Additive manufacturing for biomedical applications

le centre collectif de l’industrie technologique belge

Additive Manufacturing for Biomedical applications

Grégory Nolens & Carsten Engel

Workshop, January 23th 2014

23/01/2014 © sirris 2012 Charleroi | www.sirris.be | [email protected] | 2

130 experts & high-tech infrastructure

Collective centre

of the technology industry

• Non profit organization

• Industry owned

4,700 industrial interventions

(advice, projects, services)

•within 1,700 different companies

•whose 75% are SME’s

•24M EUR turnover

Mission

“Increase the competitiveness of companies of

the Agoria sectors through technological

innovations”

3

Additive Manufacturing/3D Printing :

Basic Principles

Basic data :

Layer by layer manufacturing

3D CAD File 3D STL File Sliced File

Starting point:

3D CAD file

CENG

© sirris 2012 Charleroi | www.sirris.be | [email protected] | 23/01/2014

3D Printing – Next

• Obama said (feb. 2013): "A once-shuttered warehouse is

now a state-of-the art lab where new workers are mastering

the 3-D printing that has the potential to revolutionize the

way we make almost everything“

“We can’t wait” initiative


Fashion effect – public machine

• Design, gadget,

• but also functional and caring


Industrial and technical products

• Prototyping

• No assembly

• Personalized

• Technical

• Porous


23/01/2014 7

Additive Manufacturing : Basic Principles

Advantages of using AM … try something new !

• Low-cost ability to easily try out ideas generates many

innovations

• AM has seen children returning to making things. From

digital into reality.

• Testing the market with an idea with small production

• Alows inventors to realize their inventions and test

their market

© sirris 2012 Charleroi | www.sirris.be | [email protected] |

23/01/2014 8

Additive Manufacturing : challenges

Variety of materials still not vast enough

Lack of precision on some technologies

Machines still very pricy (industrial)

Need of certification and qualification of materials & process

Lack of surface quality and finishing

Not suited for big series (automobile)


9

Additive Manufacturing technologies @ Sirris

SIRRIS – European leader: Most complete machine park

• 15 engineers and technicians

• Two locations: Liège (10 p.) and Charleroi (5 p.)

Rapid Prototyping / Tooling / Manufacturing

• Stereolithography (normal & hi-res)

• Paste polymerisation for ceramics and metals (Optoform)

• 3D Printing of plaster and metal powder

• Laser sintering of polymeric powder (PA,…): P360 – P390

• Objet Connex 500: bi-material

• Laser sintering of metal powder (parts and mould inserts)

• Electron Beam Melting (Arcam A2)

• 3D Printing of wax (Thermojet)

• Vacuum Casting of Alu, Bronze, Zamak

• Laser Cladding (EasyClad)

• Selective Laser melting (MTT)

• Mcor - paper

• Bi-material FDM system

CENG


23/01/2014 10

Next generation pre-operative manufactured implants:

• Custom implant manufacture :

• CT-Scan

• CAD File of the patient is produced

• Engineer + Surgeon 3D implant approved

• FEM analysis (when needed)

• Custom manufacturing (low cost)

• Surgery

• Follow up


CENG

[Sirris ADD]

[Sirris ADD]

[Sirris ADD]

The utility of Additive Manufacturing technologies

in the medical field

11

Medical Additive Manufacturing Software:

ADD capacities & competencies

CENG

23/01/2014 © sirris 2012 Charleroi | www.sirris.be | [email protected] |

• Materialise: Mimics

• Materialise: 3matic

• Marcam: Autofab

• Able Software Corp: 3D Doctor

• Medicim: Maxilim

• ProEngineer

• New: Lenexa: Analyze

• New: Brisbane: Anatomics

• (…)

[Mimics & 3-matic - Materialise]

23/01/2014 12

Additive Manufacturing in the medical field

Leading applications:

• Custom implant manufacture (Scanning/Custom Prosthesis Design) • Pre-surgical planning • Physician to physician communication

• Powerful patient presentation tool

• Medical student/resident education


CENG

[Z. Corp Medical Modeling Solutions]

[Z. Corp Medical Modeling Solutions]

[Arcam & Objet technology]

[Sirris ADD]

23/01/2014 13


• Pre-surgical planning:

• Implant pre-contouring • Screw trajectory • Screw selection/location • Instrument selection • Technique rehearsal


CENG

[Objet]

[Objet]

[Objet Connex Eden 500]

[Objet]

“No matter how good our 3-D graphics are, there is

nothing like a model in your hands . . .”

The utility of Rapid Prototyping / Manufacturing in

the medical field

23/01/2014 14

Medical Field: CASE STUDIES @ SIRRIS


• Physician to physician communication

• Powerful patient presentation tool

• Medical student/resident education


CENG

[Sirris ADD] [Sirris ADD]

[Sirris ADD] [Sirris ADD] [Sirris ADD] [Sirris ADD]

23/01/2014 15



CENG

Spinal & CMF case studies in ceramic

• Porous scaffolds for Spine surgery

• In vivo testing for bone integration

• Validation production by Sirris Tech transfer

• Field: Maxillofacial Surgery in France, production in Belgium

[Sirris ADD]

[Sirris ADD] [Sirris ADD]

16

Medical field: Industrial Case studies


CENG

Project: “In vitro testing models - arteries”

• Goals:

• To gain biomechanical know-how

• Virtual prototyping, device testing, virtual design iterations

• Diagnostic research

• Technologies involved: Connex Eden 500 bi-material 3D inkjet printing

23/01/2014

23/01/2014 17



CENG

Surgical Cutting Templates

• UCL-St Luc (Belgium) • UCL spin-off: VISYOS • Polyamide cutting patient-custom cutting tools

• SLS technology + bio-coating

[VISYOS] [VISYOS]

23/01/2014 18



CENG

Surgical Cutting Templates – reimbursement problem

Surgical guides not reimbursed, but facts are:

- 1 min. in surgical theatre (estimated): 60€

- Mean of orthopedic surgery duration: 5-12h (18k-44k€)

- Surgical guide can reduce: 20-70% of the duration (TBC)

- Surgical guide cost: 50-300€

- Economy: estimated 3-30k€/surgery

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Medical Field: CASE STUDIES in the world


CENG

23/01/2014

[Dr J. Poukens – Uhasselt, Xilloc Medical (Maastricht)]

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World’s first total mandible implant in Titanium


CENG

23/01/2014

[UHasselt, Layerwise, Xilloc, Sirris, CamBioceramics, Orbis Medisch Centrum, Xios, KUL]

21 © sirris 2012 Charleroi | www.sirris.be | [email protected] |

CENG

Finger implant (Dr. P. Ledoux, Prof. G. Guerlement UMONS)

23/01/2014

Towards newly designed implants

[Université de Mons, Faculté Polytechnique]

22 © sirris 2012 Charleroi | www.sirris.be | [email protected] |

CENG

23/01/2014

The future of bio-manufacturing…not so far away!

23

process of printing biologically relevant materials (such as cells,

tissues, and biodegradable biomaterials) that will accomplish

one or more biological functions

What’s Bioprinting


+

cells

Bio-glue

3D machine

Tissues/organs Scaffolds

+ cells

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=cxH1DMQortvt7M&tbnid=ZwgRtPf3evz6tM:&ved=0CAUQjRw&url=http://www.bronzedgoddess.net/product_info.php?products_id=1162&ei=tH_lUfTXO4LOONPtgIgN&bvm=bv.48705608,d.ZWU&psig=AFQjCNFW3GrA6CC31-td7WH9EG5reG-zmw&ust=1374081281698211

http://www.google.com/url?sa=i&source=images&cd=&cad=rja&docid=10PQMU3M_mq11M&tbnid=hWy3pekOaoSwQM:&ved=0CAgQjRwwAA&url=http://www.gizmag.com/3d-bio-printer/13609/&ei=xoHlUbrlMsfXPYbCgMAM&psig=AFQjCNGGQYuzBjhWM8FRWq3HMXx4Xpsk6A&ust=1374081862876612

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=3mtWJSsTB0ClHM&tbnid=x0QrSPNVN0ApGM:&ved=0CAUQjRw&url=http://galanx-ragalofo.blogspot.com/&ei=MoLlUe2fF4LvPJq4gYgL&bvm=bv.48705608,d.ZWU&psig=AFQjCNHW_RxCUx6l23mKZN99a4qHepoknQ&ust=1374081947300638

23/01/2014 24 © sirris 2012 Charleroi | www.sirris.be | [email protected] |

Bioprinting – an emerging technology

Bioprinting place in emerging technologies, from the Hype Cycle for Emerging

Technologies 2013- Gartner

25

Market approach interest for companies?


• Applications:

• Drug discovery & Assays

• Cell therapy + Tissue Engineering

• Bioprocess

• In vitro diagnostic & research

• Food

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Drug Discovery and Assays


• Facts: Drug Discovery and Assays

• 90-95% of drugs approved on animal (mouse, rabbit, etc.), was not

for human lot of money lost, ethic problem

• Animal use: 10-100 Mio in US/year

• European Comission banning: FULL on cosmetic (2013), next

pharma (?)

27



• Applications:

• Drug screening w/o animal

& less deviations

Pharmaceutical area

Drug X

Disease tissue

Treated tissue

Organovo’s targeted market

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=KPRYyTyQFzdamM&tbnid=m1dCSKaIGnNk5M:&ved=0CAUQjRw&url=http://www.express.be/business/fr/management/franois-fornieri-administrateur-delegu-de-mithra-pharmaceuticals-dsign-manager-de-lanne-2011/160098.htm&ei=sZv3UebAPMnvPPTTgegP&bvm=bv.49967636,d.ZWU&psig=AFQjCNEYNogo77cgcfMFj6aABkYcDLiL8g&ust=1375268142327342

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=JWu5qO4rBz901M&tbnid=LYsvkTyLyjb1pM:&ved=0CAUQjRw&url=http://www.henogen.com/default.htm&ei=WZ33UfL3H4SrPLikgOgO&bvm=bv.49967636,d.ZWU&psig=AFQjCNHnsYnxY2C1cd9SnM3GX_TmxOQ7dw&ust=1375268532957151

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Cell Therapy & Tissue engineering


• Facts: Tissue engineering

• Alternative to donor waiting list

• Limited available « material » resource (skin, organs, cells, …)

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• Facts: Cell Therapy

Cell therapy industry market

(2008–2014).

Graph showing the estimated

CTI revenues from 2008–2014

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• Facts: Cell Therapy

High potential for

Small defect repair

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• Applications:

• Large defect repair

https://www.google.com/imgres?imgurl&imgrefurl=http://www.jobday-sciences.be/etud/societes.php&h=0&w=0&sz=1&tbnid=77GpH4B6V0iQnM&tbnh=94&tbnw=538&zoom=1&docid=WIw11yLmqf7nQM&hl=fr&ei=jKL3UeGiBIPfOIHVgbgN&ved=0CAEQsCU

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=IF3LJs0QtJqT8M&tbnid=fgqO7NZrmbC-PM:&ved=0CAUQjRw&url=http://www.animationeconomique.be/?p=2231&ei=O6P3UcuDOsbXPLDqgNAK&bvm=bv.49967636,d.ZWU&psig=AFQjCNGEjU9fmCn_-cAgH9eCjUFcbmHtPA&ust=1375270073987751

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• Applications:

• Biocompatibility assays w/o animals (ISO)

Artificial skin Irritation

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=bj5pM1_6XosHfM&tbnid=qLm5Bh3kmROUSM:&ved=0CAUQjRw&url=http://www.nu-age.eu/Partners/p2&ei=sZ33UazMAsfsPI2pgTg&bvm=bv.49967636,d.ZWU&psig=AFQjCNH9z1AbpwRKOhGmdqBJKuk8IJ6IUQ&ust=1375268653224537

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=fO260quefFAQ8M&tbnid=GiyuNbC506nWCM:&ved=0CAUQjRw&url=http://www.oceanridgebio.com/about-us.html&ei=z533Ud_DGojgOsO6gTg&bvm=bv.49967636,d.ZWU&psig=AFQjCNFzt2bLAntwhUKwMJ7vfPeRTr38SQ&ust=1375268683938946

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=U3iGDb3pncH0XM&tbnid=4LY3rV93QWzIAM:&ved=0CAUQjRw&url=http://ltvidar.blogspot.com/2012/12/sgs-mauritanie-un-oublie-de-laperation.html&ei=-p33UbL1B4fFPaiDgXg&bvm=bv.49967636,d.ZWU&psig=AFQjCNFeBd2pROfrAvNuvOG21KqdxZvE7g&ust=1375268724681978

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Technological approach


• Applications:

• In vitro diag and Research

• Biomarker

• Drug kinetic

• Pathogen reaction

//upload.wikimedia.org/wikipedia/commons/1/12/Blood_vessels_brain_english.jpg

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=d7pRvhKiL1Aa9M&tbnid=abEEmHzbxQ_V_M:&ved=0CAUQjRw&url=http://www.bcru.ulg.ac.be/accueil.html&ei=HaH3UcqcCsbNOI2bgMgD&bvm=bv.49967636,d.ZWU&psig=AFQjCNFv0NeEBu1cJi9AcPcMfjZNmmKXGg&ust=1375269530382735

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=wzJEO5Ba7nb4JM&tbnid=oTNeAoO87lOT3M:&ved=0CAUQjRw&url=http://www.biophare.eu/biophare-accueil-chercheur-demploi/index.html&ei=PqH3UazdL4HsPLvSgJgO&bvm=bv.49967636,d.ZWU&psig=AFQjCNHiN9f9B2EZC5iAPFsEOfR2P-Ux1A&ust=1375269564457142

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=IpgaF_I3SqKBGM&tbnid=HCzt6SDGzEQcRM:&ved=0CAUQjRw&url=http://www.stratex.be/nl/references/&ei=M6z3UbKeAYHEPPDmgJAE&bvm=bv.49967636,d.ZWU&psig=AFQjCNHaPTynD-UofCTSq1ItpsYac1kKzQ&ust=1375272348729772

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Biotechnolgies & Bioprocess


• Applications:

• Biomolecule production in 3D

• Machine producers

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=WHmxuGaIo1AtGM&tbnid=kKsje8783pOivM:&ved=0CAUQjRw&url=http://www.mypharma-editions.com/delphi-genetics-accorde-une-licence-a-sanofi-pasteur-pour-la-production-sans-antibiotique-de-vaccins-humain&ei=uav3Uaq2IYu9PfSpgOAF&bvm=bv.49967636,d.ZWU&psig=AFQjCNGSpfEi77rkBxQOIvb-vWzBXHsV7w&ust=1375272247800235

http://www.progenosis.com/

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Food & Agriculture


• Applications:

• New food process?

Focus on food player with Life

Science approach: biomaterial

( e.g. Tissue engineering)

Bioprinting

• Where beginning R&D?


Tissue engineering basics

• Lamarck (1744–1829): La fonction crée l’organe

(The function creates the organ).



• Lamarck (1744–1829): the function creates the organ.

daylife example: tissue reacts to device


« 2nd skin » development


• One scaffold can be enough


Tube with structure mimicking vascular matrix Rat implantation

Cell infiltration differentiation scaffold disapear tissue restorated


Scaffolds + stem cells + growth factors = work better


Artificial heart tissue (Taylor, Minnesota, 2009)

Artificial kidney tissue

Scaffolds come from animal washed for cells

3D Bioprinting solutions


Personalized

scaffolds

incubation with

stem cells

IPL, UGent, …



Nanostructure for

fluidic, cell interaction,

scaffold,…

2PP (two photon

polymerisation)

Very small devices

Nanoscribe



Industrial machines

Personalized

scaffolds

incubation with

stem cells

(and cell printing)

EnvisionTech, GESIM, Regenovo (China)…



Personalized

scaffolds +

stem cells

incubation

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=PG6biFQqEB_i0M&tbnid=A3VC-_idTQH1EM:&ved=0CAUQjRw&url=http://www.mfoundation.org/blog/2012/02/organovo-named-one-of-fifty-most-innovative-companies-of-2012/&ei=a233UfWrK8iaO8bWgMgN&bvm=bv.49967636,d.ZWU&psig=AFQjCNGmesoN7lbj3KhPqFGCqRXLLojTJQ&ust=1375256270570579

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=sV71q8JOl-sQUM&tbnid=JHixEv8U19W8qM:&ved=0CAUQjRw&url=http://www.about3dprinters.com/3d-printing-companies.html&ei=Qm73UePfFoO-O621gPAI&bvm=bv.49967636,d.ZWU&psig=AFQjCNGKqYjyFelvFUIaRvxq9NZdyKsCyQ&ust=1375256511808716

Bioprinting players in the world


• Keyplayers outside Europe

• Dr. Shinya Yamanaka (JPUS): stem cells

• Dr. Anthony Atala (US, Boston)

• Wake Forest University (US, North Carolina)

• ACES (Australia) biopen

• China

Bioprinting players in Europe – few


http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=zb3LM3dC1-SnKM&tbnid=WG4Cb3I3ugyTOM:&ved=0CAUQjRw&url=http://www.filkfreiberg.de/en/&ei=wmvAUcX7HeGQ0QXUo4DoCw&bvm=bv.47883778,d.d2k&psig=AFQjCNGS3MY9dWHOF9OSeJOlCwmrGbJ_rg&ust=1371651388198460

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=zb3LM3dC1-SnKM&tbnid=WG4Cb3I3ugyTOM:&ved=0CAUQjRw&url=http://www.filkfreiberg.de/en/&ei=wmvAUcX7HeGQ0QXUo4DoCw&bvm=bv.47883778,d.d2k&psig=AFQjCNGS3MY9dWHOF9OSeJOlCwmrGbJ_rg&ust=1371651388198460

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CENG

« Medical Additive Manufacturing & Rapid Prototyping »

« Sirris »


48

Sirris Additive Manufacturing: Contact


CENG

23/01/2014

Carsten ENGEL, Ir, MBA

Department of Additive Manufacturing

Mail: [email protected]

Mobile: +32 498 91 94 50

Skype: Carsten-Engel

SIRRIS

Rue Auguste Piccard, 20

B-6041 GOSSELIES BELGIUM

http://www.sirris.be

Grégory NOLENS, PhD

Department of Additive Manufacturing

Mail: [email protected]

Mobile: +32 498 91 94 75

Skype: gnolens

SIRRIS

Rue Auguste Piccard, 20

B-6041 GOSSELIES BELGIUM

http://www.sirris.be

Additive manufacturing for biomedical applications

Technology

rue auguste

custom implant

medical studentresident

tissue engineering

3d bioprinting

cell therapy

cell therapy

tissue engineering