BioresorbableMagnesium Alloys for Orthopaedic Trauma Surgery · - Magnesium Elektron (materials development and ... studies are warranted with a purer ingot of this material. •

David J. Browne

Professor, Materials Science and Engineering

Vice-Principal for Research, Innovation & Impact

College of Engineering & Architecture

School of Mechanical & Materials Engineering

University College Dublin

Ireland

Bioresorbable Magnesium Alloys for Orthopaedic

Trauma Surgery

MedTecGalway

4-5 October 2017

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Selected Extracts from Presentation

• The full presentation was delivered at the meeting in Galway on Wednesday afternoon, 4 October 2017.

• Some content, including illustrations, and unpublished results, is removed here due to confidentiality and copyright concerns.

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Outline of Presentation

• the Problem

• the Conventional Solution

• the Problem with the Conventional Solution

• the New Solution - conventional new solution

- novel new solution

• Outlook and remaining challenges

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The Problem

• Bone Fracture

• Healing

• Support

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The Conventional Solution

• Biomedical Implants

• Metallic Plates, screws, pins

• Materials: stainless steel, titanium alloys (Ti-6-4)

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Problems with Conventional Solution

• Appropriate mechanical properties – sy

– E

• Corrosion and fatigue

• Built-in redundancy

• Chronic pain; patient discomfort

• Removal surgery – difficulty, additional trauma, risk of infection

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The New Solution - conventional

• Biodegradable metallic devices

• Mg-based

• Mg in the body; dissolution

• Other alloying elements

• Y, RE, Zr

• Ca and Zn

• Corrosion rate

• H2 evolution

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The New Solution in practice

Property Matching

Properties Cortical bone MgZnCa BMGsCrystalline Mg

alloysTi-6Al-4V Stainless Steel

Synthetic

Hydroxyapatite

Density (g/cm3) 1.8-2.1 2.0-2.8 1.74-2.2 4.4-4.5 7.9-8.1 3.1

Elastic Modulus (GPa) 3-30 22-50 41-45 110-117 189-205 73-117

Compressive Yield Strength (MPa) 130-180 400-1190 100-560 758-1117 170-310 600

Fracture Toughness (MPa1/2) 3-6 NA NA 55-115 50-200 0.7

Meagher, P. et al.,

Adv. Mater., 28, 2016, 5755-5762Recommended adult allowances (mg/day):

Mg: 420

Ca: 1000

Zn: 10

Approx. 25g of Mg naturally present in adults.

Mg helps bone growth, inhibits inflammation

and prevents clot formation.

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The New Solution – practice and problems

• Industry uptake

- Syntellix (device design and manufacture) Magnezix®

- Magnesium Elektron (materials development and supply) SynerMag®

• Current clinical situation: Germany, Korea, China

• Problem with corrosion rate

• Mg + 2H2O → Mg(OH)2 + H2 (gas)

• Excessive hydrogen evolution: sub-cutaneous bubbles

• Excessive mineral supply rate (Mg, Ca, Zn)

• Bone not healed by the time implant loses strength

• Need a more corrosion-resistant material

• Novel solution: bulk metallic glass

Metallic Glass = Amorphous Metal

Ref: Maukawa, E. et al., J. Biomed. Mater. Res., 104B, 2016, 1282-1289

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• Hard

• Strong

• Wear resistant

• Corrosion resistant (zero microstructure)

• Biocompatible

• High precision replication – sharpness

• Tough in micro-parts

100 mm

Bulk (>1 mm) amorphous metal = bulk metallic glass

Mg-22Zn-5Ca can be produced in both crystalline and

glassy forms

The New Solution - novel

Amorphous Metal Properties

Corrosion comparison

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5 mm

5 mm

10 mm f crystalline samples

after 10 days in DMEM

Samples immersed in DMEM for indirect and direct cellular response testing, and observation of alloy corrosion.

Immersion in DMEM for 24 h, at 37 oC, and 5% CO2 to form an elution medium.

Medium transferred to wells containing healthy human dermal fibroblasts.

The cells were cultured for 24 and 48 h for indirect exposure. The samples were transferred to separate wells for 24 and 48 h direct cell exposure.

Total 3 mm f sample time in DMEM: 48h, 72 h.

BMG

Crystalline

48 h 72 h

Byrne, J. et al.,

European Cells and Materials, 30 (3), 2015, 75

Cytotoxicity comparison

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5 mm

CytoTox 96® assay on 24 h samples, measures the release of lactate dehydrogenase (LDH) signallingthe loss of membrane integrity and thus levels of cell death.

Copper and stainless steel coupons, of the same size, had been used as controls.

There was little significant difference in cytoxicity (direct or indirect) between conventional and metallic glass Mg alloy after 24 h.

The alloy contained trace elements, including rare earths.

Byrne, J. et al.,

European Cells and Materials, 30 (3), 2015, 75

Conclusions of initial study

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5 mm

• A pre-alloyed Mg-Zn-Ca alloy was cast in amorphous form relatively easily, and exhibited a critical casting diameter of 3 mm.

• The original crystalline variant of the alloy corroded significantly faster than the metallic glass.

• The crystalline structure of the Mg alloy does not impact on relative cytotoxicity, however further studies are warranted with a purer ingot of this material.

• Composition of the alloy for the initial investigation was chosen because of its glass forming ability

• This is not typical of commercial (crystalline) Mg alloys

• Following work included comparison of the Bulk Metallic Glass alloy with a biomedical grade crystalline alloy (WE43).

Conventional Mg biomedical alloy

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5 mm

• Further work was required to compare the BMG with a commercial Mg alloy

• Corrosion under stress also relevant

• WE 43 was chosen. Aluminium-free casting alloy being investigated as implant material.

Results yet to be published.

Outlook and Challenges

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5 mm

For their many advantages, the use of Mg alloys in orthopaedic surgery will

continue to grow.

Alloy composition remains to be optimised (for both C and A forms).

Improved understanding is needed of:

- Strength and ductility

- Cytotoxicity

- Fatigue

- Corrosion/resorption

- In vivo behaviour

- Manufacturing processes (incl. additive) §

Li, J. et al.,

Chem. Commun., 53, 2017, 8288-8291

§ www.I-Form.ie

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END

to co-workers at UCD:

Dr Eoin O Cearbhaill, Assistant Professor

Students

James Byrne

Garvan Keenan

Philip Meagher