INDIAN INSTITUTE OF TECHNOLOGY ROORKEE

Biomaterials and Implants

By:
Dr. P. Gopinath
Professor
Department of Biotechnology
IIT Roorkee
INTRODUCTION
A biomaterial
• is a nonviable material used in a medical device, intended to interact with
biological systems.1
• is used to make devices to replace a part of a function of the body in a safe,
reliable, economic, and physiologically acceptable manner.
• is any substance (other than a drug), natural or synthetic, that treats,
augments, or replaces any tissue, organ, and body function.

The need for biomaterials stems from an inability to treat many diseases, injuries
and conditions with other therapies or procedures :
• replacement of body part that has lost function (total hip, heart)
• correct abnormalities (spinal rod)
• improve function (pacemaker, stent)
• assist in healing (structural, pharmaceutical effects: sutures, drug release)
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EXAMPLES OF USES OF BIOMATERIALS
Organ/Tissue Examples

heart pacemaker, artificial valve, artificial heart

eye contact lens, intraocular lens

ear artificial stapes, cochlea implant

bone bone plate, intramedullary rod, joint

prosthesis, bone cement, bone defect
repair

kidney dialysis machine

bladder catheter and stent

muscle sutures, muscle stimulator

circulation artificial blood vessels

skin burn dressings, artificial skin

endocrine encapsulated pancreatic islet cells

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Material Attributes for Medical Applications

Biocompatibilty
• Non-carinogenic, non-pyrogenic, non-toxic, non-allergenic, blood compatible,
non-inflammatory
Sterilizability
• Not destroyed or severely altered by sterilizing techniques such as
autoclaving, dry heat, radiation, ethylene oxide
Physical Characteristics
• Strength, toughness, elasticity, corrosion-resistance, wear-resistance, long-
term stability
Manufacturability
• Machinable, moldable, extrudable

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 Biocompatibility

Biocompatibility
• The ability of a material to perform with an appropriate host response in
a specific application.
Host response
• The reaction of a living system to the presence of a material.

https://www.sciencedirect.com/science/article/pii/S0168365916300682#f0005
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Sterilization Methods
Autoclave (Steam)
• High temperature process (121 – 134°C)
• Commonly for repeat sterilization (e.g. instruments)
• Cheap
Ethylene Oxide (EO)
• Low temperature process (for heat sensitive materials, e.g.
UHMWPE)
• Residual gas can linger
• Environmental impact and occupational hazard
Gamma Radiation
• Very effective
• Can cause polymer oxidation and crosslinking

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Classes of Biomaterials
Metals
• stainless steel, cobalt alloys, titanium alloys.

Ceramics
• aluminum oxide, zirconia, calcium phosphates.

Polymers
• silicones, poly(ethylene), poly(vinyl chloride),

polyurethanes, polylactides.

Natural polymers
• collagen, gelatin, elastin, silk, polysaccharides.

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FDA Guidelines for Biocompatibility Testing of
Permanent Implant Devices
Tissue/bone Blood
Cytotoxicity (toxicity to X X
cells)
Sensitization (induced X X
allergic response)
Irritation or Intracutaneous O X
Reactivity
Acute Systemic Toxicity O X
Sub-Chronic Toxicity (24 O X
hours to 10% of lifespan)
Genotoxicity (exposure X X
changes cells’ DNA)
Implantation X X
Hemocompatibility - X
X = ISO evaluation test
O = additional tests may be applicable
http://www.fda.gov/cdrh/bbtable1.html

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 IMPLANT
 IMPLANT
• It is defined as insertion of any object or a material , which is
alloplastic in nature either partially or completely into the body
for therapeutic , experimental , diagnostic or prosthetic
purpose. .

 First Generation Implants

 Second generation implants
 Third generation implants

https://www.fda.gov/medicaldevices/productsandmedicalprocedures/implantsandprosthetics/metalonmetalhipimplants/default.htm

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 First Generation Implants

 “ad hoc”(unplanned) implants.

 specified by physicians using common and borrowed materials.
 most successes were accidental rather than by design.

Examples — First Generation Implants

• Gold fillings, wooden teeth, PMMA dental prosthesis

• Steel, gold, ivory, etc., bone plates Intraocular implants

• Glass eyes and other body parts

• Dacron and parachute cloth vascular implants

http://about-eyes.com/why-you-need-to-know-what-lens-your-eye-surgeon-will-implant-
during-cataract-surgery/ Vascular graft
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Second generation implants

 Engineered implants using common and borrowed materials

 Developed through collaborations of physicians and engineers
 Built on first generation experiences
 Used advances in materials science (from other fields)

Examples — Second generation implants

• Titanium alloy dental and orthopaedic implants

• Cobalt-chromium-molybdinum orthopaedic implants

• UHMW polyethylene bearing surfaces for total joint replacements

• Heart valves and pacemakers

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 Artificial Hip Joints

Artificial Hip replacements

http://www.totaljoints.info/Hip.jpg https://www.columbusanteriorhipreplacement.com/treatment/

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Substitute Heart Valves

https://newsroom.clevelandclinic.org/2018/04/04/cleveland-clinic-surgeons-pioneer-new-minimally-invasive-
heart-valve-surgery/

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Third generation implants

 Bioengineered implants using bioengineered materials

 Few examples on the market
 Some modified and new polymeric devices
 Many under development

Example - Third generation implants

Artificial Skin

• Tissue engineered implants designed to regrow rather than replace tissues

• Integra life sciences artificial skin
• Genzyme cartilage cell procedure
• Some resorbable bone repair cements
• Genetically engineered “biological” components
http://www.thehansindia.com/posts/index/Education-&-Careers/2016-05-
10/New-artificial-skin-to-smooth-out-wrinkles/227273

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SEM displaying the cross section of a composite disk, which had
been seeded with cultured bone marrow stromal cells.

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Classification of biomaterials
 First generation: INERT
• Do not trigger any reaction in the host: neither rejected nor
recognition “do not bring any good result”

 Second generation: BIOACTIVE

• Ensure a more stable performance in a long time or for the period you
want

 Third generation: BIODEGRADABLE

• It can be chemically degraded or decomposed by natural effectors
(weather, soil bacteria, plants, animals)

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Mechanical Properties of Metals

How do metals respond to external loads?

 Stress and Strain
• Tension
• Compression
• Shear
• Torsion
 Elastic deformation
 Plastic Deformation
 Yield Strength
 Tensile Strength
 Ductility
 Toughness
 Hardness

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Stress-Strain Behavior

Elastic deformation
Reversible: when the stress is removed, the
material returns to the dimension it had before the
loading. Usually strains are small (except for the
case of plastics).

Plastic deformation
Irreversible: when the stress is removed, the
material does not return to its previous dimension.

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Stress-Strain Behavior: Plastic
deformation

Plastic deformation:
Stress and strain are not proportional
the deformation is not reversible
deformation occurs by breaking and
rearrangement of atomic bonds (in
crystalline materials primarily by
motion of dislocations).

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Typical mechanical properties of metals

 The yield strength and tensile strength vary with prior thermal and mechanical
treatment, impurity levels, etc.

 This variability is related to the behavior of dislocations in the material. But

elastic moduli are relatively insensitive to these effects.

 The yield and tensile strengths and modulus of elasticity decrease with
increasing temperature, ductility increases with temperature.

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Mechanics of Materials

 The point up to which the stress and strain are linearly related is called the
proportional limit.
 The largest stress in the stress strain curve is called the ultimate stress.
 The stress at the point of rupture is called the fracture or rupture stress.
 The region of the stress-strain curve in which the material returns to the
undeformed state when applied forces are removed is called the elastic region.
 The region in which the material deforms permanently is called the plastic
region.
 The point demarcating the elastic from the plastic region is called the yield
point. The stress at yield point is called the yield stress.

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Mechanics of Materials

 The permanent strain when stresses are zero is called the plastic strain.
 The off-set yield stress is a stress that would produce a plastic strain
corresponding to the specified off-set strain.
 A material that can undergo large plastic deformation before fracture is called
a ductile material.
 A material that exhibits little or no plastic deformation at failure is called a
brittle material.
 Hardness is the resistance to indentation.
 The raising of the yield point with increasing strain is called strain hardening.
 The sudden decrease in the area of cross-section after ultimate stress is
called necking.

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Viscoelasticity

Definition:
Time-dependent material behavior where the stress response of that material depends
on both the strain applied and the strain rate at which it was applied!
Examples
• biological materials
• polymer plastics
• metals at high temperatures

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Effect of the Host on the Implant

 Physical – mechanical effects

• Abrasive wear
• Fatigue
• Stress corrosion, cracking
• Corrosion
• Degeneration and dissolution
 Biological effects
• Absorption of substances from tissues
• Enzymatic degradation
• Calcification

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Types of Metallic Implants

 Stainless steel
 Cobalt Based Alloys
 Titanium Alloys
Stainless steel

Cobalt Based Alloys Titanium Alloys

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 Stainless Steels
 Fe 60-65 wt%, Cr 17-19 wt %, Ni 12-14 wt%
 Carbon content reduced to 0.03 wt% for better resistance to in vivo
corrosion.
• Why reduce carbon: Reduce carbide (Cr23C6) formation at grain
boundary. Carbide impairs formation of surface oxide
• Why add chromium: corrosion resistance by formation of surface
oxide.
• Why add nickel: improve strength by increasing face centered cubic
phase (austenite)

https://www.pressuretechnology.com/hip-applications-biomedical.php

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Cobalt Alloys: ASTM F75

 Co-Cr-Mo
 Surface oxide; thus corrosion resistant
 Wax models from molds of implants
 Wax model coated with ceramic and wax melted
away
 Alloy melted at 1400°C and cast into ceramic molds.

http://pdf.directindustry.com/pdf/arcam/cobalt-chrome-astm-f75/19734-
604624.html

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 Titanium Based Alloys

 Lighter
 Good mechanical properties
 Good corrosion resistance due to TiO2solid oxide layer
 Ti-6% wt Al-4% wt V (ASTM F136) is widely used
 Contains impurities such as N, O, Fe, H, C

http://www.assureasmile.com/miami-dentist-blog/titanium-dental-
https://www.azom.com/article.aspx?ArticleID=14935
implants-dangerous/

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Metallic Biomaterials
Advantages Disadvantages

• High strength • High moduls

• Fatigue resistance • Corrosion

• Wear resistance • Metal ion sensitivity and toxicity

• Easy fabrication • Metallic looking

• Easy to sterilize

• Shape memory

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Ceramic
 Any of various hard, brittle, heat-resistant and corrosion-resistant materials
made by shaping and then firing a nonmetallic mineral, such as clay, at a
high temperature

Clinical success requires:

• Achievement of a stable interface with connective tissue

• Functional match of the mechanical behavior of the implant with the

tissue to be replaced

Critical Issues:

• Integrity of bioceramic

• Interaction with the tissue

http://epaper.dental-tribune.com/dti/5b14f409eb21e/#0

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Bioceramics
• Alumina

• Zirconia (partially stabilized)

• Silicate glass

• Calcium phosphate (apatite)

• Calcium carbonate

http://researchofmarket.com/bioceramics-market/

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Hydroxyapatites (HA)

 Chemically similar to mineral component of bones.

 It will support bone in growth and Osseo integration.

 when used in orthopedic, dental and maxillofacial applications.

 Chemical formula: Ca5(PO4)3OH

 The chemical nature of hydroxyapatite lends itself to substitution; common

substitutions involve carbonate, fluoride and chloride substitutions for
hydroxyl groups.

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Uses for HA

 Facial augmentation with hydroxyapatite has been used for the following

corrections: Cheek, Chin, Jaw, Nose, Brow bone.

 Skeletal repair biomaterials.

 Ocular prosthesis.

 Hydroxyapatite from coral.

 The eye muscles can be attached directly to this implant, allowing it to move
within the orbit-just like the natural eye.

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Calcium Phosphate Bioceramics

 There are several calcium phosphate ceramics that are considered

biocompatible; most are resorbable and will dissolve when exposed to
physiological environments.

 Hydroxyapatite is thermodynamically stable at physiological pH values;

actively takes part in bone bonding, forming strong chemical bonds with
surrounding bone.

 Mechanical properties unsuitable for load-bearing applications such as

orthopaedics.

 Used as a coating on materials such as titanium and titanium alloys, where

it can contribute its 'bioactive' properties, while the metallic component
bears the load.

 Coatings applied by plasma spraying.

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Bioceramic
Advantages Disadvantages

• High compression strength • High modulus (mismatched with

• Wear & corrosion resistance bone)

• Can be highly polished • Low strength in tension

• Bioactive/inert • Low fracture toughness

• Difficult to fabricate

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 Polymeric Biomaterials

 What is a polymer?
Long chain molecules that consist of a number of repeating units (mers).

Fabricated from monomers which change somehow in polymerization.

Loss of H20, HCl or other molecule.

Polymer properties are more complex than for simpler materials.

 Types of polymers
Biological polymers
• DNA, cellulose, starch, proteins, rubber, etc.
• Often reconstituted to form usable polymer.
• Mainly collected from animals.
Synthetic polymers
• Fabricated from petroleum products (generally).
• May be also a modified biological polymer.
• Most plastics and similar materials.
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Polymeric Biomaterials

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Classification

Polymers

Thermoplastics Thermosets Elastomers or

Rubbers

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Classes of Polymers (I)

 Thermoplastic polymers
• Long chains with very limited or no cross-linking.
• They behave in a plastic, ductile manner.
• Melt when heated and are thus easily remolded and recycled.

 Thermoset polymers
• Highly cross-linked, 3D network structures.
• Generally brittle (at most temperatures).
• Decompose when heated and can’t easily be reshaped or recycled.

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 Classes of Polymers (II)

 Elastomers and rubbers elastomer

• Large amounts of elastic deformation

• Some (light) cross-linking

 Typically, about 1 in 100 molecules are cross-linked on

average

 Average number of cross-links around 1 in 30 yields a thermoset

more rigid and brittle material (closer to a thermoset)

• Crosslinks allows material to return to original shape without

plastic deformation

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PE (Polyethylene) and PP (Polypropylene)

PE (Polyethylene) PP (Polypropylene)

• Used in high density form as tubing

• High rigidity
for drains and catheters
• Good chemical resistance
• Ultra high molecular weight form used
• Good tensile strength
as acetabul component in artificial
hips and other prosthetic joints • Excellent stress cracking resistance

• Has good toughness and wear • Used for sutures and hernia repair

resistance

• Resistant to lipid absorption

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PTFE (Polytetrafluoroethylene) and
PVC(Polyvinylchloride)
PTFE (Polytetrafluoroethylene) PVC(Polyvinylchloride)

• Made flexible and soft by the

• Very hydrophobic
addition of plasticizers
• Good lubricity
• Not suitable for long term use
• Low wear resistance
because plasticizers can be
• Used for catheters and vascular
extracted by the body
grafts
• Used as tubing for blood
transfusions, feeding and dialysis,
and blood storage bags

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Elastomer vs. Thermoplastic Elastomers

 Some amorphous polymer exhibit elastomeric behavior, yet have no

chemical crosslinks
• Usually block copolymers possessing both rubbery regions and stiff regions
in the chain

• Physical interactions between stiff chain regions act a physical “crosslinks”

• Rubbery regions allow large deformations

• Thermoplastic in nature; can be melted since there are no chemical

crosslinks

Styrene butadiene styrene (SBS)

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Thermosets
 Disadvantage

Thermosets are difficult to re-form.

 Advantages in engineering design applications

• High thermal stability and insulating properties.

• High rigidity and dimensional stability.

• Resistance to creep and deformation under load.

• Light-weight.

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Thermosets

 Crosslinking of thermosets
• 10-50% of the ‘mers’ in a chain are crosslinked.
• Heat treatment, vulcanization processes link existing chains.
• Two part chemistries (resin and curing agent) are mixed and react
at room temp or elevated temperatures – multi-functional end
groups

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Polymers as Biomaterials
 Hydrogels
• Swellable materials, usually acrylic
copolymers, e.g. poly(2-hydroxyethyl
methacrylate): PHEMA
 Piezoelectric materials
• Materials that generate transient
electrical charges on their surfaces upon
mechanical deformation, e.g.
polyvinylidene fluoride, collagen
 Resorbable materials
• Resorbed with time, e.g. polyglycolic
and polylactic acid

https://www.sciencedirect.com/science/article/pii/S007967001200086X

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Fluorinated Polymers

 PTFE

• Plain or expanded

• Vascular grafts, sutures, middle ear prostheses

 Fluorocarbons

• High affinity for oxygen

• Blood substitutes
PTFE unsuccessful in
 Poly-Vinylidene Fluoride (PVDF) joint replacements

• Piezoelectric

• Actuators, nerve guidance

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Polymethyl methacrylate(PMMA)
• PMMA

• A hydrophobic linear chain polymer that is transparent, amorphous and

glassy at room temperature (also known as plexiglass or lucite).

• Good light transmittance, toughness, and stability.

• A good material for intraocular lenses and hard contact lenses.

• Also used as a bone cement.

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Polyethylene
• PE

• High density form (HDPE)

– Used for tubing in catheters and drains

• High molecular weight form (UHMWPE)

– Contact surface in artificial hips, knees

• Good toughness, resistance to fat and oils, and low cost

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Polyethylene Glycol
• PEG

• Short chain neutral hydrophilic polymer

• Shown to repel cells due to surface energy

• Used for coatings – non-thrombogenic

• Wound healing: polymerization on the wound

• Microencapsulation and drug delivery

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Biological Polymers

 Many cellular and extracellular materials are polymers

1. Polysaccharides (made from monosaccharide's)

• Cellulose

• Alginate

2. Proteins (made from amino acids)

• Collagen

• Actin

• Fibrin

3. Nucleic Acids (made from nucleotides)

• DNA

• RNA

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Silicones
• Silicone polymers

• e.g. Polydimethylsinoxane (PDMS)

• No carbon backbone – silicone and oxygen instead

• Elastomers (with crosslinks)

• Silicones as biomaterials

• Very low Tg

• Excellent flexibility and stability

• Used in catheters, pacemaker leads, vascular grafts, and breast and facial
implants

• High oxygen permeability - membrane

• oxygenators

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Common clinical applications and types of polymers
used in medicine

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Polymers In Specific Applications
Application Properties and design requirements Polymers used

Dental •stability and corrosion resistance, plasticity PMMA-based resins for

•strength and fatigue resistance, coating activity fillings/prosthesis
•good adhesion/integration with tissue polyamides
•low allergenicity poly(Zn acrylates)
Ophthalmic •gel or film forming ability, hydrophilicity polyacrylamide gels
•oxygen permeability PHEMA and copolymers
Orthopedic •strength and resistance to mechanical restraints PE, PMMA
and fatigue PL, PG, PLG
•good integration with bones and muscles

Cardiovascular •fatigue resistance, lubricity, sterilizability silicones, Teflon,

•lack of thrombus, emboli formation poly(urethanes), PEO
•lack of chronic inflammatory response

Drug delivery •appropriate drug release profile PLG, EVA, silicones,

•compatibility with drug, biodegradability HEMA, PCPP-SA
Sutures •good tensile strength, strength retention silk, catgut, PLG, PTMC-
•flexibility, knot retention, low tissue drag G
PP, nylon,PB-TE

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Polymeric Biomaterials

Advantages Disadvantages
• Easy to make complicated items • Leachable compounds

• Tailorable physical & mechanical • Absorb water & proteins etc.

properties • Surface contamination
• Surface modification • Wear & breakdown
• Immobilize cell etc. • Biodegradation
• Biodegradable • Difficult to sterilize

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Soft Tissue Implants

 Attempts have been made to replace or augment most of the soft

tissues in the body

• Connective tissues: skin, ligament, tendon, cartilage

• Vascular tissue: blood vessels, heart valves

• Organs: heart, pancreas, kidney

• Other: eye, ear, breast

 Most soft tissue implants are constructed from synthetic polymers

• Possible to choose and control the physical and mechanical properties

• Flexibility in manufacturing

 "Soft tissue implants" can also be designed for soft tissue repair

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Sutures
 Used to repair incisions and lacerations

Important characteristics for sutures:

• Tensile strength

• Flexibility

• Non-irritating

https://www.saintlukeskc.org/health-library/suture-care

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 Tissue Adhesives

 Used for repair of fragile, non-suturable tissues

– Examples: Liver, kidney, lung

 The bond strength for adhesive closed tissues is not as strong after 14 days
as for suture closed tissues

https://www.amazon.com/Abbott-Laboratories-GLUture-Topical- https://www.jucm.com/using-tissue-adhesives-in-urgent-care/
Adhesive/dp/B00IJVQVO6
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 Percutaneous Implants

 Refers to implants that cross the skin barrier

– In contact with both the outside environment and

the biological environment

 Used for connection of the vascular system to

external "organs"

• Dialysis

• Artifical heart

• Cardiac bypass

 Also used for long term delivery of medication or

nutrition (IV)

http://www.nmcheartcare.ae/pacemaker-implants-and-percutaneous-closure-device-implants/

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Percutaneous Implants

 Main Problems:
• Attachment of skin (dermis) to implant difficult to maintain through in
growth due to rapid turnover of cells
• Implant can be extruded or invaginated due to growth of skin around the
implant
• Openings can also allow for the entrance of bacteria, which may lead to
infection

https://www.ijaaonline.com/article/S0924-8579(17)30109-7/pdf

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 Artifical Skin
• Is actually a percutaneous implant -- contacts
both external and biological environments

• No current materials available for permanent

skin replacement

• Design ideas:

• Graft should be flexible enough to conform

to wound bed and move with body

• Should not be so fluid-permeable as to

allow the underlying tissue to become
dehydrated but should not retain so much
moisture that edema (fluid accumulation)
develops under the graft https://www.kidsdiscover.com/quick-reads/took-two-people-invent
artificial-skin/

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Artificial Skin - Possibilities
 Polymeric or collagen-based membrane

• Some are too brittle and toxic for use in burn victims

• Flexibility, moisture flux rate, and porosity can be controlled

 Fabrics and sponges designed to promote tissue in growth

• Have not been successful

 Immersion of patients in fluid bath or silicone fluid to prevent early

fluid loss, minimize breakdown of remaining skin, and reduce pain

 Culturing cells in vitro and using these to create a living skin graft

• Does not require removal of significant portions of skin

62
 Soft Tissue Augmentation

 Generally used for reconstructive or cosmetic enhancement

 Functions include one or more of the following
• Space filler
• Mechanical support
• Fluid carrier or storer
 Common applications for soft tissue augmentation are:
• Maxillofacial implants
• Eye and ear implants
• Fluid transfer implants
• Breast implants

63
Maxillofacial implants
 Designed to replace or enhance hard or soft

tissue in the jaw and face

 Intra oral prosthetics (implanted) are used to

reconstruct areas that are missing or defective

due to surgical intervention, trauma, or

congenital condition

 Must meet all biocompatibility requirements

 Metals such as tantalum, titanium, and Co-Cr

alloys can be used to replace bony defects

 Polymers are generally used for soft tissue

augmentation
https://www.omniagmd.com/product/maxillofacial-implants
• Gums, chin, cheeks, lips, etc.

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Maxillofacial implants

 Injectable silicone had been examined for use in correcting facial

deformities; however, it has been found to cause severe tissue reactions in

some patients and can migrate

 Extra oral prosthetics (external attachment) should:

• Match the patients skin in color and texture

• Be chemically and mechanically stable

• Not creep, change colors, or irritate skin

• Be easily fabricated

• Have been fabricated out of numerous polymers

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Fluid Transfer Implants

• May be designed as permanent implants to treat chronic problems

• Hydrocephalus

• Build up of cerebrospinal fluid in the brain

• Can result in brain damage if pressure becomes too high

• Treated by draining the fluid to the vascular system or abdominal cavity

• Uses a permanent shunt from the ventricles of the brain, under the skin, to
the receiving tissue

• Tubing is made of silicone rubber made radiopaque to allow for

observation with x-rays

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Fluid Transfer Implants

 Ear Infections
• "Tubes" in the ears are drainage tubes designed to remove fluid from
the middle ear
• Constructed from teflon or other inert materials
 Not permanent implants (removed after several years)

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Orthopaedic Soft Tissue
 Replacement of cartilage, ligaments, and tendons

 Difficult to obtain fixation with bone

• Screws or pins involve stress concentrations and the possibility of

corrosion

• Strength of anchorage depends on thickness of cortical bone at

attachment site

 In many cases autographs are used

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Orthopaedic Soft Tissue
 Allographs - cryo-preserved, fresh-frozen, or freeze dried specimens taken
from cadavers
• Often attached to treated bony insertion sites which can be used as
bone grafts
• Preservation and cold sterilization procedures may adversely affect
properties of implants
 Available from tissue banks.

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Thank you

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