Medical Adhesives

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Dr. M. R. Naimi-Jamal Department of Chemsitry, IUST

Adhesion

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Definition: The state at which two surfaces are held together by interfacial forces, which may consist of all known chemical attractive forces, as well as mechanical interlocking action or both.

Adhesive

A substance capable of holding materials together in a functional manner by surface attachment (performance). A general term that includes cement, glue, mucilage and paste.

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Sealant

A material applied to a joint in paste or liquid form that hardens or cures in place, forming a barrier against gas or liquid entry.

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Adhesives and Sealants-Biomaterials?

Join components of medical devices-Mechanical fastening;

Prevent corrosion; Resist fatigue; Fill space – smooth contours-joining

prosthesis to bone; Wound sealing & closure

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Adhesive Materials can be classified in a number of ways:

Natural or synthetic polymer base; Thermoplastic or thermosets; Physical form (one or multiple component,

films, etc) Functional type (structural, hot melt, pressure

sensitive); Chemical families (epoxy, silicone, etc.)

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General Considerations in the Application of Adhesive Bonding

When applied, adhesives have to 'wet' the surface; If the adhesive does not wet the substrate well, poor

adhesion is likely to be a result; They need to be mobile and flow into all the tiny

nooks and crannies of the substrate; Once good wetting takes place, an adhesive needs

to become solid and not flow at all. This is called setting or curing (polymerization).

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Adhesive Joint Breaking strength is determined by: Mechanical properties of the materials of the

joint; The extent of the interfacial contact (number,

extent, type and distribution of voids); Presence of internal stresses; The joint geometry; and, The details of mechanical loading.

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Bonding Mechanisms Mechanical Interlocking; Formation of covalent bonds across the

interface; Electrostatic Attraction-dominant Forces are not significant beyond 0.5 nm-

therefore contact is necessary

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Surface Treatment No treatment (low cost, but poor reproducibility); Solvent wiping; Vapor degreasing; Mechanical abrasion; Plasma treatment; Etching; Chemical deposition-primers, organosilanes

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Benefits of Adhesives

Joins dissimilar materials Even stress distribution Fills large gaps Seals and bonds Easily automated Aesthetically acceptable

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Limitations of Adhesives

Requires cure Requires fixture time Can be messy Requires chemicals in plant

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Adhesives are Polymers Thermoplastics Thermosets

Available as solids, liquids and pastes and most

can be supported by films of various thickness.

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Some adhesives Acrylics Epoxies Polyurethanes Silicones

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Adhesives for medical applications

The use of surgical tissue adhesives in medicine has developed more than 50 years ago

Traditionally, the area of tissue reattachment or repair following surgery has been dominated by sutures, staples and wiring

Recently, there is a huge potential for tissue adhesives in clinical practice

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Pressure Sensitive Adhesives (PSAs) PSAs have been used for adhering wound

dressing to skin PSAs have Tg in the range of -20 to -60ºC,

which means they are soft materials at room temp.

These soft polymers are able to flow and wet out on to a surface and are able to adherence to that surface

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Pressure Sensitive Adhesives (PSAs) The bond formed between PSA and substrate is

not permenant and can be broken with a measurable force

Mid 19th century, the first adhesive plasters were used, the first aid application of dressing become more demanding, and undergone significant development

Early adhesive formulations were based on blends of natural rubber and resin.

Now PSAs were dominated by acrylic copolymer

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Example of First Aid Dressing Arcylics on PET

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Requirement for PSAs 1) Should be permanently and aggressively tacky,

adhere with only slight finger pressure 2) Form a strong bond with surfaces 3) Sufficient cohesiveness that it can be removed

without leaving a residue 4) Need to be chemically and biologically

accepted to the skin -no irritation or sensitization-

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Requirement for PSAs

5) Adhesives must have sufficient flow to ensure intimate surface contact

6) Must be able to cope with moisture at the skin without compromising performance

7) PSAs should be easily removed with minimal trauma to the skin

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Pressure-Sensitive Adhesives Applications

Labels: many medical devices require a label that can be printed after the adhesive has been applied and/or can be written on after application to the device.

Adhesive tapes for attaching equipment drapes in sterile environment applications.

Lidding: effective protective barrier against contamination for storage or shipping.

EKG electrode bonding; 22

Surgical Drapes

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Adhesive Types:

Acrylic Polymers Widely used due to natural adhesive behavior and

wide scope of formulation/property tailoring PSAs are typically copolymer composed of ‘hard’

monomer and ‘soft’ monomer The Tg of the resultant polymer can be controlled

by the ratio of hard and soft monomers

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C4-C12 alkyl acrylates supply the initial adhesion owing to the low glass transition temperature (Tg).

Selection of the starting monomers

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Poly(methyl methacrylate) PMMA

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R-Group

The nature of alkyl group, R’, can be used to dictate the adhesives properties, by varying the chain length and hydrophilic/ hydrophobic nature of the group

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Silicones Used since mid 1960, have been utilized for

tapes, dressing, bandages Typically formulated from silicone resins and

polydimethyl siloxane gum To impart cohesive strength, the polymer and

resin are crosslinked to form a network The properties of the final adhesives can be

controlled by ratio of component and the cross-link density

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Rubber-Based PSAs Early medical adhesives were based on natural

rubber Now changed to synthetic elastomers such as

polyisoprene and polyisobutylene Polyisobutylene tend to pack tightly, results in

low air and moisture permeability The low Tg of these materials produce flexible

material, that are naturally tacky, allowing the polymer to wet out the skin surface

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Tissue glues may be arbitrary divided into two categories: biological and synthetic. Among the bilological glues fibrin-based compositions are the most widely used. Fibrin glues are used in major surgery In USA and Europa, but their use is rather restricted for several reasons. First, sutures sealed with fibrin glues can not stand large tension. Second, they contain materials of animal origin that may be the potential source of viral infection. And the last, their manufacture is very costly.

Ref.: http://eng.mediglue.ru/

Bilological Glues

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Fibrin glue (also called fibrin sealant) is a formulation used to create a fibrin clot.[1][2][3][4][5][6][7] It is made up of fibrinogen and thrombin[1] that are injected through one head into the site of a fibrin tear.[1] Thrombin is an enzyme and converts the fibrinogen into fibrin between 10 and 60 seconds and acts as a tissue adhesive.[6][8] It may also contain aprotinin, fibronectin and plasminogen.[9] This glue can be used for repairing dura tears, bronchial fistulas and for achieving hemostasis after spleen and liver trauma.[6] It is also employed in "no sutures" corneal transplantation.[10][11]

Fibrin glue applied after drying the scleral bed in an intraocular lens operation

Urethanes Urethane polymerization: diisocyanate and a diol or diamine Two part system: mix, spread and cure; Flexible joint and sealing agent.

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Other polymeric adhesives

Cure Profile of Condensation versus Addition Polymerization

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Deg

ree

of C

ure

----

->

Time

Condensation polymer

Addition polymer

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Cyanoacrylates • In 1959, a variety of cyanoacrylate adhesives were developed, some types of which are now used for surgical purposes in US, Canada, and Europe. These glues polymerize on contact with basic substances such as water or blood to form a strong bond. • The first glue developed was methyl cyanoacrylate, which was studied extensively for medical applications and was rejected due to its potential tissue toxicity such as inflammation or local foreign body reactions. Methyl alcohol has a short molecular chain which contributes to these complications.

Methyl 2- cyanoacrylate

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Methyl α-cyanoacrylate monomer polymerizes in the presence of trace amounts of almost any electron-donor compound (the initiator) by anionic vinyl polymerization, examples include water, alcohols, amines, carboxylate ions, and electron rich olefins.

R-Group

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• Cyanoacrylate adhesives were first used on wounded soldiers in Vietnam: a quick spray over the wounds stopped bleeding and bought time until conventional surgery could be performed. • Midwives found cyanoacrylate glue and medical cyanoacrylate glues useful as the tissue adhesives. Some even used Super Glue successfully in lieu of suture to close the perineum. • Surgeons have used household cyanoacrylate adhesive to apply sutureless pericardial patches that stopped bleeding in critically injured patients with torn or ruptured myocardium. Cyanoacrylates are also used in repairing corneas and retinas and as synthetic skin in treating severe burns.

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By changing the type of alcohol in the compound to one with a longer molecular chain, the tissue toxicity is much reduced. All the medical grade tissue adhesives currently available for human use contain butyl-esters.

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• Medical grade products currently available contain either butyl, isobutyl or octyl esters. They are bacteriostatic and painless to apply, break down harmlessly in tissue by hydrolysis and are essentially inert once dry. •Butyl products are rigid when dry, but provide a strong bond; octyl products are more flexible when dry, but produce a weaker bond.

•Histoacryl Blue (n-butyl cyanoacrylate) has been used extensively for a variety of surgical applications including middle ear surgery, bone and cartilage grafts, repair of cerebrospinal fluid leaks, and skin closure -- adhesives appear are basically safe. • DMSO (dimethyl sulfoxide) or acetone serve as removers.

UV-curable adhesives

One mitigating factor when it comes to the advancement of new technologies in the adhesives market is the speed with which the adhesive can be applied on the production line and how long it takes before the finished product can be placed on the market.

This is an area where UV-curable adhesives have made the strongest technological advances of any of the newer technologies currently on the market.

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Light Cure Systems Designed for high speed cure

on demand medical product assembly.

Solvent free Wide range of viscosities

designed for automated dispensing

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Light Cure Adhesives consist essentially of low or medium molecular weight

resins (called oligomers), monofunctional or multifunctional monomers, photoinitiators and/or photosensitisers;

wavelengths of 365-250nm. typically 5-15 seconds at 80-100 mW/cm2 is sufficient for

curing adhesive visible light curing materials (e.g. resins used in dental

restoration or for bonding and sealing photo-optic devices) can be cured with blue light (wavelength = 470nm).

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Typical Applications Bonding latex balloon onto PVC

lumen in catheters. Bonding high pressure latex

balloons onto urethane lumens in high pressure catheters.

Bonding balloon to multi-lumen tubes in angioplasty, thermo dilution, foley and high pressure catheters.

Bond needle to tubing in winged infusion sets.

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Flexible Adhesive Applications Bonding/sealing tracheal tubes

made of silicone rubber. Bonding/sealing extruded silicone

parts, colostomy, ileostomy, urostomy bags and appliances.

Bonding/sealing the balloon to the tracheal tube.

Bonding/sealing the cuff and tube assemblies in endotracheal, tracheotomy, gastrostomy devices, foley catheters and other fabricated silicone parts.

Sealing of inflators.

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Why Use Adhesives To join the components of medical devices Materials must meet criteria for in-vivo use

Bone repair – filling space – joining prosthesis to bone Poly(methyl methacryate) – “Lucite, Plexiglass”

Wound sealing, wound closure

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Chemistry

Benefits

Limitations

Typical Applications

Cyanoacrylate

Substrate versatility Rapid cure Adhesion to polyolefins with primers

Thermoplastic resin when cured Poor peel strength, rigid Refrigeration required

Catheter components Tube-set bonding Polyolefin bonding

Light-Curable Acrylic

Substrate versatility Good resistance properties Cure on demand

Capital expenditure for light-cure equipment

Needle assembly Anesthesia masks Heat exchangers Oxygenators Tube-set bonding

Epoxy

Substrate versatility Superior thermal and chemical resistance Low shrinkage High gap filling

Poor peel strength, rigid Exothermic reaction Two-part systems require mixing

Needle assembly Deep section potting

Polyurethane

Substrate versatility High peel Good resistance properties

Moisture sensitivity Primers required for some substrates Two-part systems require mixing

Deep section potting Bonding of tips onto various components

Biomimetic Nanostructured Medical Adhesive

Edwin P. Chan, Alborz Madhavi, Lino Ferreira, Jason Nichol, Jeffrey Karp Robert Langer (PI), Joseph Vacanti(co-PI), David Carter (co-PI), Jeffrey Borenstein (co-PI)

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Motivation There is significant medical need to develop a tough,

biodegradable adhesive that can attach strongly to tissue,

yet still accommodate the mechanical deformations

present. This material would be useful as replacement or

support for sutures and/or patches to aid in hemostasis.

The current medical adhesives are limited in applications

due to insufficient mechanical properties, difficulty in

application and/or non-tailored degradation rates with the

healing time of the tissue.

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Gecko adhesion

The footpad of many insects and lizards are decorated with fibrillar

structures called setae. Previous work has demonstrated that the

mechanisms of adhesion include the coupling of wan der Waals attraction

and pattern geometry in tuning interfacial strength.

Approach - Inspirations from Nature

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Tissue adhesion Oxidized dextran (DextOx) is used to enhance Poly(glycerol-sebacate-acrylate) (PGSA’s) surface chemical properties. As in other oxidized polysaccharides, the aldehyde groups in DextOx react with protein amine and forms imine bond. The biocompatibility and biodegradability of DextOx makes it relevant for tissue interfacing.

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DextOx

Preparation of Poly(glycerol-sebacate-acrylate) (PGSA) Elastomer

1. Fabricate silicon template by photolithography and reactive-ion etching

Nanopatterned PGSA Elastomer

• Polycondensation of PGS

• Acrylation of PGS

2. Nanomold the PGSA prepolymer with template and photocure prepolymer

3. Remove PGSA elastomer from template to generate the nanopatterned PGSA adhesive

4. Spin-coat DextOx onto PGSA elastomer to generate the final tissue adhesive

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A Gecko-inspired Bioadhesive Here, combining the design strategies of the gecko (that provides enhanced dry adhesion by surface patterns) and incorporate covalent surface chemistry to develop a new type of solid-state bioadhesive with tailored interactions with tissue.

Nanopatterns to enhance mechanical compliance with tissue

Aldehyde chemistry for tissue adhesion

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Bioadhesive Performance

Tuning Mechanical Properties: The Young’s modulus and toughness of the material can be easily tuned by the incorporation of the acrylate side groups that provides the functionality for forming a crosslinked network.

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Adhesion Testing To simulate the interaction of the bioadhesive to tissue, we measured the adhesion of the materials in aquesous conditions. Additionally, to mimic the mechanical stresses experienced by the adhesive, we used a shear-based adhesion tests to replicate the biological conditions.

Bioadhesive

Porcine intestine tissue

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Thank you for your attention