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Presentation | Nov 2013 MT-5009 Analyzing Hi-Tech Opportunities 3D Printing - Biological Applications By Anand (A0068259) Archit (A0098517) Arun (A0081990) Hemant (A0068251) Yuwei (A0118280)
46

3D Bio-Printing; Becoming Economically Feasible

Sep 14, 2014

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These slides use concepts from my (Jeff Funk) course entitled analyzing hi-tech opportunities to analyze the increasing economic feasibility of bio-printing. Due to a lack of available kidney and other organ donors for organ transplants, 3D printing has emerged as an important alternative for many people. Bioprinting is done by using a computer model of an individual’s body to generate a data set for an organ that can be printed with a 3D printer and grown in a bio-reactor. The falling cost of materials and 3D printers is improving their economic feasibility.
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Page 1: 3D Bio-Printing; Becoming Economically Feasible

Presentation | Nov 2013

MT-5009 – Analyzing Hi-Tech Opportunities

3D Printing - Biological Applications

By Anand (A0068259) Archit (A0098517) Arun (A0081990)

Hemant (A0068251) Yuwei (A0118280)

Page 2: 3D Bio-Printing; Becoming Economically Feasible

Introducing 3D printing

Presentation | Nov 2013

• What is it

– Generation of a 3D solid model virtually of any orientation from a digital medium.

– Additive printing technique - Improvised form of rapid proto-typing.

• Why was is it

– Fascination with the idea of replication.

– Deserted scenario :The need for replication technology.

• When was it

– Based on the first Patent published in 1984 under Stereolithography.

– Stereolithography: Using UV beam to solidify photopolymers.

• Where was it commercialised

– 3D systems: First commercial rapid prototyping technology.

Page 3: 3D Bio-Printing; Becoming Economically Feasible

• Additive – Generating 3D object through sequential layering of material.

Extrusion

Fused-deposition modeling (FDM)

Wire

Electron-Beam Freeform Fabrication(EBF3)

Granular

Direct metal laser sintering (DMLS)

Electron-beam melting (EBM)

Selective laser melting (SLM)

Selective heat sintering (SHS)

Selective laser sintering (SLS)

Powder-bed and inkjet-head 3D

printing

Plaster-based 3D printing (PP)

Further development in Inkjet printing

Laminated

Laminated-object manufacturing (LOM)

Light polymerised

Stereolithography (SLA)

Digital-Light Processing (DLP)

Further development in Inkjet printing

Evolution of 3D printing

Presentation | Nov 2013

Page 4: 3D Bio-Printing; Becoming Economically Feasible

Inkjet Printing

Inkjet

printing

(1956)

Printing Materials

Conventional printing paper

Non conventional printing Other than paper

Functional material E.g. Conductive Ink

Printing Technology

Drop – on – demand

Thermal

Piezoelectric

Squeeze tube

Bending

Pushing

Shear mode

Electrostatic

Acoustic

Continuous printing

Binary Deflection

Multiple deflection

Hertz

Microdot Ink jet material deposition

Organic light emitting diodes

Printed Circuit boards

– Conductive Ink

Presentation | Nov 2013

Page 5: 3D Bio-Printing; Becoming Economically Feasible

Performance Metrics

Stereolithography (SLA) Fused Deposition Modeling (FDM) Selective Laser Sintering (SLS) Multi-Jet Modeling (MJM – 3DP)

The Future of 3D Printing; http://replicatorworld.com/issue-printer/overview-2012

Generation of metric for biomedical application "bioprinting fidelity index" (BFI)

Attributes to performance • Affordability, • Material Availability • Precision

• Geometric scaling • Strength • Time

Presentation | Nov 2013

Page 6: 3D Bio-Printing; Becoming Economically Feasible

Over hyped technology

3-D printing to be next $1-trillion industry

In reality , the time for Investment in disruptive technology should be right after the spike in patent filing signaling a new wave of product /service/application and not after a hype-spike

10 Reasons to Be Wary of 3-D Printing Stocks (Part 1)

http://www.techandinnovationdaily.com/2013/02/01/3-d-printing-warning-part-1/

Impact of 3D printing

Presentation | Nov 2013

Page 7: 3D Bio-Printing; Becoming Economically Feasible

Presentation | Nov 2013

Applications of 3D printing

Manufacturing

3D Printing

Processes Applications Industries Demographics

Category

Class

Material

Modeling

Manufacturing

Tooling

Prototyping

Healthcare

Entertainment

Art

Engineer

Consumer

Practitioner

Artist

Page 8: 3D Bio-Printing; Becoming Economically Feasible

Jewellery Tooling

Presentation | Nov 2013

Applications of 3D printing

Page 9: 3D Bio-Printing; Becoming Economically Feasible

Fashion Architecture

Applications of 3D printing

Presentation | Nov 2013

Page 10: 3D Bio-Printing; Becoming Economically Feasible

Organs Medical Applications

Presentation | Nov 2013

Applications of 3D printing

(Our Focus: Bioprinting)

Page 11: 3D Bio-Printing; Becoming Economically Feasible

3D-Bioprinting Technology

Presentation | Nov 2013

Page 12: 3D Bio-Printing; Becoming Economically Feasible

The Singapore predicament

Number of organs donated for transplants in Singapore remains dismally low, despite a law requiring donations by all after death. Source: healthxchange.com.sg

“ ”

Presentation | Nov 2013

Page 13: 3D Bio-Printing; Becoming Economically Feasible

The coveted “Organs”

• 117,521 people in US in need of organ.

• Hostilities in Singapore despite HOTA.

• Kidneys, hearts, livers, lungs are most coveted.

• Organs not usable despite donation.

Source: The Boston Globe Presentation | Nov 2013

Page 14: 3D Bio-Printing; Becoming Economically Feasible

Fiction meets reality

Bio-printing is an automated computer aided layer-by-layer deposition of biological materials for manufacturing of functional human organs.

Source: Organovo.

Artificial bioprinters have already been built.

NovoGen MMX® built by Organovo and Invenech.

Presentation | Nov 2013

Page 15: 3D Bio-Printing; Becoming Economically Feasible

Bioprinting deconstructed

• Intrinsic nature of cells to coalesce1, tissues to self-assemble2 and fluidity of embryonic tissues3.

• Organ printing mimics the natural biological process of embryonic cellular fusion.

Source: 1Mironov et al., Anat. Rec., 2Wilson, H.V., J. Exp. Zool., 3G. et al. Biophys. J.

Presentation | Nov 2013

Page 16: 3D Bio-Printing; Becoming Economically Feasible

Bioprinting process flow

Source: 1nlpnow.com., 2tissueinformatics.com, 3med.umich.edu.

Computer model

Printing Post-

processing

Computer

tomography1

Vasculature2

Most challenging

Layer-by-layer

Config.3

Presentation | Nov 2013

Page 17: 3D Bio-Printing; Becoming Economically Feasible

Computer model

Printing Post-

processing

Bioprinting process flow

Source: organovo.com.

3 important components: Bioink, Biopaper, Bioprinter.

Bioink (cells of sp. organ), Biopaper (collagens, nutrients)

Presentation | Nov 2013

Page 18: 3D Bio-Printing; Becoming Economically Feasible

Computer model

Printing Post-

processing

Bioprinting process flow

Bioreactor

Supply nutrients for further cell growth

Physiological environment

for tissue maturation.

Mechanical and bio. testing.

Presentation | Nov 2013

Page 19: 3D Bio-Printing; Becoming Economically Feasible

Bioprinting Roadmap

Presentation | Nov 2013 Source: organovo.com.

Page 20: 3D Bio-Printing; Becoming Economically Feasible

Current Progress

Ear1: 250 mn cells and collagen from rat tail make human ear in 15 min. Post-processing 3 months. To serve children with hearing loss due to malformed outer ear.

Kidneys2: Layer-by-layer building of scaffold and deposition of kidney cells. Assembly to be transplanted into patient. Degradation of scaffold to follow in-vivo.

Source: 1Cornell University., 2Wake Forest Inst., 3Univ. Of Pennsylvania.

Blood Vessels3: Rigid but non-toxic sugar filaments form core. Cells deposited around filaments. Subsequent blood flow dissolves sugar.

Presentation | Nov 2013

Page 21: 3D Bio-Printing; Becoming Economically Feasible

Current Progress Skin grafts1: laser scan wound to determine depth and area. One inkjet ejects enzymes and second, cells. Layer is finally sealed by human skin cells. Useful in war and disaster zones.

Bones2: Print scaffold with ceramic or Titanium powder. After 1 day in culture of human stem cells, its ready. Repair of complex fractures in accident survivors.

Source: 1Wake Forest Inst., 2 Washington State University, 3Organovo

Drug testing3: $1.2bn to make a new drug in 12 years.

1 in 5000 has a chance to make it to market.

20-50% drug fail from pre-clinical animal trails to human trials.

Presentation | Nov 2013

Page 22: 3D Bio-Printing; Becoming Economically Feasible

Presentation | Nov 2013

Market Research & Entrepreneurial

Opportunities

Page 23: 3D Bio-Printing; Becoming Economically Feasible

Presentation | Nov 2013

Biomaterial (Bio-ink, Bio-paper) Market

Million USD

Source: US market for Biomaterials

Page 24: 3D Bio-Printing; Becoming Economically Feasible

Presentation | Nov 2013

(a) (b)

Figure: Graphs showing the price reduction of Biomaterials; (a) Collagen; (b) Polycaprolactone;

Biomaterial Cost projections

Year Cost of cells (500 ml) SGD

2011 225

2012 217

2013 216

Table: Cost of cells from 2011 to 2013

Source: Sigma-Aldrich

Page 25: 3D Bio-Printing; Becoming Economically Feasible

Presentation | Nov 2013

Biomaterials:

Reason for cost reduction

• Increase in the number of manufacturers.

• Mass production.

• Increase in demand.

• Invention of new materials with lesser cost.

• Local manufacturing and reduced inventory.

• Novel material compositions and properties.

• Multifunctional materials.

Page 26: 3D Bio-Printing; Becoming Economically Feasible

Presentation | Nov 2013

Bioprinters: Cost

Minimum Price: $15,000

Minimum Price: $ 500

2008

2013

Source: http://disruptiveinnovation.se/?p=286

Page 27: 3D Bio-Printing; Becoming Economically Feasible

Presentation | Nov 2013

Bioprinters: Cost

Reason for cost reduction

• Well established technology.

• Lesser IP’s

• Increase in the number of market players.

• Economies of scale.

• Increase in demand.

• Local manufacturing and reduced inventory.

• Cheaper and more accessible after market parts and repair.

• Multifunctional structures.

We believe that the cost of Bioprinters will reduce further in future.

Page 28: 3D Bio-Printing; Becoming Economically Feasible

Presentation | Nov 2013

Bioprinters: Performance

1. Accuracy

Source: Biomaterials as biopaper by Rana Imani

Page 29: 3D Bio-Printing; Becoming Economically Feasible

Presentation | Nov 2013

Bioprinters: Performance

2. Time

Source: http://inhabitat.com/3d-printed-bones-are-saving-a-uk-hospital-thousands-in-fees/3d-bone-imaging-printing-4/

• Increasing the number of liquid dispensing nozzle is one way to speed up the process to reduce the time.

Page 30: 3D Bio-Printing; Becoming Economically Feasible

Presentation | Nov 2013

Comparative Analysis and Projections

Source: 3D Printing: An Interview with Anthony Vicari

Page 31: 3D Bio-Printing; Becoming Economically Feasible

Presentation | Nov 2013

Competitors Influence

Source: Organovo.com; *Cytograft public materials

Page 32: 3D Bio-Printing; Becoming Economically Feasible

Presentation | Nov 2013

Today’s Scenario

• 115,000 people currently need organ transplants in the US.

• 10 people die every day while waiting for their transplant.

Source: www.ivhn.org

Year

Dem

an

d f

or

Org

an

s

Page 33: 3D Bio-Printing; Becoming Economically Feasible

Presentation | Nov 2013

Cost Analysis

Rough estimates on the total cost of Organ Transplants

Source: U.S Organ and tissue transplant cost estimates and discussion

Estimated U.S. Average 2011 Billed Charges Per Transplant

Page 34: 3D Bio-Printing; Becoming Economically Feasible

Presentation | Nov 2013

Cost Analysis

Case Study on Bioprinting of Kidney

Source: Fung Technical Report No. 2013.04.17; * www.ted.com

• Dialysis treatment costs $55,000-$75,000 per patient per year.

• Treatments for diabetes costs around $6,000 per year per patient.

• Total cost of $245 billion per year has been spent in the United

States for diabetes treatment.

• Cost of Kidney Transplant : $ 80,000 USD • Cost for Bioprinting of Kidney : $ 280,000 USD*

* Projected cost for bioprinted kidney 2013

Takes around 10 hours to bioprint a Kidney*

Page 35: 3D Bio-Printing; Becoming Economically Feasible

Presentation | Nov 2013

Cost Analysis - Pricing Projections

S. No Year Demand for Kidney Price (USD)

1 2014 113,000 247,500

2 2016 126,500 221,000

3 2018 140,700 199,000

4 2020 156,000 180,000

5 2022 172,600 162,000

6 2024 190,300 147,000

7 2026 209,200 134,000

8 2028 229,200 122,000

9 2030 250,000 112,000

Table: Pricing Projections on Bioprinting of Kidney in United States*

* Projections are purely based on the demand for kidney in United States.

Cost of Bioprinted Kidney < 120 K USD by 2030

Assumption: To estimate the pricing projections, the revenue of the company is maintained constant.

Reasons for Cost Reduction: • Continuous increase in demand. • Increase in the number of Competitors. • Continuous decrease in the cost of biomaterials. • Continuous decrease in the price of bioprinters. • Economies of scale. • Local manufacturing and reduced inventory. • Cheaper and more accessible after market parts and repair.

Page 36: 3D Bio-Printing; Becoming Economically Feasible

Presentation | Nov 2013

Entrepreneurial Opportunities

• Making of design model, the printer and the bio-material.

• Dentists can utilize patients’ unique teeth layout and bone scans to create friendlier implants and

prosthetics.

• Manufacturing of multipurpose 3D printing heads and nozzles.

• Synthetic materials for manufacturing tissues, bones, cartilage and organs.

• “Organ lockers,” a system that provides secure storage and transportation for customer’s organs.

• Scanning Kiosks.

• Manufacturing and distribution of Bio-inks and other biocompatible materials for 3D bio printing.

• Packaging of the 3D bioprinted organs.

Page 37: 3D Bio-Printing; Becoming Economically Feasible

Presentation | Nov 2013

Entrepreneurial Opportunities

Commercial Areas

Blood Vessels

Cartilage Grafts

Cardiac Muscle Grafts

Nerve Re-growth

Page 38: 3D Bio-Printing; Becoming Economically Feasible

Presentation | Nov 2013

Industrial Impacts

Positively Impacted Industries Negatively Impacted Industries

Patients who are cured by 3D bioprinting technology are the big winners.

• Bio-ink, scaffolds and Biocompatible

materials manufacturers.

• 3D Bioprinters manufacturers.

• Hospitals & insurance companies (no

longer need to spend money on transplant

logistics).

• Stem-cell harvesting and storage business.

• Surgical supplies companies.

• Computer aided design (CAD) software

companies.

• Kidney dialysis industries.

• Companies that supply blood sugar testing

supplies.

• Companies that produces and supplies

insulin, pills and insulin pumps.

• Companies that sell pacemakers, new

heart valves.

• Organ replacement logistics.

Page 39: 3D Bio-Printing; Becoming Economically Feasible

Presentation | Nov 2013

SWOT Analysis

Strengths

• All vital organs can be printed by one 3D bioprinter.

• Easy to build own custom machine.

• Easy to make body parts with desired size and shape.

• Huge market potential.

• Provides several entrepreneurial opportunities.

Opportunities

Improving machine possibilities

• larger models.

• faster printing.

• multi colour prints.

• active development of biocompatible materials.

• customization of designs based on customer needs.

Threats

• Technology background of the user.

• Time taken for printing an organ.

• Cost of organ printing.

• In wrong hands, may contribute to fake identity, increase in crime and illegal activities.

Weaknesses

• Quality of the organs printed.

• Production time.

• Technolgy is still in prematured state.

• Expensive.

S W

T O

Page 40: 3D Bio-Printing; Becoming Economically Feasible

Presentation | Nov 2013

Bioprinting - Forecast

• Printing medication

• Printing new Skin

• Printing cartilage & bones

• Printing replacement

tissues

• Printing replacement

organs

• Printing stem cells

• Specific organ tissue replacement for important organs such as heart and kidney. • Personalized replacement 3D printed joints (hip, knee) with custom fit. • Life saving 3D printed organ replacement (high cost.

• Replacement 3D printed organs commonly available at affordable cost. • Liver Kidney replacement companies achieve maturity. • 3D printed tissue replacement for all body organs available. • Printing medication at home widely available.

Research (today)

Technology Adoption (3 - 5 Years)

Commercialization (5 - 7 Years)

Page 41: 3D Bio-Printing; Becoming Economically Feasible

Pro’s and Con’s Analysis

• Takes less time than lab-grown artificial organs, therefore,

future demand looks bright.

• However, organ printing has certain disadvantages and

limitations compared to lab-grown organs.

• Lab-grown organs get to take the time for the different cell

types to start integrating and function with each other while

organ printing does not give quite the same opportunity.

• In 10 years, the number of patients that require organs will

have doubled.

• Is a bio-fabrication line possible?

• Many challenges ahead and aspects left to improve before

commercialization of organ printing.

Presentation | Nov 2013

Page 42: 3D Bio-Printing; Becoming Economically Feasible

Pro’s and Con’s Analysis

• Vascularization, scaling, the interaction between the

different cell types, well-functioning organs that can be

integrated into the patient’s body.

• From a systems engineering point of view, it will require

more than bio-printers to produce complex tissues and

organs.

• Bioprinters alone will not be enough for producing the

artificial organs. Steps such as fusion, assembling,

remodeling, maturing are required.

• Quality control a crucial matter!!!

Presentation | Nov 2013

Page 43: 3D Bio-Printing; Becoming Economically Feasible

Thank You

Presentation | Nov 2013

Page 44: 3D Bio-Printing; Becoming Economically Feasible

Presentation | Nov 2013

Supporting Info: Bio-inks

• Prepared by mixing cells with biocompatible materials (Hydrogels).

• Suitable hydrogels are chosen based on the Organ to be printed.

(Ex. Collagen is widely used for bone printing)

Source: C. J. Ferris et al. Biomaterials Science 2013, 1, 224-230.

• Collagen • Alginate • Fibrin • Polycaprolactone • Thorbin

Bio-ink materials

Collagen Fibrin

Alginate

• Excellent Biocompatibility. • Homogenously incorporate cells, growth factors. • Processed under mild conditions. • Easy chemical modification. • Sol-gel transition.

Widely used

reason

Page 45: 3D Bio-Printing; Becoming Economically Feasible

Presentation | Nov 2013

Supporting Info: Bio-papers

Supports the Bio-ink during processing steps and post processing steps.

Source: Nakamura et al. Biofabrication 2 (2010) 014110

Page 46: 3D Bio-Printing; Becoming Economically Feasible

Presentation | Nov 2013

Supporting Information