Biomaterials By: Vinita Mehrotra. Outline Definition Definition Characteristics of Biomaterials Characteristics of Biomaterials History History Biomaterials.

BiomaterialsBiomaterials

By:By:Vinita MehrotraVinita Mehrotra

OutlineOutline

DefinitionDefinition Characteristics of BiomaterialsCharacteristics of Biomaterials HistoryHistory Biomaterials ScienceBiomaterials Science Generations of BiomaterialsGenerations of Biomaterials Examples of BiomaterialsExamples of Biomaterials

Detail on Vascular GraftsDetail on Vascular Grafts Detail on Hip ReplacementsDetail on Hip Replacements

BiocompatibilityBiocompatibility Challenges Challenges Biomaterials As An Emerging IndustryBiomaterials As An Emerging Industry Companies Companies

DefinitionDefinition

A biomaterial is a nonviable material A biomaterial is a nonviable material used in a medical device, intended used in a medical device, intended to interact with biological systems. to interact with biological systems.

Defined by their application Defined by their application NOTNOT chemical make-up.chemical make-up.

Characteristics of Characteristics of BiomaterialsBiomaterials

Physical RequirementsPhysical Requirements Hard Materials.Hard Materials. Flexible Material.Flexible Material.

Chemical RequirementsChemical Requirements Must not react with any tissue in Must not react with any tissue in

the body.the body. Must be non-toxic to the body.Must be non-toxic to the body. Long-term replacement must not be Long-term replacement must not be

biodegradable.biodegradable.

HistoryHistory

More than 2000 years ago, Romans, More than 2000 years ago, Romans, Chinese, and Aztec’s used gold in Chinese, and Aztec’s used gold in dentistry.dentistry.

Turn of century, synthetic implants Turn of century, synthetic implants become available. become available.

1937 Poly(methyl methacrylate) (PMMA) 1937 Poly(methyl methacrylate) (PMMA) introduced in dentistry.introduced in dentistry.

1958, Rob suggests Dacron Fabrics can 1958, Rob suggests Dacron Fabrics can be used to fabricate an arterial be used to fabricate an arterial prosthetic.prosthetic.

History (Continued)History (Continued)

1960 Charnley uses PMMA, ultrahigh-1960 Charnley uses PMMA, ultrahigh-molecular-weight polyethylend, and molecular-weight polyethylend, and stainless steal for total hip stainless steal for total hip replacement. replacement.

Late 1960 – early 1970’s biomaterial Late 1960 – early 1970’s biomaterial field solidified.field solidified.

1975 Society for Biomaterials formed.1975 Society for Biomaterials formed.

Biomaterials ScienceBiomaterials Science

Grow cells in culture.Grow cells in culture. Apparatus for handling proteins in the Apparatus for handling proteins in the

laboratory.laboratory. Devices to regulate fertility in cattle.Devices to regulate fertility in cattle. Aquaculture of oysters.Aquaculture of oysters. Cell-silicon “Biochip”.Cell-silicon “Biochip”.

Metals

Semiconductor Materials

Ceramics

Polymers

Synthetic BIOMATERIALS

Orthopedic screws/fixation

Dental Implants Dental Implants

Heart valves

Bone replacements

BiosensorsImplantable Microelectrodes

Skin/cartilageDrug Delivery Devices

Ocular implants

Biomaterial ScienceBiomaterial Science

First Generation BiomaterialsFirst Generation Biomaterials

Specified by physicians using Specified by physicians using common and borrowed materials.common and borrowed materials.

Most successes were accidental Most successes were accidental rather than by design.rather than by design.

Second Generation of Second Generation of BiomaterialsBiomaterials

Developed through collaborations Developed through collaborations of physicians and engineers. of physicians and engineers.

Engineered implants using Engineered implants using common and borrowed materials.common and borrowed materials.

Built on first generation Built on first generation experiences.experiences.

Used advances in materials science Used advances in materials science (from other fields).(from other fields).

Third generation implantsThird generation implants

Bioengineered implants using Bioengineered implants using bioengineered materials.bioengineered materials.

Few examples on the market.Few examples on the market. Some modified and new polymeric Some modified and new polymeric

devices.devices. Many under development.Many under development.

Examples of Biomaterial Examples of Biomaterial ApplicationsApplications

Heart ValveHeart Valve Artificial TissueArtificial Tissue Dental ImplantsDental Implants Intraocular LensesIntraocular Lenses Vascular GraftsVascular Grafts Hip ReplacementsHip Replacements

Heart ValveHeart Valve

Fabricated from carbons, metals, Fabricated from carbons, metals, elastomers, fabrics, and natural elastomers, fabrics, and natural valves.valves.

Must Must NOTNOT React With Chemicals in React With Chemicals in Body.Body.

Attached By Polyester Mesh.Attached By Polyester Mesh. Tissue Growth Facilitated By Polar Tissue Growth Facilitated By Polar

Oxygen-Containing Groups. Oxygen-Containing Groups.

Heart ValveHeart Valve

Almost as soon as valve implanted Almost as soon as valve implanted cardiac function is restored to near cardiac function is restored to near normal.normal.

Bileaflet tilting disk heart valve Bileaflet tilting disk heart valve used most widely.used most widely.

More than 45,000 replacement More than 45,000 replacement valves implanted every year in the valves implanted every year in the United States. United States.

Bileaflet Heart ValvesBileaflet Heart Valves

Problems with Heart Problems with Heart Valve’sValve’s

Degeneration of Tissue.Degeneration of Tissue. Mechanical Failure.Mechanical Failure. Postoperative infection.Postoperative infection. Induction of blood clots.Induction of blood clots.

Artificial TissueArtificial Tissue

BiodegradableBiodegradable Polymer Result Polymer Result

of Condensation of Condensation of Lactic Acid of Lactic Acid and Glycolyic and Glycolyic AcidAcid

Small titanium fixture that serves as the replacement for the root portion of a missing natural tooth.

Implant is placed in the bone of the upper or lower jaw and allowed to bond with the bone.

Most dental implants are: pure titanium screw-shaped cylinders that act as roots for crowns and bridges, or as supports for dentures.

Dental ImplantsDental Implants

Dental ImplantsDental Implants

Capable of bonding to bone, a phenomenon known as "osseointegration”.

Bio-inert, there is no reaction in tissue and no rejection or allergic reactions.

Dental ImplantsDental Implants

Intraocular LensesIntraocular Lenses

Made of PMM, silicone elastomer, and Made of PMM, silicone elastomer, and other materials.other materials.

By age 75 more than 50% of By age 75 more than 50% of population suffers from cataracts.population suffers from cataracts.

1.4 million implantations in the United 1.4 million implantations in the United States yearly.States yearly.

Good vision is generally restored Good vision is generally restored almost immediately after lens is almost immediately after lens is inserted. inserted.

Intraocular LensesIntraocular Lenses

Implantation often performed on Implantation often performed on outpatient basis.outpatient basis.

Vascular GraftsVascular Grafts

Must Be Flexible.Must Be Flexible. Designed With Designed With

Open Porous Open Porous Structure.Structure.

Often Recognized Often Recognized By Body As By Body As Foreign.Foreign.

Hip-ReplacementsHip-Replacements

Most Common Medical Practice Using Most Common Medical Practice Using Biomaterials.Biomaterials.

Corrosion Resistant high-strength Corrosion Resistant high-strength Metal Alloys.Metal Alloys.

Very High Molecular Weight Polymers.Very High Molecular Weight Polymers. Thermoset Plastics.Thermoset Plastics.

Some hip replacements ambulatory Some hip replacements ambulatory function restored within days after function restored within days after surgery.surgery.

Others require an extensive healing Others require an extensive healing period for attachment between bone period for attachment between bone and the implant.and the implant.

Most cases good function restored.Most cases good function restored. After 10-15 years, implant loosens After 10-15 years, implant loosens

requiring another operation.requiring another operation.

Hip-ReplacementsHip-Replacements

Hip-ReplacementsHip-Replacements

Vascular GraftsVascular Grafts

Achieve and maintain homeostasis.Achieve and maintain homeostasis. Porous.Porous. Permeable.Permeable. Good structure retention.Good structure retention. Adequate burst strength.Adequate burst strength. High fatigue resistance.High fatigue resistance. Low thrombogenecity.Low thrombogenecity. Good handling properties.Good handling properties. Biostable.Biostable.

Vascular GraftsVascular Grafts

Braids, weaves, and knits.Braids, weaves, and knits. PorosityPorosity PermeabilityPermeability Thickness Thickness Burst strengthBurst strength Kink resistanceKink resistance Suture retentionSuture retention Wall thicknessWall thickness Tensile propertiesTensile properties Ravel resistance Ravel resistance

Vascular Grafts Vascular Grafts PermeabilityPermeability

BraidsBraids 350 to 2500 ml cm350 to 2500 ml cm22/min /min

KnitsKnits Loosely Woven KnitsLoosely Woven Knits

1200 to 2000 ml cm1200 to 2000 ml cm22/min /min Tightly Woven Knits Tightly Woven Knits

2000 to 5000 ml cm2000 to 5000 ml cm22/min /min

WeavesWeaves Below 800 ml cmBelow 800 ml cm22/min /min

Knit GraftsKnit Grafts

Filtration and FlowFiltration and Flow

µ viscosity of µ viscosity of fluidfluid

t thickness of t thickness of membranemembrane

V velocity of fluidV velocity of fluid ΔΔp pressure drop p pressure drop

across across membranemembrane

p

tvB

Void Content Kozeny-Void Content Kozeny-Carmen EquationCarmen Equation

KKo o is the Kozeny constant.is the Kozeny constant.

SSo o is the shape factor.is the shape factor. ΦΦ is the porosity. is the porosity.

2

3

2 1

1

ooSK

B

2

3

2 1

1

ooSK

B

Shape FactorShape Factor

Volume

aSurfaceAreSo

Biomaterials: An Biomaterials: An ExampleExample

Biomechanics of Artificial Biomechanics of Artificial Joints Joints

Normal versus Arthritic Normal versus Arthritic HipHip

Sir John Charnely: 1960's, fundamental principles of the artificial hip

Frank Gunston: 1969, developed one of the first artificial knee joints.

Hip replacements done in the world per year: between 500,000 and 1 million.

Number of knee replacements done in the world per year: between 250,000 and 500,000.

Of all the factors leading to total hip replacement, osteoarthritis is the most common, accounting for 65% of all total hips.

Normal versus Arthritic Normal versus Arthritic HipHip

Normal Hip: note the space between the femur and

acetabulum, due to cartilage

Arthritic Hip: No space visible in joint, as

cartilage is missing

Two design issues in Two design issues in attaching materials to boneattaching materials to bone

1)1) the geometric and material the geometric and material design of the articulating design of the articulating surfacessurfaces

2)2) design of the interface between design of the interface between the artificial joint and the the artificial joint and the surrounding bone.   surrounding bone.  

using a Polymethylmethacrylate (PMMA) cement to adhere the

metal to the bone

using a porous metal surface to create a bone

ingrowth interface

Two attachment methodsTwo attachment methods

the acetabulum and the proximal femur have been replaced. The

femoral side is completely metal. The acetabular side is composed

of the polyethylene bearing surface

Overview of femoral Overview of femoral replacementreplacement

The two materials are bonded and equal force is

applied to both

Load transfer in Composite Load transfer in Composite materialsmaterials

Comparison: Modului of Comparison: Modului of ElasticityElasticity

Modulus of elasticity of different implant materials and bone (in GPa)

Implant bondingImplant bonding

A bonded interface is characteristic of a

cemented prosthesis (left)

non-bonded interface is characteristic of a non-

cemented press fit prosthesis (right)

Degradation ProblemsDegradation Problems

Example of fractured artificial cartilage from a failed hip replacement

BiocompatibilityBiocompatibility

The ability of a material to elicit The ability of a material to elicit an appropriate biological an appropriate biological response in a specific application response in a specific application by by NOTNOT producing a toxic, producing a toxic, injurious, or immunological injurious, or immunological response in living tissue.response in living tissue. Strongly determined by primary Strongly determined by primary

chemical structure.chemical structure.

Host Reactions to Host Reactions to BiomaterialsBiomaterials

ThrombosisThrombosis HemolysisHemolysis InflammationInflammation Infection and SterilizationInfection and Sterilization CarcinogenesisCarcinogenesis HypersensitivityHypersensitivity Systemic EffectsSystemic Effects

What are some of the What are some of the Challenges?Challenges?

To more closely replicate complex tissue To more closely replicate complex tissue architecture and arrangement architecture and arrangement in vitro.in vitro.

To better understand extracellular and To better understand extracellular and intracellular modulators of cell function.intracellular modulators of cell function.

To develop novel materials and To develop novel materials and processing techniques that are processing techniques that are compatible with biological interfaces. compatible with biological interfaces.

To find better strategies for immune To find better strategies for immune acceptance.acceptance.

Biomaterials - An Biomaterials - An Emerging IndustryEmerging Industry

Next generation of medical implants Next generation of medical implants and therapeutic modalities.and therapeutic modalities.

Interface of biotechnology and Interface of biotechnology and traditional engineering.traditional engineering.

Significant industrial growth in the Significant industrial growth in the next 15 years -- potential of a multi-next 15 years -- potential of a multi-billion dollar industry.billion dollar industry.

Biomaterials Companies

•Baxter International develops technologies related to the blood and circulatory system.

• Biocompatibles Ltd. develops commercial applications for technology in the field of biocompatibility.

• Carmeda makes a biologically active surface that interacts with and supports the bodys own control mechanisms

• Collagen Aesthetics Inc. bovine and human placental sourced collagens, recombinant collagens, and PEG-polymers

• Endura-Tec Systems Corp. bio-mechanical endurance testing ofstents, grafts, and cardiovascular materials

• Howmedica develops and manufactures products in orthopaedics.

• MATECH Biomedical Technologies, development of biomaterials by chemical polymerization methods.

• Medtronic, Inc. is a medical technology company specializing in implantable and invasive therapies.

• Molecular Geodesics Inc., biomimetic materials for biomedical, industrial, and military applications

• Polymer Technology Group is involved in the synthesis, characterization, and manufacture of new polymer products.

• SurModics, offers PhotoLink(R) surface modification technology that can be used to immobilize biomolecules

• W.L. Gore Medical Products Division, PTFE microstructures configured to exclude or accept tissue ingrowth.

• Zimmer, design, manufacture and distribution of orthopaedic implants and related equipment and supplies