3D printing biomaterials

CAM

software to manufacture 3D objects

CAD

software to create 2D or 3D designs

additive process

layer by layer deposition of material to fabricate a 3D object

can be used for metals and ceramics

How is 3D printing used in medicine?

Various products can be 3D bio printed as a results of a CT or MRI scan. It can have a high structural complexity and quick fabrication at a low cost. For example, you can get a medical imaging scan of an ear and then 3D print that image.

What are the 3 main problems with conventional scaffold fabrication?

1. Can’t control the size, shape, distribution, or inter connectivity

2. Organic solvents such as chloroform are used to dissolve the synthetic polymers

3. After scaffold fabrication, the presence of organic solvent residues can be toxic to cells

What is the SFF manufacturing technique?

• produce complex 3D structures by selectively adding material

• 2D layers are stacked layer by layer on a platform

• allows for controlling the scaffold parameters such as size, shape, distribution, and inter connectivity of pores

What are some examples of 3D prints in medicine?

• craniofacial implants

• dental molds, crowns, and implants

• prosthetics

• rapid prototyped medical equipment

• surgical models

• scaffold for skin and bone tissue regeneration

• organic printing

• tissue models for drug discovery

What are the 2 major issues with 3D printing in medicine?

1. slow printing speed and low resolution

2. lack of diversity in 3D printable biomaterials

Need for organs: How many people in the US in need of organ? How many organ transplants each day? How many die from lack of one?

116,000

79

20

What are the most needed organs? (4)

Kidneys, hearts, livers, lungs

What are some factors taken into account when choosing a biomaterial ink?

1. printable

2. biocompatible

3. mechanical properties

4. degradation kinetics

5. degradation byproducts

6. tissue biomimicry

What are the 5 biomaterial inks?

Ceramic, polymer, hydrogel, composite, cells/ECM components

Explain extrusion-based methods for 3D printing.

• ink goes through a nozzle as a viscous liquid or melt

• forms individual lines that solidify on a build plate

• as material is extruded, the nozzle follows predefined path determined by a computer model

• builds up a 3D object layer-by-layer

FDM (fused deposition modeling)

• extrusion based method

• ink is a solid filament (1.5-1.75 mm diameter) that is heated up in the nozzle to be melted and flowable

• extruded it’s a motorized pinch roller system

• resolution is about 200-400 micrometers (25 in x and y plane)

• requires polymer filaments that have sharp solid to melt transition

  • elastic modulus to melt viscosity ratio below 5×105 s-1 to prevent buckling and shear thinning

  • irreversible structural changes due to flow-induced deformations

  • thermoplastic or thermoset

DIW or robocasting (direct ink writing)

• extrusion based method

• inks solidify through evaporation, gelatin or other temperature or solvent induced phase change

  • inks are polymer dissolved in rapidly evaporating organic solvent that results in a solid polymer

  • inks need to dry in seconds to minutes to maintain shape

  • 20-30 wt% support polymer solubility

  • low viscosity to facilitate printing and shear thinning to flow and prevent clogging in the nozzle

• hydrogels structural integrity improved postextrusion due to using shear-thinning fluids or temperature sensitive or cross linking

• resolution 100 micrometers to mm (25 micrometers in x y plane)

Why do fillers materials need to be added to FDM and DIW?

their filaments lack the material strength to support themselves upon extrusion which leads to sagging. should add filler materials that can be removed postprinting via burning out or dissolving

what are particle fusion-based methods primarily used for?

hard-tissue engineering applications such as orthopedics and oral surgeries

selective laser sintering (SLS)

• particle fusion based methods

• directed laser beam to hear I polymers, ceramics or metallic powders

• causes particles to fuse together along the outermost surface

• laser scans the shape of a cross-section onto the surface of a powder bed

• then a new layer of powder is deposited by a roller

• ink is a fine powder (1-10 microns)

  • polymer beads up to allow for particle flow within the bed while maintaining pint resolution

  • melt temperature below 200C used and low melt viscosity

• resolution is 50-300 microns

• surface functionalization (modifying the outermost layer of a material to alter its properties) to eliminate electrostatic forces

• slow, expensive, requires tons of material

• used for hard tissue engineering

selective laser melting & direct metal laser sintering (SLM & DMLS)

• particle fusion based method

• use laser to scan and selectively fuse or melt metal powder particles, bonding the together and building layer-by-layer

• material used is metal that comes in granular form

  • metal powder is highly recyclable, less than 5% is wasted

• metal printed parts have higher strength and hardness, often more flexible, but more prone to fatigue

Particle binding (PB)

• particle fusion based method

• liquid binding solution to fuse particles together within each layer

• followed by high temp, sintering step to solidify the final 3D object postproduction

• used for hard-tissue engineering

stereolithography (SLA)

• light assisted-based method

• original additive manufacturing method

• patterning beam of light over a bath of photopolymerizable liquid monomer or polymer to create a single hardened polymer layer

• after polymerization, the building stage lowers into the solution to allow for a new resin to flow over the printed surface

• next layer is polymerized on top of the previous layer

• lower resolution than 2PP (constructs in cm and resolution 80-126 microns vraj 10 nm resolution)

• inks:

  • photo-crosslinkable polymers that react and polymerize rapidly under UV radiation

  • liquid bath needs to be viscous enough to hold its shape but also thin enough to flow back into place quickly, and able to harden fast so the print stays sharp and quick

limitations of light assisted based methods

• harsh nature of UV based cross linking

• extensive post process

• trapping of liquid resin

• trapped liquid resin within the end

• lack of available biocompatible and biodegradable materials

laser induced forward transfer (LIFT)

• light assisted based method

• transparent support layer

• then layer absorption layer

• then layer with deposition layer

• absorbs the laser light, leading to evaporation of the coating

• the evaporation leads to a high-pressure bubble expanding toward the 20-40 micron hydrogel layer to cushion the impact

• finally goes to the material deposition (applying the layers)

Inkjet printing

• computer printing that recreates a digital image by propelling ink droplets onto paper, plastic, etc.

• small volumes of droplets form nozzle to printing surface (1-100 picoliters)

• forms structures after solidifying

• multinozzle inkjet print heads contain several hundred individual nozzles to accelerate printing process

• classified based on droplet generation:

  • continuous inkjet (creates a jet)

  • drop on demand (higher resolution)

continuous inkjet (CIJ)

• inkjet printing

• coding and marking products and packages

• pumps fluid directly from a reservoir to one or more small nozzles

• continuous stream of drops (100 microns) at high frequency using vibrating piezoelectric crystal (50K-175K Hz)

• drops pass through electrodes that give charge onto each drop

• charged drops pass a deflection plate that has an electrostatic field to select which drops will be used for the print and which ones will be collected for reuse

drop on demand (DOD)

• inkjet printing

• individual drops (25-50 microns generated when needed

• drops are formed by pressure pulse within the print head (thermal and piezo)

  • THERMAL: rapidly heating resistive element in small chamber containing the ink (350-400 C)

  • THERMAL: causes thin film of ink above heater to vaporize into a rapidly expanding bubble, causing pressure pulse that forces an ink droplet through the nozzle

  • PIEZOELECTRIC: piezoelectric crystal undergoes distortion when an electric field is applied

  • PIEZOELECTRIC: distortion is used to create a pressure pulse in the ink chamber, causing the drop to be ejected

• commonly used for tissue engineering

• good spatial resolution with positional accuracy (about 10 microns in x-y axis)

• used in consumer desktop printers

Drop on demand (DOP) is piezoelectric or thermal used more often? what are advantages and disadvantages of the preferred method

• heating can be done in microseconds but most researchers use piezoelectric

• there is a variety of fluids and long life of printheads for piezoelectric

• however, high cost

inkjet printing considerations

• biological materials like cells can be incorporated into the ink to create bio inks

• need to think about shear forces and temperature change at the point of extrusion

• cell density needs to be limited to maintain droplet formation and reduce clogging and shear stress

• applications: bioadhesives, scaffolds, living cells, and pharmaceutical applications

3 commonly used polymeric biomaterial inks and why

polypropylene, chitosan, poly lactic acid

• ease of processability

• low cost

• biocompatible

• degrades well

• mechanics

poly lactic acid (PLA) ink

• polymeric biomaterial inks shear forces

• best for FDM printing

• low cost

• nontoxic

• biocompatible

• easily processable

• no heating plate needed

• no smell

• extrudes between 200-230 C

• transparent

• brittle and low compressive strength

• composites with ceramic for bone applications

• tm ~175

PCL inks

• polymer biomaterial ink

• low cost

• biodegradable

• good mechanical properties

• stable in the body for 6 months then degrades in 3 years

• quicker to get to market cuz lax regulations

• can make scaffolds or airways splint for emergency use as examples

• Tm ~60 LOW

PEEK ink

• semicrystalline to create craniofacial implants

• HIGH Tm 350 when mixed with SLS

• inert

• biocompatible

• radiolucency (can see stuff thru it on x-ray)

• low heat conductivity

• strength and elasticity similar to cortical bone

• not osteointegrative (can’t directly connect to living bone)

• heat resistant, can sterilize with steam without softening it

advantages of 3D printing prosthesis

• cheap

• can easily personalize

• can incorporate various things like pressure sensors, myoelectric control (send signals from muscles to operate prosthesis), actuators, complex movements

• free platforms to download stuff

• rigorous FDA testing

3D printing SLA prosthesis advantage and disadvantage

• high resolution so can design with very fine details things like joints or complex structure that easily mimic natural body functions

• but high cost of equipment and resin

challenges with 3D printing prosthesis

• durability with daily use

• integrating electric components

• sensitivity with myoelectric components

• lack of clear regulations

precision, speed, cost, and applications for four types of prosthesis 3D printing technology

PRECISION (high to low)

1. metal 3D printing

2. SLS

3. SLA

4. FDM

PRINT SPEED (high to low)

1. FDM

2. SLS

3. SLA

4. metal 3D printing

COST (high to low)

1. metal

2. SLS

3. SLA

4. FDM

applications:

1. FDM: low-cost prototypes and economical prosthesis

2. SLA: high detailed prosthesis, especially small parts and aesthetic stuff

3. SLS: robust resistant and customized prosthesis for functional applications

4. metal: bionic or mechanical prosthesis with strong and resistant structures like hip implants and joints

Hydrogel inks (shear, common materials, how they’re stabilized, approaches)

• shear thinning when going through the nozzle

• made from alginate, gelatin, hyaluronic acid, PEG, fibrinogen, agar, hybrids/other synthetics

• stabilized by increasing cross-linking density network in a solution that contains physical or chemical crosslinkers or UV

• direct write bio printing (directly deposit the hydrogels in precise 3D patterns layer-by-layer)

  • use gelatin for hydrogel

  • and a bit of photoinitiator so it will react when exposed to UV

  • put under UV for 10-60 sec, strengthens print

• can use decellularized ECM from adipose, cartilage or heart tissue

  • PCL framework in addition to hydrogel

• can mix gelatin slurry with CaCl2

  • makes bingham plastic (rigid at low stress but flow at high)

  • little bit of alginate too

ceramic based ink

• try to limit this type of ink because high Tm (above the range of FDM and ceramics cannot be used in SLA and SLS hard to get dense and porous structures)

• inkjet and PB can be done with powder and suspension forms

• can be used as additive to composite system as well

• poly acrylic acid or phosphoric acid onto HA powder then sinter

• tailor ink composition and viscosity to make scaffolds from HA with minimal solvent

smart materials in 3D bio printing

• can reshape or transform in response to external stimuli such as self-folding, assembling and dissassembling

• PNIPAA and PCL and PEG for example

cell maturation in 3D bioprinting

• someone’s printed microtissue can undergo maturation form cellular coating, cell self-organization and matrix deposition then gradually form functional tissue

• seen with endothelial cells and spheroids they have formed around a graft

what can we print?

• cells and extra cellular matrices

• NOT organs or tissues at once

servo motor versus stepper motor and bipolar motor

• servo has continuous feedback between controller and motor

• stepper does not need constant feedback, goes by movements

• bipolar activates different poles

piezoelectric extruder

• creates specific current that cuts the flux

• dispenses uniform drops

• complex

micro valve extruder

• flux then force then cuts flux then opens and closes valve

• drops are not uniform, start to decrease in size over time cuz plastic syringe deforms from force

syringe extruder

• best

• switch off motor, dispense fixed amount of liquid, move to new position, repeat

• uniform drops

problems when dispensing drops from extruders (size of drops remain the same but what is happening)

• size of drop remains the same, but number of cells in the drop decreases

• need to make fluid more viscous but also can’t be too high because strong force could kill the cells

• need to also be more packed together in the fluid

what is a mixer extruder

• mixes material as it prints

• alginate and CaCl cross links immediately and blocks exit

• used for materials that slowly cross link

• controlled via stepper motor

what is a pneumatic extruder

• for things that cross link quickly

• has pregel then adds a little CaCl2 and then prints, then adds the rest of it afterwards to finally cross link

• the hydrogel needs to be cross linked

• uses compressor and pressure controller

turbidometry

analysis of how liquid phase becomes solid overtime

• good to know for what the printing window is for pregels

rheology

• mechanical properties of hydrogels/bioink/pregels

• shear thin is ideal because it allows it to be viscous enough to dispense and then maintain shape after

printibility

• ability to obtain a shape after extruded

• able to stack layers without melting on top of each other