Howard A. Kuhn - Additive Manufacturing in the Biomedical Space

Additive Manufacturing Of Bioresorbable Scaffolds

R3D@TRI-C September 9, 2016

Howard A. Kuhn PhD FASM Adjunct Professor, University of Pittsburgh

Technical Advisor, America Makes

Selective transformation of material

having primitive form

(liquid, powder, wire, sheet)

Additive Manufacturing

Additive

Manufacturing

Machine

solid 3D form prescribed

by a CAD solid model into a

0

CAD solid model

Major Applications of Additive Manufacturing

Aerospace

Tooling

Biomedical

Biomedical Applications

Surgery Planning Models

Splints

Exoskeleton Components

Prostheses

Limbs Hearing Aids Dental Aligners

Implants (Replacement Therapy)

Bioresorbable implants (Regenerative Therapy)

Functional Tissue Generation (Organ Replacement)

Taking advantage of additive manufacturing/3DPrinting capabilities for production of patient specific parts:

Windpipe Splint produced by Selective Laser Sintering

of a Bioresorbable Polymer Polycaprolactone

Splints degrade after they’ve

done their job

How about bioresorbable materials for bone repair?

Windpipe Splint produced by Selective Laser Sintering

of a Bioresorbable Polymer Polycaprolactone

Splints degrade after they’ve

done their job

Bioresorbable Materials for Bone Tissue Repair

• Bioresorbable polymer and ceramic alternatives to permanent metal implants or bone grafts

• Advantages – No side effect from long term use

– No secondary surgery

– Potential for multi-functional treatments

• Limitations – Low mechanical properties [1]

– Acidic degradation products (polymers) [1]

– Slow degradation (biocomposites, ceramics, and some polymers) [1,2]

1. J.C. Middleton, A.J. Tipton / Biomaterials 21 (2000) 2335}2346 2. Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 22, No 9 (September), 2006: pp 993-999

Bioresorbable Materials for Bone Tissue Repair

• Bioresorbable polymer and ceramic alternatives to permanent metal implants or bone grafts

• Advantages – No side effect from long term use

– No secondary surgery

– Potential for multi-functional treatments

• Limitations – Low mechanical properties [1]

– Acidic degradation products (polymers) [1]

– Slow degradation (biocomposites, ceramics, and some polymers) [1,2]

How about Bioresorbable Metals ?

Bioresorbable Magnesium alloys

Properties Natural

Bone

Magnesium

alloys

Titanium

alloys

Stainless steel PLGA/PLLA

Density (g/cm3) 1.8–2.1 1.74–2.0 4.4–4.5 7.9–8.1 ~1.3

Elastic modulus (GPa) 14 - 17 41–45 110–117 189–205 7-0.2

Comp, yield strength (MPa) 130–180 250-1000 758–1117 170–310 NA

Tensile yield strength (MPa) 104-120 100-300 700-900 221-1213 27-1

But, pure Mg resorbs too quickly

Through Density Functional Modeling, alloy additions to extend resorption of pure Mg were developed and patented

Properties of Mg alloys closer to those of bone than other implant materials

Bioresorbable Mg Alloy Examples

Bone plates and screws

ACL screw

AV fistula stent 1mm

1mm

Nerve guide

Craniofacial (TMJ) screw

Tracheal stent

Mg Ti

Mg degradation does not inhibit fracture healing

In vivo Tests

Mg enhances bone growth

ERC-RMB Devices Implanted in Animal Models

Orthopedic plates and screws

AV fistula Stents Trachea stent

Kirschner wire Just after

implantation

14 weeks after

implantation

ERC-RMB Devices Implanted in Animal Models

What about Additive Manufacturing

of Bioresorbable Metals?

Conforming bone plates could be produced by additive manufacturing

with properties matched to localized stresses

Image acquisition of bone defect site

Image post-processing and analysis

3D CAD model of bone graft generated

Implant 3D printed from biodegradable metal

Customized biodegradable bone graft substitute by 3DPrinting

Sterilized bone graft substitute is implanted into defect site

Image credit: Synthes CMF Patient Specific Implants

Benefits: • Avoids need for bone grafting • Matching complex 3D anatomical defects reduces

operating room time ($56 per minute) • Eliminates secondary surgery ($58,000 per

operation)

: Biodegradable Metallic Bone Scaffolds

Binder-jet 3D printed prototype scaffolds using pure Mg powder (particle size < 50 μm)

But sintering the scaffolds proved to be difficult

Additive Manufacturing of Mg

BJ 3DP

• Pros: Easily printed

• Cons: Difficult to sinter

SLM/EBM

• Pros: No sintering

• Cons: Low vapor pressure, melting point

Further research is necessary to achieve 3D printing of stable Mg-based alloys

Bioresorbable Fe-Mn alloys

Material Yield

strength

(MPa)

Ultimate

strength

(MPa)

Elongation

(%)

Young’s

modulus

(GPa)

Fe-30Mn

3DP

106 ± 8 115 ± 1 0.73 ± 0.15 32 ± 5

Natural

bone

104-121 86-151 1-3 14-17

Bioresorbable Fe-Mn alloys

Material Yield

strength

(MPa)

Ultimate

strength

(MPa)

Elongation

(%)

Young’s

modulus

(GPa)

Fe-30Mn

3DP

106 ± 8 115 ± 1 0.73 ± 0.15 32 ± 5

Natural

bone

104-121 86-151 1-3 14-17

But Fe-Mn alloys take too long to resorb

ThermoCalc determination of suitable alloying elements to accelerate resorption of Fe-Mn

Material Corrosion potential, Ecorr

[V)

Corrosion current density, icorr

[µA cm-2]

Fe-Mn -0.72±0.04 1.00±0.06

Fe-Mn-1Ca -0.71±0.02 2.12±0.92

Fe-Mn-2Ca -0.66±0.02 6.36±1.75

Fe-Mn-1Mg -0.65±0.02 5.89±0.80

Fe-Mn-2Mg -0.64±0.03 9.16±1.25

~10-fold increase in corrosion rate of 3DP Fe-Mn compared to pure iron

(0.73 to 0.065 mmpy)

Cytotoxicity testing of 3DP Fe-Mn alloys

• Live/dead cell viability assay of the cytotoxicity of 3DP Fe-based alloys

• Pure Fe exhibited no live cells on the surface

• Fe-Mn-1Ca exhibited most live cells (green)

Fe-Mn

3DPrinting of Fe-Mn alloys

Fe-Mn-1Ca

3D printing

& Sintering

20µm 20µm

• ExOne’s RX1 BJ printer was used for this study

• Sintered at 1200 ºC, 3 hours

20µm 20µm

Fe-30Mn 3DPrinted/Sintered parts

Bone cells seeded onto scaffolds

In Vitro results

prototype scaffolds with 1 mm and 500 µm square pores

miniature femur before and after tumble finishing

•High cell attachment

•Cells infiltrated into pores

Chou et al., Acta Biomater. 2013

In-vitro testing of 3DPrinted Fe-30Mn alloys

Technical feasibility

Goat mandible model

2. CT Scan

Goat mandible CT Scan STL file 3DP mandible

BJ/Sintering SLM - Renishaw

Next Steps

In-Vivo Testing

Innovative Design (for 3DPrinting)

of Bone Implants

To Your Good Health

Acknowledgements: Drs. Daeho Hong, Da-Tren Chou, Abhijit Roy, Prashant Kumta