G:\Biomaterial Fabrication

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ARJUN G NAMBOODIRI Polymer processing Laboratory 4/6/10 BIOMATERIAL FABRICATION TECHNIQUES

description

fabrication of biomaterials with emphasis on rapid prototyping techniques

Transcript of G:\Biomaterial Fabrication

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ARJUN G NAMBOODIRIPolymer processing Laboratory

4/6/10

BIOMATERIAL FABRICATION TECHNIQUES

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OVERVIEW

INTRODUCTION

USE OF BIOMATERIALS

MATERIALS USED AS BIOMATERIALS

EVOLUTION OF BIOMATERIALS

SCAFFOLD FABRICATION TECHNIQUES

LIMITATIONS

RAPID PROTOTYPING

TOWARDS NANOTECHNOLOGY

CONCLUSION

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INTRODUCTION

“Non viable material used in medical devices

intended to interact with biological systems”

(Williams 1987)

A biomaterial is "any substance (other than drugs) or combination of substances synthetic or natural in origin, which can be used for any period of time, as a whole or as a part of a system which treats, augments, or replaces any tissue, organ, or function of the body".

BIOMATERIAL

ONE MUST HAVE EITHER VAST KNOWLEDGE OR DIFFERENT

COLLABORATORS WITH DIFFERENT SPECIALITIES INORDER TO

DEVELOP BIOMATERIALS IN MEDICINE AND DENTISTRY

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USE OF BIOMATERIALS

REPLACEMENT OF DISEASED OR DAMAGED

PARTS

ASSIST IN HEALING

IMPROVE FUNCTION

CORRECT FUNCTIONAL ABNORMALITIES

AID TO DIAGONISE

AID TO TREATMENT

CORRECT COSMETIC PROBLEMS

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MATERIALS FOR USE AS BIOMATERIALS

1. Polymer: Nylon, Polytetrafluoroethylene,

Polyurethane, Silicone rubber,

polycaprolactone

2. Metals: Ti, Co-Cr alloy, Stainless Steel, Pt, Au

etc

3. Ceramics: Aluminum oxide, Calcium phosphate,

Hydroxyapitite, Carbon etc

4. Composites: Fiber reinforced bone cements etc

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Evolution of Biomaterials

Structural

Functional Tissue Engineering Constructs

(Scaffolds)

Soft Tissue Replacements

First generation

Second Generation

Third Generation

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SCAFFOLD FABRICATION TECHNIQUES

Solvent Casting and Particulate Leaching

Melt molding

Gas Foaming

Fiber bonding

Freeze drying

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SOLVENT CASTING/ PARTICULATE LEACHING

1. Incorporation of Salt particles

2. Polymer/solvent solution e.g. PLLA/chloroform

3. Casting

4. Vacuum dry

5. Immerse in water

• salt particles of a specific diameter to produce a

uniform suspension (Mikos et al., 1994,1996).

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Advantage - Highly porous scaffold with porosity up to

93% and an average pore diameters up to 500

um can be prepared using this technique.

Disadvantage - A disadvantage of this method is that it can

only be used to produce thin wafers or membranes up to

3mm thick.

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MELT MOLDING

This process involves filling a mould with polymer

powder/melt and obtaining the shape of the mould.

MELT MOULDING

COMPRESSION MOULDING

INJECTION MOULDING

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In the work done by Thompson et al in 1995 they used the

COMPRESSION MOULDING PRINCIPLE where a TEFLON

MOULD was used with PLGA and gelatin micro spheres of

specific diameter, and then heating the mould above the

glass-transition temperature of PLGA while applying

pressure to the mixture (This treatment causes the PLGA

particles to bond together.

Once the mould is removed, the gelatin component is

leached out by immersing in water and the scaffold is then

dried.

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GAS FOAMING

Another approach to using gas as porogen was

developed by Nam et al. (Park, 1999; Nam et al.

2000).

This technique includes both melt moulding and

particulate leaching aspects.

Porosities as high as 90% with pore sizes from 200-

500 um are attained using this technique.

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Fabrication process

•Ammonium bicarbonate is added to a solution of

polymer in methylene chloride or chloroform.

•The resultant mixture is highly viscous and can

be shaped with a mold.

•The solvent is then evaporated and the composite

is either vacuum dried or immersed in hot water.

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FREEZE DRYING

The pore size can be controlled by the freezing rate and pH; a fast freezing rate produces smaller pores.

Freeze-drying works by freezing the material and then

reducing the surrounding pressure and adding enough

heat to allow the frozen water in the material to sublime

directly from the solid phase to the gas phase.

Yannas et al., 1980 Collagen scaffolds have been made by freezing a dispersion or solution of collagen and then freeze drying.

Dagalakis et al., 1980; Doillon et al., 1986

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FIBER BONDING

PGA fibers are immersed in PLLA solution.

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LIMITATIONS

1. Poor mechanical integrity

2. Residual organic solvents

3. Lack of structural stability

4. Some techniques can only be used to make very small

membranes.

5. All the materials cannot be used for all the processes.

6. Difficult to control membrane porosity and morphology.

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RAPID PROTOTYPING TECHNIQUE

3D Solid modeling

Data preparation

Part Building

Redesign

Pass

Reject

A family of

fabrication

processes

developed to make

engineering

prototypes in

minimum lead time

based on a CAD

model of the item

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BENEFITS:

1) Reduced lead times to produce prototype components.

2) Improved ability to visualize the part geometry due to its

physical existence.

3) Earlier detection and reduction of design errors.

4) Increased capability to compute manufacturing

properties of components and assemblies.

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RAPID PROTOTYPING PROCESSES

Three Dimensional Printing (3DP)

Stereolithography (SLA)

Selective Laser Sintering (SLS)

Fused Deposition Modeling (FDM)

Organ printing

Membrane lamination

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Technology invented at MIT by Bredt et al (1998)1. Layer of powder spread on platform2. Ink-jet printer head deposits drops of binder* on part cross-section3. Binder dissolves and joins adjacent powder particles4. Table lowered by layer thickness5. New layer of powder deposited above previous layer6. Repeat steps 2-4 till part is built7. Shake powder to get part

*Materials used: starch, plaster-ceramic powder

Three Dimensional Printing (3DP)Three Dimensional Printing (3DP)

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Advantages

1. Easy process

2. Achievable pore size=45–500 um

3. High porosity

4. High surface area to volume ratio

5. Independent control of porosity and pore size

6. Wide range of materials

Disadvantages

1. Use of toxic organic solvents

2. Lack of mechanical strength

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3D printed testpart with interconnecting channels. (a) Whole structure. (b) Detail view of the interconnecting channel structure with diameter of about 500μm.

HA scaffolds seeded with MC3T3-E1 cells

Binder (Schelofix)

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STEREOLITHOGRAPHY

1. Raw material: photocurable monomer by a laser beam

2. Part constructed in layers of thickness

3. Supporting platform in container at depth . UV

laser solidifies part cross- section

4. Platform lowered by

5. Part cross-section computed at current height

6. Repeat Steps 4, 5

7. Removed completed part,

8. Break off supporting structures

9. Cure the part in oven.

He-Cd Laser

UV beam

Rotating mirrorHigh-speedstepper motors

Focusing system

Liquid resin

Part

Platform

Elevation control

Support structures

He-

Ne

Las

er

Sen

sor

syst

emfo

r re

sin

dept

h

Polymerization occurs by the exposure of liquid resin to

laser.

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• Advantages

Relative easy to remove support materials.

Relative easy to achieve small feature.

Disadvantage

Limited by the development of photo

polymerisable liquid monomer material

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Porous polylactide constructsLight microscopy images showing the spreading of mouse pre-osteoblasts after 1 d of culturing on PDLLA network

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SELECTIVE LASER SINTERING

Moving laser beam sinters heat‑fusible powders in areas corresponding to the CAD geometry model one layer at a time to build the solid part

After each layer is completed, a new layer of loose powders is spread across the surface

Layer by layer, the powders are gradually bonded by the laser beam into a solid mass that forms the 3-D part geometry

In areas not sintered, the powders are loose and can be poured out of completed part

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Advantages•High porosity•Achievable pore size=45–200 um•High surface area to volume ratio•Complete pore interconnectivity•Good compressive strengths•Wide range of materials•Solvent free

Disadvantages

•High processing temperatures

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(a) STL design file of porous scaffold. (b) PCL scaffold fabricated by SLS.

cortical shell and areas of trabeculated structures withinthe marrow space

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FUSED DEPOSITION MODELING

FDM uses a moving nozzle to extrude a fibre of

polymeric material (x- and y-axis control) from which the

physical model is built layer-by-layer.

The model is lowered (z-axis control) and the procedure

repeated.

Although the fibre must also produce external structures

to support overhanging or unconnected features that

need to be manually removed

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Z-motion

Melting head withXY-motion

Build materialwire spools:(a) Part (b) Support

Extrusion nozzles

Part

SupportFoam base

Advantages•High porosity•Achievable pore size=250–1000 um•Complete pore interconnectivity •Macro shape control•Independent control of porosity and pore

size•Good compressive strengths•Solvent free

Disadvantage•High processing temperatures•Limited material range•Inconsistent pore opening in x-,y and z-

directions•Requires support structures for

irregular shapes

Materials:ABS, Polycarbonate (PC)

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PCL scaffold with a lay-down pattern fabricated by FDM

HA–PCL scaffolds have a fine apatite coating

3-dimensional distributionof cells within the scaffolds.

PCL HA-PCL

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ORGAN PRINTING (Mironov)

Similar To Ink Jet Printer

Print Gels That Are Thermo responsive

Cells Are Sprayed Onto The Solidifying Thin Layer

Of polymer solution

Poly

mer

Solu

tion

CELL TYPE1CELL TYPE 2

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DISADVANTAGES

Cell Aggregates Are Formed Within Droplet

Cells Maybe Damaged

Choice Of Different Types Of Materials Are

Limited

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(a)Computer aided design-based presentation of model of cell printer.

(b)(b) Bovine aortic endothelialcells were printed in 50-micron size drops in a line.

(c) Cross-section of the p(NIPAAm-co-DMAEA)

(d) Picture of the real cell printer and part of the print head with nine nozzles.

(f) Endothelial cell aggregates ‘printed’ on collagen before

(g)There fusion

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MEMBRANE LAMINATION

Membrane Of 500-2000µm IS USED

It Is Cut By Laser To Form The Shape Required

It Is Then Wet And The Next Layer Is Cut And

Placed On Top Of It And Pressure Is Applied To

Adhere The Two Layers

Then Finally The Solvent Is Evaporated

NOT VERY PRECISE SO MORE PRECISE METHODS ARE NOW REPLACING THIS TECHNIQUE

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TOWARDS NANOTECHNLOGY !!!

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•Cellular interaction with the extracellular matrix is dynamic and demanding.

•Membrane bound receptors are constantly recycled and renew to bind to the matrix.

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NANO FABRICATION TECHNIQUES

ELECTROSPINNING SELF ASSEMBLY

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SELF ASSEMBLY

Self-assembly involves the spontaneous organization of individual

components into an ordered and stable structure with

preprogrammed non-covalent bonds

complex laboratory procedure that is limited to only a select few

polymer configurations (diblock copolymers, triblocks from peptide-

amphiphile, and dendrimers).

The most common of these for the production of nanoscale fibers

are the peptide-amphiphiles (PA).

complexity of the procedure and the low productivity of the method

limit it as a large-scale tissue engineering option

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SAPNS repair for the animal brain. (a) Molecular model of the RADA16-I molecular building block. (b) Molecular model of numerous RADA16-I molecules undergo self assembly to form well ordered nanofibers with the hydrophobic alanine sandwich inside and hydrophilic residues on the outside. (c) The SAPNS is examined by using scanning electron microscopy. (Scale bar, 500 nm.)

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When the electrical force at the surface of a polymer solution or polymer melt overcomes the surface tension, a charged jets is ejected.

ELECTROSPINNING

FIRST DESCRIPTIONElectrospinning was in 1902 when J. F. Cooley filed a United States patent entitled ‘Apparatus for electrically dispersing fibres’

Electro-spinning uses an electrical charge to form a mat of fine fibers.

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Poly styrene fibers

Polyvinyl pyrolidone

fibers

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In summary, biomaterials fabricated by traditional techniques are inadequate for the growth of thick cross-sections of tissue due to the diffusion constraints posed by foam structures.

Rapid prototyping fabrication systems provide a solution to this problem by creating scaffolds with controlled internal microarchitecture, which should increase the mass transport of oxygen and nutrients deep into the structure.

Yet with all these technique available we do not have any guidelines to which type of technique is best for which kind of polymers

The development of new nanotechnology Techniques

to develop better and more promising biomaterials

is on the go

CONCLUSION

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1. The Design of Scaffolds for Use in Tissue Engineering.

Part II. Rapid Prototyping Techniques, TISSUE

ENGINEERING Volume 8, Number 1, 2002.

2. Processing and Fabrication of Advanced Materials VIII

by K. A. Khor, T. S. Srivatsan M. Wang, W. Zhou, F. Boey

on 1999

3. Biomaterials and bioengineering handbook, Donald L

Wiss,2003.

4. Three-dimensional tissue fabrication, Valerie Liu

Tsang, Sangeeta N. Bhatia, Advanced Drug Delivery

Reviews 56 (2004) 1635– 1647

REFERENCES

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THANK YOU