Action MP1005

From nano to macro biomaterials (design, processing,

characterization, modeling) and applications to stem cells
regenerative orthopedic and dental medicine (NAMABIO)

Nata!a Drnov!ek, Sa!a Novak

Jo"ef Stefan Institute
Ljubljana, Slovenia

Training School, Zagreb, 26-29 April 2014

Further interests

Regards from Ljubljana

1. Classification of biomaterials:
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General introduction
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Classification of biomaterials
Relevant properties

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Types of biomaterials

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Tayloring the properties

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2. Processing of bulk implants and coatings

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Introduction in colloidal and surface chemistry, electrophoretic deposition,
sol-gel, Hydrothermal treatment
!!
!!

Deposition of coatings
Case studies: TiO2, PEEK, bioactive glass coatings, antibacterial coatings;

3. Processing of scaffolds
!!

Basic requirements for the scaffolds; shaping techniques; issues; ..

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Action MP1005

From nano to macro biomaterials (design, processing,

characterization, modeling) and applications to stem cells
regenerative orthopedic and dental medicine (NAMABIO)

Training School, Zagreb, 26-29 April 2014

What are "biomaterials?!

Non-viable materials used in medical devices intended to interact with

biological systems" (D. F. Wiliams, 1987)
Applications
"!

Dental implant

"!

Joint prosthesis

"!

Bone plates

"!

Bone fixing screws, suture

"!

Bone defect fillings

"!

Vascular implants

"!

Scaffolds for tissue engineering

"!

Contact lens

"!

Dental fillings

"!

Earings, piercing,..
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"!

1st Generation (>Y.1950): Boinertness

"!

2nd Genertion (>Y.1980): Bioactivity/biocompatibility

"!

3rd Generation (>2000): Tissue regeneration (cell and gene activation)

Bone is the second transplanted tissue after

blood (UK) http://www.slideshare.net/Maxisurgeon/downloadbiomaterials-powerpoint

Vitalium:Co-Cr-Mo
alloy

by source
"! natural
!! Autograft - autologous (or autogenous): bone obtained from the same
individual receiving the graft
!! Allograft: harvested from an individual other than the one receiving the
graft
!! Xenografts: origin from a species other than human (e.g. bovine,
wood)
"! synthetic
by biological role
"! toxic
"! bioinert: does not interact with the body
"! bioactive: actively participate in tissue repair
"! bioresorbable: resorb and provide elements for the tissue repair
by the function (duration of use)
"! Temporary
!! Non-resorbable support to be removed
!! biodegradable support - scaffold
"! Permanent

by composition
"! Metals & alloys
"! Polymers
"! Ceramic, glass, glass-ceramic
"! Natural materials (from plants and animals)
by structure
"! bulk
!! stems, plates, screws, pins, ...
"! coatings
!! protective
!! bioactive (HA, BAG)
"! porous
!! porous metallic surface layer
!! scaffolds for tissue engineering

!!

high loads (orthopaedic, dental, ....) " How high?

!!

high wear (joints) " effects of wear particles!

!!

corrosion in biological environment (even Ti)

(osteoclasts enhanced corrosion, ion release 1)

!!

resorption " kinetics!

!!

long terms....! " tests are typically short terms!

1D.

Cadosch, et al, Biocorrosion and uptake of titanium by human osteoclasts, JOURNAL OF

BIOMEDICAL MATERIALS RESEARCH A | 15 DEC 2010, 95A, ISSUE 4

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Biological (short and long term)

"! toxicity (cito-, geno-, immuno-)
"! antibacterial/bactericide effect
"! Interaction with biomolecules (blood cells, proteins, .....)
Structural
"! architecture
"! pore size and connectivity
Physical
"! Contact angle (hydrophilicity / hydrophobicity)
"! magnetic properties
"! visibility by X-ray
"! Photoactivity
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Chemical
"! corrosion resistance (Metals)
"! solubility and pH under physiological conditions:
Gastric content 1.0
Urine
4.5-6.0
Intracellular
6.8
Interstitial
7.0
Blood
7.17-7.35
"! ability for mineral bone (HA) formation
"! Polymers: molecular weight
Mechanical
"! "flexibility" (elastic modulus)
"! strength (compressive, shear, adhesion,..)
"! viscoelastic properties (soft scaffolds)

In long terms in vivo (10, 20, 30 years)!!

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Can we overcome the issues by adaptation using suitable processing?

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Metals for implants:

"!

Stainless steel

Co-Cr alloys
"! Ti and Ti-based alloys
"!

"!

!-Ti

"!

Ni-Ti (shape memory!)

"!

Mg-alloys

"!

Oxinium (oxidized Zr-alloy)

"!

Au-Ag-Cu-Pd alloys (dental)

"!

Amalgam (AgSnCuZnHg)

Advantages
High strength
Fatigue resistance
Relatively good wear resistance
Easy fabrication
Easy to sterilize
Shape memory (NiTi-Nitinol)
Issues
High elastic modulus
Corrosion - Metallosis
Metal ion sensitivity and toxicity
Low wetting

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Polymers
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!!
!!
!!
!!
!!
!!
!!
!!
!!
!!
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PMMA
PVC
PLA/PGA
PE
PP
PA
PTFE
PET
PEG/PEO(water soluble)
PEEK
Silicones
Natural polymers:

Advantages
Easy to make complicated items
Tailorable physical & mechanical
properties
Surface modification
Biodegradable (some)
Issues
Leachable compounds
Absorb water & proteins etc.
Surface contamination
Wear & breakdown
Biodegradation (hydrolytically, encimatically)
Difficult to sterilize

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Ceramics, glass, glass-ceramics

"!
"!
"!
"!

Alumina (Al2O3)
Zirconia (ZrO2)
Non-oxide (SiC, Si3N4)
(HAp, Ca-P)

Advantages
High compression strength
Wear & Corrosion resistance
Can be highly polished
Bioactive/Inert
Issues
High E modulus (stress
shielding)
Brittle -Low fracture toughness
Difficult to fabricate

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Ceramics, glass, glass-ceramics

Advantages

Ca-phosphates, TCP
Hydroxyapatite (Ca10(PO4)6(OH)2
Ca-carbonate
Wollastonite (CaSiO3)

Bioactive glasses
SiO2-CaO-P2O5-MxOy..

Composition similar to bone

Relatively good osseointegration
Biodegradable (slow, partly)
Issues
Biodegradable
Brittle
Advantages
Si/Ca - stimulative for osteoblasts,
proliferation and differentiation
Higher reactivity and faster
osseointegration
Biodegradable (can be taylored)
Bioactive
Issues
Biodegradable
Brittle!!!
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Consider a timescale of the implant being in the

body
months, years,
!!

!!

decades

The mechanical properties of the material may

change (also those for the natural bone do!)
Ions are released from the materials (may
cause inflammation and adverse health
effects)

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250

E (GPa)

Too high elastic modulus (Stress

shielding)
"!
Porosity lowers the E-modulus
(but pay attention to strenght)

200
150
100
50
0

Brittleness:
"!
Reinforcement by particles
(e.g. ZrO2 in Al2O3 ceramics)
or by fibers

Zirconia
0

20

40
60
Porosity (%)

80

100

50% gellan gum + 50% BAG

A. Gantar, .....
A. Gantar, IJS 19

Corrosion, metal ions release

protective coating, avoiding toxic
elements

Hydrophobicity
etching, photocatalitic coating

Cell attachment
roughnening

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HA formation
Highly bioactive coating (BAG)
Tailoring the roughness
Tailoring the surface chemistry
(surface charge, OH or COOH-)

Enhanced HA formation on Ti 21
by
NaOH

Protein attachements
Surface charge, hidrophilicity,
irradiation
Cell attachment
Bioactive coatings
Surface charge modification
Hydrophilicity
Inflammation
Antibacterial or bactericidal coating
Avoiding toxic and allergenic elements
Hydrophobicity

Day 3

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! There is no ideal synthetic biomaterial

! A good balance between the
advantages and issues is needed

(not on account of adverse biological response!)

A good design "MAKE YOUR OWN

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Designers sometimes feel this way#

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An exercise in biomaterials design:

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Select an implant

!!

Define the relevant properties

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Define the material

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Propose the processing technique

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For what application could it be used

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But you have to use the proper material and design it properly!

Hey, lets have a

break and think
about it again!

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# - good
$ - bad
% - neutral

Wear
parts
joints

Load-bearing parts
stems, plates,
screws

Defect fillers

dental posts

scaffolds
N/A

cyto-, geno-, immounotoxic

ions, electrocorrosion
(galvanic cells) delayed
effects

N/A

Al2O3: Al3+, brittleness

ZrO2: hydrothermal
degradation, Zr4+, Y3+
SiC: processing, brittleness

N/A

biodegradable
osseoconductive
ion release
strength

limited to coating and fillers

wear
strength
ion release
(catalysts)

strength
osseointegration

biodegradable

PDLLA
PEEK
..

N/A

BAG-coated metal

BAG-polymer

mechanical properties
degradation rate

Metals,
alloys

strength
wear
corrosion
dissolution
(metal release)

Ceramics
(Al2O3,
ZrO2)

strength
wear
corrosion
dissolution
(metal release)

Bioactive
glasses

strength

Polymers,
biopolymers

composites

strength
corrosion,
dissolution (metal release)
osseointegration (wetting, surface charge)

Issues to be
considered

strength
corrosion
dissolution (metal
release)
osseointegration

Grrard Eddy Jai Poinern, American

Journal of Biomedical Engineering,
2013; 3(6): 148-168

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