Training School, Zagreb, 26-29 April 2014 1

Nata!a Drnov!ek, Sa!a Novak Jo"ef Stefan Institute Ljubljana, Slovenia

From nano to macro biomaterials (design, processing, characterization, modeling) and applications to stem cells regenerative orthopedic and dental medicine (NAMABIO) Action MP1005

Further interests

Regards from Ljubljana

1. Classification of biomaterials: !! General introduction !! Classification of biomaterials !! Relevant properties !! Types of biomaterials !! Tayloring the properties

2. Processing of bulk implants and coatings !! 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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From nano to macro biomaterials (design, processing, characterization, modeling) and applications to stem cells regenerative orthopedic and dental medicine (NAMABIO) Action MP1005

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)

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Bone is the second transplanted tissue after blood (UK) http://www.slideshare.net/Maxisurgeon/download-biomaterials-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

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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

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!! 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!

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1D. Cadosch, et al, Biocorrosion and uptake of titanium by human osteoclasts, JOURNAL OF BIOMEDICAL MATERIALS RESEARCH A | 15 DEC 2010, 95A, ISSUE 4

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)

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

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)

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High elastic modulus Corrosion - Metallosis Metal ion sensitivity and toxicity Low wetting

High strength Fatigue resistance Relatively good wear resistance Easy fabrication Easy to sterilize Shape memory (NiTi-Nitinol)

Issues

Advantages

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

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Leachable compounds Absorb water & proteins etc. Surface contamination Wear & breakdown Biodegradation (hydrolytically, encimatically) Difficult to sterilize

Easy to make complicated items Tailorable physical & mechanical properties Surface modification Biodegradable (some)

Advantages

Issues

Ceramics, glass, glass-ceramics

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

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High compression strength Wear & Corrosion resistance Can be highly polished Bioactive/Inert

High E modulus (stress shielding) Brittle -Low fracture toughness Difficult to fabricate

Advantages

Issues

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Composition similar to bone Relatively good osseointegration Biodegradable (slow, partly)

Biodegradable Brittle

Advantages

Issues

Ca-phosphates, TCP Hydroxyapatite (Ca10(PO4)6(OH)2 Ca-carbonate Wollastonite (CaSiO3) Bioactive glasses SiO2-CaO-P2O5-MxOy..

Ceramics, glass, glass-ceramics

Si/Ca - stimulative for osteoblasts, proliferation and differentiation Higher reactivity and faster osseointegration Biodegradable (can be taylored) Bioactive

Biodegradable Brittle!!!

Advantages

Issues

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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Too high elastic modulus (Stress shielding) "! Porosity lowers the E-modulus (but pay attention to strenght) Brittleness: "! Reinforcement by particles

(e.g. ZrO2 in Al2O3 ceramics) or by fibers

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0

50

100

150

200

250

0 20 40 60 80 100

E (G

Pa)

Porosity (%)

Zirconia

A. Gantar, .....

50% gellan gum + 50% BAG

A. Gantar, IJS

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-)

21 Enhanced HA formation on Ti 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

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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#

An exercise in biomaterials design:

!! Select an implant

!! Define the relevant properties

!! Define the material

!! Propose the processing technique

!! For what application could it be used

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

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Hey, let‘s have a break and think about it again!

Wear parts

Load-bearing parts Defect fillers Issues to be considered

joints stems, plates, screws

dental posts

scaffolds

Metals, alloys

strength wear corrosion dissolution (metal release)

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

N/A cyto-, geno-, immounotoxic ions, electrocorrosion (galvanic cells) – delayed effects

Ceramics (Al2O3, ZrO2)

strength wear corrosion dissolution (metal release)

strength corrosion dissolution (metal release) osseointegration

N/A Al2O3: Al3+, brittleness ZrO2: hydrothermal degradation, Zr4+, Y3+ SiC: processing, brittleness

Bioactive glasses

strength N/A biodegradable osseoconductive ion release strength

limited to coating and fillers

Polymers, biopolymers

wear strength ion release (catalysts)

strength osseointegration

biodegradable

PDLLA PEEK …..

composites N/A BAG-coated metal BAG-polymer mechanical properties degradation rate

# - good $ - bad % - neutral

Gérrard Eddy Jai Poinern, American Journal of Biomedical Engineering,

2013; 3(6): 148-168 28