
their low adhesive strength limits their use in many surgical
procedures.

36. Formation of cross-linked fibrin
from fibrinogen

37. WHERE IT USES?
 It has been used clinically in many settings including:
1. Anal fistulae closure to preserve sphincter function
2. prevention of esophageal leakage and stricture after
esophageal reconstruction from caustic injury ,
3. prevention of cerebral spinal fluid leakage after
durotomy during lumbar spinal surgery ,
4. hernia repairs ,
5. posterolateral spinal fusions , nerve anastomoses & in
cardiovascular surgeries .

38. Other In Situ Cross-linking
Polymers
 Water soluble polymers forming a three dimensional
(3D) network at the site of injection have been used as
tissue adhesives due to their safety, mechanical
properties and ease of application.
 Cross-linking prevents early dissolution of the material
in the body, and maintains cohesive integrity.
 Since it may be desirable that tissue adhesives degrade
after healing has occurred, these compounds will
frequently contain labile bonds in their backbone or in
the cross-linking domains.

39.  Several polymers, synthetic and natural, have been
proposed for tissue adhesion, including :
1. poly(ethylene glycol) (PEG) ,
2. chitosan
3. laser- and non-laser-activated protein solders
4. porcine gelatin
5. glutaraldehyde mixed with collagen
 Adhesive forces between the gel and the tissue can be
due to
1. covalent bonds formed between functional groups
on one of the polymers (e.g. aldehyde)
2. weak van der Waals or hydrogen
 bonds interactions (e.g. PEG compounds).

40. Available adhesives of cross-linking polymers in
market
 BioGlue (Cryolife, Kennesaw, GA) is a surgical adhesive
used in cardiovascular surgery, approved by the FDA and
the EU as an adjunct in human vascular and pulmonary
repair surgery .
 It is composed of purified bovine serum albumin (BSA)
and glutaraldehyde.
 Another two-component system is made of aminated
star-PEG (a starshaped poly[ethylene glycol]) and high-
molecular-weight dextran-aldehyde.
 PEG-based sealants have gained interest in recent years
because they are considered safe, easy to apply, and very
effective in sealing suture lines when cross-linked .

41.  However, the adhesive strength of these biomaterials
have not shown higher adhesive strength than that
of fibrin sealant .
 This is believed to be the result of two major factors:
1. low adhesion forces due to intra- and/or
intermolecular cross-linking reactions rather than
with the surrounding tissue
2. the soft, flexible nature of hydrogel networks that
limits the cohesion forces within the material.

42. Tissue Adhesives Releasing Drugs
 Tissue adhesives, in addition to being utilized as
glues or sealants, can be used as drug delivery
systems.
 The architecture of the material can be engineered
to release its contents in the desired pattern directly
to the target site.
 Local release by the glue enables the administration
of controlled dosages, reducing the risk of adverse
drug effects.