Biomaterials: Materials Used To Safely Replace or Interact With Biological Systems

Institute for Genomics and Bioinformatics
Biomaterials
Materials used to safely replace or interact with biological systems
Assoc. Prof. Dr. Juliane Bogner-Strauss
Vorlesungsunterlagen: IGB Homepage,

Education, Biomaterials
Recommended literature:
“Biomaterials, an introduction” J. Park and R.S. Lakes 2007
Springer Science
and
“Biomaterials Science” BD. Rafner 2004 Elsevier Academic Press
(available from the TUG-Bib in e-version) Allograft material. (A) clinical aspect of a
mandibular bone defect; (B) freeze-dried
demineralized bone allograft; (C) biomaterial
filling the bone defect associated with a non-
absorbable barrier.
Biomaterials WS2008 Courtesy R. Zenz 1

A very short history of biomaterials
 The Romans, Chinese, and

Aztec used gold in dentistry
more than 2000 years ago.
 Glass eyes and wooden teeth

have been used trough much
of the recorded history.

A very short history of biomaterials
 Synthetic plastics became available at the turn of last

century.
 PMMA (Polymethyl methacrylate) was intoduced in
dentistry in 1937.
 Experiments with parachute cloth (Vinyon N) as vascular
prosthesis after world war II.
 In the early 1960s total hip replacement made of PMMA,
ultrahigh-molecular-weight polyurethan, and stainless
steel.

Notable Developments Relating to Implants

Year Investigator Development_________________________
Late 18th–19th century Various metal devices to fix fractures; wires
and pins from Fe, Au, Ag, and Pt
1860–1870 J. Lister Aseptic surgical techniques
1893–1912 W.A. Lane Steel screws and plates for fracture fixation
1909 A. Lambotte Brass, Al, Ag, and Cu plate
1912 Sherman Vanadium steel plate, first alloy developed
exclusively for medical use
1926 E.W. Hey-Groves Used carpenter's screw for femoral neck
fracture
1931 M.N. Smith-Petersen Designed first femoral neck fracture fixation
nail made originally from stainless steel,
l ater changed to Vitallium®
1938 P. Wiles First total hip replacement
1946 J. and R. Judet First biomechanically designed hip prosthesis;
first plastics used in joint replacement
1940s M.J. Dorzee, A. Franceschetti Acrylics for corneal replacement
1952 A.B, Voorhees, A. Jaretzta, First blood vessel replacement made of parachute cloth
A.H. Blackmore
1958 S. Furman, G. Robinson First successful direct stimulation of heart
1960 A. Starr, M.L. Edwards Heart valve
1970s W.J. Kolff Experimental total heart replacement
1990s Refined implants allowing bony ingrowth
1990s Controversy over silicone mammary implants
2000s Tissue engineering
2000s Nanoscale materials

Various implants and devices for replacement or enhancement

Biomaterial science - definitions

 Biomaterial — A biomaterial is a nonviable material used in a
(medical) device intended to interact with biological systems
(Williams 1987).
 Biocompatibility — The ability of a material to perform with an

appropriate host response in a specific application (Williams 1987).
 Host Response — The response of the host organism (local and

systemic) to the implanted material or device.
E.g.: A hemodialysis system serving as an artificial kidney requires

materials that must function in contact with the patients`s blood and
exhibit appropriate membrane permeability and mass transport
characteristics.

Biocompatibility

Examples of biomaterial applications (USA)
 Substitute heart valves (45,000/year)

 Artifical hips (90,000/year)
 Dental implants (275,000/year)
 Intraocular lenses (1.4 millions/year)

Examples of biomaterial applications (USA)

Many materials are used

Interdisciplinary interactions are needed
Different disciplines have to work

together, starting from the identification
of a need for a biomaterial through
development, manufacture, implantation,
and removal from the patient.
engineering
medical
biological engineering
engineering
biology medicine

Subjects integral to biomaterials science

 Toxicology
– Biomaterials should not be toxic.
– „smart bombs“ (drug release systems that seeks out cancer cells
and destroy them)
– A biomaterial should not give off anything from its mass (problem
with many low-molecular-weight polymers).
 Biocompatibility
– Non tumorigenic
– Normal wound healing, no infections
– No hypersensitivity
 Mechanical and performance requirements
– Hip prothesis: strong and rigid,
– Articular cartilage substitute: soft and elastomeric
– Dialysis membrane: strong and flexible
– ........

Properties of materials
 Bulk properties
 Suface properties Bulk
Material
– Synthetic materials have specific
bulk and surface characteristics.
– They must be known prior to any
medical application.
Adsorbed layer of Cells in
– Do they change over time in vivo? Surface Layer water, ions & biological
of Material proteins fluid
This information must be evaluated within the context of the

intended biomedical use, since applications and host tissue
responses are quite specific within areas (e.g. Cardiovascular:
flowing blood contact; orthopedic: functional load bearing).

Properties and structure
 Structure can be viewed at many levels:

– Atomic or molecular
– Ultrastructural
– Microstructural
 Each level of structure in a material affects the overall properties of

that material in different, and sometimes conflicting, ways.

Atomic or molecular level
 Types of bonding
– Almost all the physical properties depend on the nature and

strenght of the interatomic bonds:
• Shape, density, ect.
• Heat conduction
• Electrical conduction
• Biochemical reactivity
• Surface properties
• Load-deformation behavior

Bulk properties of materials
Solids are held together by strong interatomic forces.
 Metallic bonding
 Covalent bonding
 Ionic bonding
 Weak bonding

Metallic bonding
 Positively charged ion cores with negative electrons circulate around

the core.
– Free valence electrons which can "travel" about the material.
– Electrical charge is neutralized on average.
– Bonds are non-directional (isotropic).
 Allow plastic deformation electrons

– Atom position is non discriminative
 Good electrical and heat conductance

Covalent bonding
 Formed between non-metallic atoms when the valence electrons are

shared to fill each outer valence orbital.
– Carbon atoms sharing pairs of electrons.
– Highly directional, allowing chains of monomers to be formed.
 Poor electrical and heat conductance.
electrons

Ionic bonding
 Metallic atom shares one or more electrons with the non-metallic

atom.
– Cation is surrounded by as many anions as possible.
– Reduces mutual repulsion of cations.
– Packing is a function of relative atomic sizes.
 Forms a crystalline structure.
 Results in low electrical and
head conductivity and low
chemical reactivity.

Weak or secondary bonding
 Van Waals bonds:

– Form among hydrogen, oxygen
and other atoms.
– Not highly directional.
– High number of possible bonds results in strength.
 Hydrogen bonds Hydrogen bonds:

– Formed when hydrogen is covalently bonded to an
electronegative atoms.

Relative bond strenght

 Heat of vaporization (KJ/mol)
– Van der Waals He 0.14

N2 13
– Hydrogen Phenol 31
HF 47
– Metallic Na 180
Fe 652
– Ionic NaCl 1062

MgO 1880
– Covalent Diamond 1180

SiO2 2810

Ultra-structual level
 Atomic structures defined by bonding:

– Crystalline
• Form organized three dimensional lattices with only minor defects.
– Non- crystalline (amorphous)

• Form random patterns of connections.
– Mixed

Metals-Crystalline
 Materials containing only metallic atoms:

– Single elements
– In combination (alloys)
 Single elements can closely pack.
 Alloys will pack due to relative sizes of the atoms:
– Could be stable or unstable packing of interstitial atoms.
stable stable unstable

 Packing efficiency:
– Defined by the coordination number.

Metals
 Exhibit metallic bonding in the solid state.
 Mixtures or solutions of different metals are alloys.
 85% have one of these crystal structures:
FCC (face centered cubic) HCP (hexagonal close packed) BCC (body centered cubic)
Every atom (ion) is surounded by 12 (FCC, HCP) or 8 (BCC)

neighbors.

Polymers-Amorphous
 Material behavior is more a factor of molecular features than inter-

atomic bonds.
 Very long chain molecules:
– The mer (monomer) is the basic unit.

– Molecule containing one or more atoms that can each participate
in two or more covalent bonds.

Polymers
 Covalent bonding forms the chain structure:

– Fixed bond length.
– Permits rotation of adjacent atoms about its axis.
– When atoms (carbon) forms multiple covalent bonds, the sizes of
the angles between the bonds involving a particular atom is
fixed.
 Other covalent, hydrogen or van der Waals bonds link between

chains:
– Wide variety of conformations possible.

Polymers
 Two (3) classes of polymers:

– Thermoplastic
• “Straight” - have little or no branching
• Can be melted and remelted
• Will reform into similar structure
– Thermosetting
• Side chains are present
• Side chains form links between chains
• Will not reform equally upon remelting
– Elastomers

Ceramics-Crystalline
 Inorganic, non-metallic materials:

• Those materials that aren’t metals or polymers
– Most contain one or more metallic oxides along with other compounds.
– May have varied phases:

• Crystalline, single or poly crystalline, or amorphous

Ceramics
 Combinations of ionic and covalent bonding.
– Must be electrically neutral:

• Requires specific organization of covalently bonded atoms.
• Leads to complex crystal or mixed structures.
– Combined cation anion structure results in mechanical and

thermal/electrical properties:
• Good thermal and electrical insulator.
• Resistant to high temperatures and severe environment.

Ceramics
 Nearly inert ceramics:

– Alumina (Al2O3)
– Carbon (diamond)
 Surface reactive ceramics:

– Sites for oxidation or protein bonding on surfaces.
 Highly reactive:
– Can be resorbed by exposure to biological environment:
• Calcium phosphate

Inorganic glasses-amorphous
 To make:
– Take ceramic material and melt.
– With cooling the material does not return to a crystal structure.
 Form structures that do not repeat throughout the aggregates:

– Silicates and phosphates
• Brittle
• Low heat and electrical conduction

Ultra-structural level in crystalline materials
 Imperfections in crystalline structures:

• Defects play a major role in determining the physical
properties of a material.
– Point defects
– Line defects
– Grain boundaries

Point defects
 Vacancies:
– Empty sites in the crystal formation.
– Allow for increased atomic diffusion.
– Maintains charge balance.
– Relative size of atoms controls.

Point defects
 Substitutional atoms:
– Sites filled by differing atoms.
– Result in atomic distortion if atomic radii differ.
 Interstitial atoms:
– Atoms fitted into the crystal formation.
– Less frequent in closely packed structures.

Line defects
 Plane of atoms is
displaced or
dislocated from its
regular lattice space.

Line defects
 Act to reduce the strength and stiffness of the solid:
– An increase in energy along the dislocation.

• Less energy must be added to move the planes or
break the bonds at this location.
– Effect is concentration dependent.
• Many line defects will act to strengthen a material
as they interfere with the progression of
dislocations.

Grain boundaries
 Planar defect between crystals

in a polycrystalline material.
– Typically 1 to 2 atomic
distances wide.
– Within a grain, all crystalline

unit cells are aligned.
– At grain boundaries, there is a transition zone where

atoms are not aligned with either grain.

Grain boundaries
 Less efficient atomic packing at grain boundaries:

– Allows for diffusion of gases or liquids.
 Increases chemical reactivity.
 Can prevent progression of line defects:

– Alignment of grains.
– Strengthening material.

Microstructural level in crystalline

materials
 Grain structure can vary in:
– Grain size
– Preferred orientation
– Grain shape

Grain size
 A larger grain size number (GS#) indicates a higher
number of grains and grain boundaries per unit volume.
– Fine grained structure is stronger than a coarse one

at normal temperatures.
• Grain boundaries interfere with the movement of
atoms during deformation.
 A fine-grained structure is weaker and softer than a

coarse one at elevated temperatures.
– Grain boundaries are a source of weakness above

temperatures where atoms start to move significantly.
Grain shape
 Equiaxed
– Approximately equal dimensions in 3 directions
 Plate-like
– One dimension smaller than other two
 Columnar
– One dimension larger than other two
 Dendritic (tree-like)

Grain orientation
 Description of the crystal orientation within grains:
– Typically random orientation within metals.
• Ferric metals align to Earth’s magnetic field.
 Preferred orientation can be manipulated to obtain

improved material properties.

Ultra-structural level in amorphous

materials
 In network materials:
– Vacancies
– Substitutional atoms
– Interstitial atoms
• SiO2 with Na+

• With more O, network is broken, becomes
crystalline.

Ultra-structural level in polymers
 Polymer material behavior is a function of:
– Linearity, branching and cross-linking of polymer

chain(s).
– Symmetry of chain.
– Degree of crystallinity.

Polymers
 Organization of chain
molecules within the
polymer.
– Linear
– Branched
– Cross-linked

Ultra-structural level in polymers
 Co-polymer can form (similarly as

substitutional atoms) in the
polymer chain:
– Random
– Alternating
– Block
– Graft

Side elements of polymers

Polystyrene
 Structural molecules
along the chains:
– Atactic molecules:
• Elements not all
facing the same way.
– Isotactic molecules:
• Elements are facing
atactic isotactic syndiotactic
same direction.
– Syndiotactic molecules:
• Elements alternate perfectly.

Polymers
 Effects of linearity, branching and symmetry on structure:
– Unbranched isotactic or syndiotactic polymers can
form highly crystalline denser materials.
– More branched, cross - linked or atactic chains form
amorphous, lower density materials.
 Degree of polymerization:
– The average number of monomers or repeating units
per molecule or chain.
– Longer chains result in less mobility of the polymer
– Higher molecular weight results in:
• Higher strength.
– More interweaving of the chains.
• Greater thermal stability.
Micro-structural levels in polymers
 Linear:
– No branches, most easily crystallizes.
 Branched:
– Single back-bone allows minimal
crystallization.
 Cross-linked or three dimensional network:

– Forms only amorphous structures.

Micro-structural levels in polymers
 Crystalline regions:
– Extended chains:
• Linear regions of chains.
– Folded chains:
• Chains wrapping
forth back and forth.
 Amorphous region:
– Totally random
structure.
 Fringed micelle:
– Coexistence of all three structures.

Surface properties
 The surface of the material should be fully characterized

in terms of its chemistry (elemental/molecular
composition), physical morphology, and structure.
 The interactions of macromolecules in the biological

system with the characterized surface should be studied.
 The cellular response to the material should be

evaluated by performing in vitro and in vivo experiments.

Surface characterization
 The surface will always be different than the bulk

material:
– Reactive to its environment
– Has reacted with its environment
– Has been modified during formation
– Contamination or impurities
– Forced atomic or molecular orientations
– Energy variations

Surface properties of materials

The surface region of a material is uniquely reactive.
unfullfilled valencies
– The surface is inevitably different
from the bulk.
– Surfaces readily contaminates.
– The surface structure of a material is often mobile (movement

of atoms and molecules near the surface).
hydroxylated polymer
The body „reads“ the surface structure of devices and

materials and responds.

 Implant surface
– Dense and inert:

• Implant movement and loosening is possible.
– Porous:
• Ingrowth of tissue (bone) stabilizes the implant.
• Blood supply is needed (pore size >100µm for
vascularization).
• Large porosity degrades strenght of the material.
• Micromovement of implant:
– Cut off of blood supply - tissue will die –
inflammation – interfacial stability will be
destroyed.

 Porous metals:
– Large increase of surface area provides focus for
corrosion of the implant and loss of metal ions into the
tissue.
• Surface coating with bioactive ceramic such as HA
(hydroxyapatite).
 Porous ceramics:
– Advant.: inert + bone ingrowth
– Disadvant.: weaker → restricted to non-load bearing
applications.

Surface characteization
 Interactions of macromolecules in the biological system

with the biomaterial:
– Reactivity
– Protein adhesion
– Absorption
– Permeability
– Corrosion
– Degradation

Surface characterization
 The cellular response to the material should be

evaluated by performing in vitro and in vivo experiments.
– Cell adhesion
– Cell motility
– Protein or enzyme production
– Gene expression
– Cell death or toxicity

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Institute for Genomics and Bioinformatics

Assoc. Prof. Dr. Juliane Bogner-Strauss

Vorlesungsunterlagen: IGB Homepage,

Biomaterials WS2008 Courtesy R. Zenz 1

A very short history of biomaterials

 The Romans, Chinese, and

 Glass eyes and wooden teeth

Biomaterials WS2008 Courtesy R. Zenz 2

A very short history of biomaterials

 Synthetic plastics became available at the turn of last

Biomaterials WS2008 Courtesy R. Zenz 3

Notable Developments Relating to Implants

Biomaterials WS2008 Courtesy R. Zenz 4

Various implants and devices for replacement or enhancement

Biomaterials WS2008 Courtesy R. Zenz 5

Biomaterial science - definitions

 Biocompatibility — The ability of a material to perform with an

 Host Response — The response of the host organism (local and

E.g.: A hemodialysis system serving as an artificial kidney requires

Biomaterials WS2008 Courtesy R. Zenz 6

Biomaterials WS2008 Courtesy R. Zenz 7

Examples of biomaterial applications (USA)

 Substitute heart valves (45,000/year)

Biomaterials WS2008 Courtesy R. Zenz 8

Examples of biomaterial applications (USA)

Biomaterials WS2008 Courtesy R. Zenz 9

Many materials are used

Biomaterials WS2008 Courtesy R. Zenz 10

Interdisciplinary interactions are needed

Different disciplines have to work

Biomaterials WS2008 Courtesy R. Zenz 11

Subjects integral to biomaterials science

Biomaterials WS2008 Courtesy R. Zenz 12

This information must be evaluated within the context of the

Biomaterials WS2008 Courtesy R. Zenz 13

Properties and structure

 Structure can be viewed at many levels:

 Each level of structure in a material affects the overall properties of

Biomaterials WS2008 Courtesy R. Zenz 14

Atomic or molecular level

– Almost all the physical properties depend on the nature and

Biomaterials WS2008 Courtesy R. Zenz 15

Bulk properties of materials

Solids are held together by strong interatomic forces.

Biomaterials WS2008 Courtesy R. Zenz 16

 Positively charged ion cores with negative electrons circulate around

 Allow plastic deformation electrons

 Good electrical and heat conductance

Biomaterials WS2008 Courtesy R. Zenz 17

 Formed between non-metallic atoms when the valence electrons are

 Poor electrical and heat conductance.

Biomaterials WS2008 Courtesy R. Zenz 18

 Metallic atom shares one or more electrons with the non-metallic

Biomaterials WS2008 Courtesy R. Zenz 19

Weak or secondary bonding

 Van Waals bonds:

 Hydrogen bonds Hydrogen bonds:

Biomaterials WS2008 Courtesy R. Zenz 20

Relative bond strenght