3D-Bioprinting:Applications for Medicine and

TechnologyBruce Reimer

CEO and President, Strategic 3D Solutions

Rahul Roy

Support and Applications Engineer, EnvisionTEC Inc.

April 4, 2017

Agenda

• Introduction

• Purpose of Bioprinting

• Applications and Materials

• Construction

• Case Studies

• EnvisionTEC’s Bioplotters

• Q&A

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3D Printers 3D Scanners 3D Printing

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Product Families

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Product Families

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Bioprinting: From Construct to Tissue• Raw materials converted to constructs, layer-by-layer

• Four major applications:• Drug-delivery testing

• In-patient tissue regeneration

• Cell differentiation studies

• Pathology

Raw material Scaffold Tissue

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Construct Considerations

• Inducing Tissue Regeneration

• Biocompatibility

• Biomimicry

• Degradability

• Vascularization

• Neurogenesis

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• Combine and adapt existing biomaterials to mimic tissue

• Hard Materials:◦ Thermoplastics – PLGA, PLLA, PCL◦ Ceramics – β-TCP, hydroxyapatite◦ Metals – Ti-6Al-4V (not for degradation)

• Soft Materials:• Synthetic Hydrogels – PEG, PVA, PGS• Natural Hydrogels – Collagen, Agar, Hyaluronic Acid

Many Applications, Many Biomaterials

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Thermoplastic Solidification

• Thermoplastics liquefy at a working temperature, much higher than melting temperature, and rapidly cool to solidify.

• Using the 3D-Bioplotter, other materials can be blended to achieve different physical and mechanical properties.• Other thermoplastics

• Ceramics

• Graphene

• Other temperature withstanding substancesΔH

120°C

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Hydrogel Cross-linking and Crystallization

• UV-cross linking

• Chemical reaction

• Rapid cooling

• Freeze-drying

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Metal and Ceramic Sintering

• Metal powders can be suspended in a binder. The printed object is a weak construct called a green body.

• An oven can be used to burn away the binder and melt the particles together.

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Inner Structures Determine Mechanical Properties

Side view: 1 mm spacing, 90° alignment Side view: 1 mm spacing, 90° alignment0.5 mm shift

Top view: 1 mm spacing, 90° alignment Side view: 1 mm spacing, 45° alignment 12

Sustained Delivery of Tuberculosis Drugs

• Authors: Yuan, Jing; Zhen, Ping; et al.

• Material:• Ceramic - β-TCP

• Loaded with tuberculosis drugs and examined degradation rate/release

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Fiber Reinforced Hydrogel Composites

• Authors: Bakarich, Shannon; Gorkin, Rober; et al.

• Materials:• Hydrogel - Alginate ICE, Emax 904 Gel Adhesive, Alginate Support Gel

• Additional UV curing step

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Application: Knee meniscus production

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Protein releasing scaffolds for knee meniscus regeneration in sheep• Authors: Lee, Chang Hun; Rodeo, Scott A.; Fortier, Lisa Ann; Lu,

Chuannyong; Mao, Jeremy J.

Materials: ◦ Thermoplastic – PCL

◦ Ceramic - TGF-β3

different spatially distributed factors:• CTGF – bone marrow cells to fibroblasts

• TGF-β3 – cell adhesion, ECM formation

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Regeneration of Periodontium Complex• Authors: Lee, Chang Hun; Hajibendeh, Jefferey;

Suzuki, Takahiro; Fan, Andrew; Peng, Shang; Mao, Jeremy J.

• Materials: • Thermoplastic - PCL• Ceramic - Hydroxylapatite

• Three different time-release factors• Amelogenin – dentin/cementum formation • CTGF – bone marrow cells to fibroblasts• BMP2 – alveolar bone regeneration

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Significant Cell Growth and Differentiation

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Sr-MBG Scaffolds for Rat Calvarial Defects

• Authors: Zhao, Shichang; Jianhua, Zhang; et al.

• Materials: Sr-MBG

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Significant Vascularization and Regeneration

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Metallic Architectures from 3D-Printed Powder-Based Liquid Inks• Authors: Jakus, Adam; Taylor, Shannon L.; Geisendorfer, Nicholas R.;

Dunand, David C.; Shah, Ramille N.

• Materials: PLGA, solvents, various powders including hydroxyapatite, graphene, metal oxides,

Using solvents and PLA as a stronger, faster printing binder for any number of powders.

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Clinical Bioprinting is on the Horizon• Bioprinting has shown great promise in labs as a real solution for:

• Understanding how we develop

• Therapies better tailored towards the individual

• Faster recovery time

• Less invasive procedures

• With continued in vivo and in vitro studies, we can look forward to:• Full organ printing

• Surgeries with minimal recovery time and no rejection

• The next-generation of pharmaceuticals

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3D-Bioplotters

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Highlights Enhancements

Compared to Developer

Highlights Enhancements

Compared to Starter

Starter Series Developer Series Manufacturer Series

Axis Resolution (XYZ) 0.001 mm (0.00004”) 0.001 mm (0.00004”) 0.001 mm (0.00004”)

Speed 0.1 - 150 mm/s (0.004” - 5.91”/s) 0.1 - 150 mm/s (0.004” - 5.91”/s) 0.1 - 150 mm/s (0.004” - 5.91”/s)

Pressure 0.1 - 9.0 bar (1.45 - 130 psi) 0.1 - 9.0 bar (1.45 - 130 psi) 0.1 - 9.0 bar (1.45 - 130 psi)

Build Volume (XYZ) 150 x 150 x 140 mm (5.91” x 5.91” x 5.51”) 150 x 150 x 140 mm (5.91” x 5.91” x 5.51”) 150 x 150 x 140 mm (5.91” x 5.91” x 5.51”)

Needle Position Control Photo Sensor Photo Sensor Z-Sensor + High Resolution Camera

Camera Resolution (XY) - - 0.009 mm (0.00035”) per Pixel

Needle Sensor Resolution 0.03 mm (0.0012”) 0.03 mm (0.0012”) 0.001 mm (0.00004”)

Minimum Strand Diameter 0.100 mm (0.004”) - Material Dependent 0.100 mm (0.004”) - Material Dependent 0.100 mm (0.004”) - Material Dependent

Number of Materials per Scaffold Maximum 2 Materials Maximum 3 Materials using 3 Print Heads Maximum 5 Materials Using 5 Print Heads

Print Heads Included 2x Fixed High Temperature Heads (includes

adapter for smaller cartriges)

1x Low and 1x High Temperature Head 1x Low and 1x High Temperature Head

Filters Included Particle Filter Particle and Sterile Filters Particle and Sterile Filters

Platform Temperature Control No Heating and Cooling Capable (Chiller not

included)

Heating and Cooling Capable (-10°C to 80°C)

Platform Height Control Manual Automatic Z-height Controlling System Automatic Z-height Controlling System

Material Calibration Manual Material Calibration Manual Material Calibration Semi-Automatic Material Calibration

Additional Features Automated Nozzle Cleaning Process

Built-in PC

Automated Nozzle Cleaning Proces Automated Nozzle Cleaning Process

4 External Temperature Sensor Ports

Layer by Layer Photographic Log

3D Printers 3D Scanners 3D Printing

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Contact Info:

Bruce ReimerStrategic 3D Solutions, Inc.4805 Green Road, Suite 114Raleigh, NC 27616Phone: (919) 324-3912Mobile: (919) 451-5963buce.reimer@strategic3dsolutions.com