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ARJUN G NAMBOODIRIPolymer processing Laboratory
4/6/10
BIOMATERIAL FABRICATION TECHNIQUES
OVERVIEW
INTRODUCTION
USE OF BIOMATERIALS
MATERIALS USED AS BIOMATERIALS
EVOLUTION OF BIOMATERIALS
SCAFFOLD FABRICATION TECHNIQUES
LIMITATIONS
RAPID PROTOTYPING
TOWARDS NANOTECHNOLOGY
CONCLUSION
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
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
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
Evolution of Biomaterials
Structural
Functional Tissue Engineering Constructs
(Scaffolds)
Soft Tissue Replacements
First generation
Second Generation
Third Generation
SCAFFOLD FABRICATION TECHNIQUES
Solvent Casting and Particulate Leaching
Melt molding
Gas Foaming
Fiber bonding
Freeze drying
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).
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.
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
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.
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.
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.
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
FIBER BONDING
PGA fibers are immersed in PLLA solution.
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.
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
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.
RAPID PROTOTYPING PROCESSES
Three Dimensional Printing (3DP)
Stereolithography (SLA)
Selective Laser Sintering (SLS)
Fused Deposition Modeling (FDM)
Organ printing
Membrane lamination
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)
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
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)
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.
• Advantages
Relative easy to remove support materials.
Relative easy to achieve small feature.
Disadvantage
Limited by the development of photo
polymerisable liquid monomer material
Porous polylactide constructsLight microscopy images showing the spreading of mouse pre-osteoblasts after 1 d of culturing on PDLLA network
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
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
(a) STL design file of porous scaffold. (b) PCL scaffold fabricated by SLS.
cortical shell and areas of trabeculated structures withinthe marrow space
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
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)
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
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
DISADVANTAGES
Cell Aggregates Are Formed Within Droplet
Cells Maybe Damaged
Choice Of Different Types Of Materials Are
Limited
(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
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
TOWARDS NANOTECHNLOGY !!!
•Cellular interaction with the extracellular matrix is dynamic and demanding.
•Membrane bound receptors are constantly recycled and renew to bind to the matrix.
NANO FABRICATION TECHNIQUES
ELECTROSPINNING SELF ASSEMBLY
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
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.)
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.
Poly styrene fibers
Polyvinyl pyrolidone
fibers
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
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
THANK YOU
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