scaffolds in stem cell therapy dr.sandeep c agrawal agrasen hospital gondia india

Dr.Sandeep C Agrawal Agrasen Hospital Gondia India www.agrasenortho.com

Dr.Sandeep Agrawal, Agrasen Hospital,

Gondia Maharashtra

India drsandeep123@gmail.com

www.agrasenortho.com

Scaffolds in Tissue Engineering And Stem

Cell Therapy

STEM CELL THERAPY

scaffold

Growth factor(s) cells

Tissue engineering

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

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

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

Scaffold purpose

Temporary structural support Maintain shape

Cellular microenvironment High surface area/volume

ECM secretion Integrin expression

Facilitate cell migration

Surface coating

Structural

Important scaffold variables● Surface chemistry!● Matrix topography!

● Cell organization, alignment!● Fiber alignment -> tissue development!

● Rigidity!● 5-23 kPa!

● Porosity!● Large interconnected!● small disconnected

Properties of Scaffold

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

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 !

Tissue Engineering

Bio-degradable polymers

bioreactor

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)

⌘ Native polymers ⌘ Proteins (collagen) !!

⌘ Polysaccharides (Hyaluronic acid) !!

⌘ Poly(hydroxyalkonoate)s ⌘ Advantages: ⌘ biocompatibility ⌘ ECM material

⌘ Disadvantages: ⌘ Immunogenic problems ⌘ Isolation ⌘ processability.

Biopolymers:Native

⌘ 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

FDA Approved

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)

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

Substrate

100 nm to 10 cm

ECM HA? Collagen ?

Additional requirements of scaffold

Biocompatible (regulatory and functional) Processable

Sterilizable (autoclave or UV) Reasonable storage and shelf life

Scaffolding considerations

Vascular supply

Cell seeding Gradients of growth factors

Spatial gradients of cells

Spatial gradients of materialsdistribution

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

Scaffolds

Various textures and materials Encourage cells to grow

Allow nutrients to permeate Won’t harm the patient

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.

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.

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

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

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.

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.

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 drsandeep123@gmail.com 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 drsandeep123@gmail.com.

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scaffolds in stem cell therapy dr.sandeep c agrawal agrasen hospital gondia india

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