Dr.Sandeep C Agrawal Agrasen Hospital Gondia India www.agrasenortho.com
Dr.Sandeep Agrawal, Agrasen Hospital,
Gondia Maharashtra
India [email protected]
www.agrasenortho.com
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Scaffolds in Tissue Engineering And Stem
Cell Therapy
STEM CELL THERAPY
scaffold
Growth factor(s) cells
Tissue engineering
Dr.Sandeep C Agrawal Agrasen Hospital Gondia India www.agrasenortho.com
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Informations:
!1. What are Scaffolds?!
!2. Some different scaffold design techniques !
A ) Nanofibre Self-Assembly!B ) Gas Foaming!
C ) CAD/CAM technologies!D ) Electro spinning!
!3. Multimedia - Organ Printing Demonstrations!
!4. Future of this technology!
!5. Drawbacks!
!6. Conclusion
Dr.Sandeep C Agrawal Agrasen Hospital Gondia India www.agrasenortho.com
What are Scaffolds?
Scaffolds are structures that are manufactured for the sole purpose of allowing cells to grow.
!Key Elements of Scaffolds and cell development-
Structures that are able to support 3-D cell structures Allow for cell attachment, migration and growth
Enable diffusion of cell nutrients Allow the manipulation of cells to form as correctly shaped tissue
Scaffold
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Principal mechanical supporting structure of any engineered tissue is the SCAFFOLD.
!Ideal scaffold materials for engineered tissues are Resorbable materials that break down over time. During resorption, the engineered tissue is remodeled by normal healing processes, leaving only living cellular tissue with natural supporting
connective tissue. !
Engineered skin substitutes were the first true clinical success of tissue
engineering. 5
Scaffold ..Supporting Structure
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Scaffold purpose
Temporary structural support Maintain shape
Cellular microenvironment High surface area/volume
ECM secretion Integrin expression
Facilitate cell migration
Surface coating
Structural
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Important scaffold variables● Surface chemistry!● Matrix topography!
● Cell organization, alignment!● Fiber alignment -> tissue development!
● Rigidity!● 5-23 kPa!
● Porosity!● Large interconnected!● small disconnected
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Properties of Scaffold
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Ideal Extracellular Matrix● 3-dimensional!● Cross-linked!● Porous!● Biodegradable!● Proper surface chemistry!● Matching mechanical strength!● Biocompatible!● Promotes natural healing!● Accessibility!● Commercial Feasibility
Modulate Properties!Physical, Chemical!Customize scaffold
Appropriate Trade-offs!Tissue!
Disease condition
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Biomaterials for scaffold
⌘ Bicompatible degradation ⌘ Properties can be easily tailored for specific
application ⌘ Mechanical, chemical, structural,
functional ⌘ Various polymer scaffold processing
⌘ Provide ideal growth environment ⌘ Growth factors ⌘ Mechanical stress
Polymer !
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Tissue Engineering
Bio-degradable polymers
bioreactor
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Polymers
Natural polymers Synthetic polymers
Hyaluronic acid-based Poly(glycolic acid) (PGA)
Collagen Poly(L-lactic acid) (PLLA)
Chitosan Poly(DL-lactic-co-glycolic acid) (PLGA)
Fibrin Poly(ethylene oxide) (PEO)
Alginate Poly(ethylene glycol) (PEG)
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⌘ Native polymers ⌘ Proteins (collagen) !!
⌘ Polysaccharides (Hyaluronic acid) !!
⌘ Poly(hydroxyalkonoate)s ⌘ Advantages: ⌘ biocompatibility ⌘ ECM material
⌘ Disadvantages: ⌘ Immunogenic problems ⌘ Isolation ⌘ processability.
Biopolymers:Native
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⌘ Synthetic polymers ⌘ FDA approved biodegradable: Poly(lactic acid),
poly(glycolic acid, poly(ε-caprolactone), poly(trimethylene carbonate), poly(p-dioxanone), and poly(anhydrides).
⌘ Not FDA approved, research only: Poly(phosphazenes), Tyrosine polycarbonate, poly(orthoesters), poly(phosphoesters)
⌘ Poly(methylmethacrylate) ⌘ Poly(tetrafluoroethylene) ⌘ Poly(styrene) ⌘ Polyurethanes
⌘ Advantages: reproducible manufacturing, easy scale-up, readily controlled shape/porosity, ease of chemical modification.
Biopolymers:Synthetic
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FDA Approved
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Materials Science connection: Scaffolds – made by biomaterials
Provide mechanical support for cells Permanent - e.g. extracorporeal therapies
Controlled degradation - scaffolds that go away when they are not needed!
Promoters of cell adhesion, differentiation and function Surface properties
Controlled drug/protein delivery (spatial distribution, release profile, sequential release)
3D structure (morphology affects function)
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Scaffolds can help to signal cell differentiation
Attachment
Proliferation & Differentiation
Tissue Deposition
Tissue maturation
Soluble growth factors
Cell-cell interactions
Mechanical stimuli
Cell-substrate interactionsElectrical stimuli
TimeProcess
seconds
weeks
Substrate
100 nm to 10 cm
ECM HA? Collagen ?
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Additional requirements of scaffold
Biocompatible (regulatory and functional) Processable
Sterilizable (autoclave or UV) Reasonable storage and shelf life
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Scaffolding considerations
Vascular supply
Cell seeding Gradients of growth factors
Spatial gradients of cells
Spatial gradients of materialsdistribution
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Manufacturing scaffolds
⌘ Foams ⌘ Sheets ⌘ Beads ⌘ “Printing” complex 3-D
structures ⌘ (Solid free-form fabrication)
www.therics.com
Conventional method
Pore size, interconnection of pore
Computer – aided method
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Scaffolds
Various textures and materials Encourage cells to grow
Allow nutrients to permeate Won’t harm the patient
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Nanofibre Self-Assembly
!Or molecular self- assembly is one of the
few methods of creating biomaterials. !
This method requires hydro gel scaffolds that cells use to assemble and grow them self as 3-D tissue
structures Can be used in the healing process as these
nanofibres promote the growth and attachment of nerve fibers
Nano fibers break down into nutrients after 2- 3 weeks but their purpose of making cell growth
possible allow for complete cell structures at this time.
Below is a nanofibre structure in which cells will be introduced to grow as a complete organ or bone structure.
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Gas Foaming
This technique allows for a medium to be created in which cells can be introduced to grow.
!Although not as porous as the
Nano fibre structure it is cheaper to create and does assist in
growing strong cell structures.
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CAD/CAM technologies
Cad/cam technologies can be used to create a more complex scaffold structure.
Scaffold design and printing with a computer allow cells to grow and match that of the real organ or bones’ internal
structure. More realistic organ properties
Smaller more precise porous structure Larger cell attachment surface area
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This technique of making scaffolds allows for a more precise finely woven structure.
High voltage is used to create such a densely woven structure for cells to
attach… Allows for more consistent cell growth
Faster reproduction More complex cell structures with nerves
ElectroSpinning
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Future of this technology
In the future, this technology will continue to advance. More and more complex organs will
be able to be created. !
Eventually whole body parts and perhaps whole bodies me be possible to create with this
technology.
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Drawbacks
!With this technology always advancing, ethical issues may
created in the future. One example is if a whole body can be created for transplant, can it not be considered a person?
!Also cost is a factor. This technology is very new and expensive therefore cost must decrease to allow this technology to be viable in a widespread invirnment.
Conclusion
With the further research and engineering, the manufacturing of body parts is becoming more and
more a possibility. From this the possibility of increasing life longevity will become more apparent
as we engineer new ways to replace organs that are failing.
Dr.Sandeep C Agrawal Agrasen Hospital Gondia India www.agrasenortho.com
DisclaimerThis presentation is for orthopaedic doctors and students in general.
. Some graphics and jpeg files are taken from Google and yahoo Image to heighten the specific points in this presentation.
• If there is any objection/or copyright violation, please inform [email protected] for prompt deletion.
• It is intended for use only by the doctors of orthopaedic surgery. . Views expressed in this presentation are personal. • .For any
confusion please contact the sole author for clarification. • Every body is allowed to copy or download and use the material
best suited to him. There is no financial involvement.
• For any correction or suggestion please contact [email protected].
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Like a flower in bloom, the feeling of happiness opens you to a whole new world of possibilities. Leave no room for negatives and focus on what lies ahead. You will be surprised at the
things that you are capable of doing when you are happy!
Happiness opens you to the world of possibilities.
"Happiness and misery depend not upon how high up or low down you are -- they
depend not upon these, but on the direction in which you are tending."
- Samuel Butler
"Laughter is not at all a bad beginning for a friendship,
and it is far the best ending for one."
- Oscar Wilde