The document discusses applications of nanofibers in tissue engineering. It describes three main techniques to produce nanofibers - self-assembly, phase separation, and electrospinning. Several natural and synthetic polymers that can be used to create nanofibers are discussed, including collagen, elastin, polyglycolic acid and polylactic acid. The document also outlines how nanofibers can be applied as scaffolds in tissue engineering and their ability to mimic natural extracellular matrix fibers at the nanoscale level.
Nano Based Polymers and Applications in Drug Delivery
'Anil, A REVIEW : NANOFIBERS APPLICATION
1. A REVIEW : NANOFIBERS APPLICATION
ANIL KUMAR
M.PHIL./PH.D. NANOSCIENCE 2012-13
CENTRE FOR NANOSCIENCE, CUG, GANDHINAGAR SEC-30,
GUJARAT
kmr.nano@indiatimes.com
2. Nanotechnology
• The study of control of matter on an atomic and molecular
scale.
• Deals with structures the size of 100 nanometers or
smaller (1 nm = 1/1,000,000,000 m or 10-9 m).
• Involves engineering on a small scale to create smaller,
cheaper, lighter, and faster devices that can do more
things with less raw materials.
3. NANOFIBERS - INTRODUCTION
ECM fibers ~ 50-500 nm in diameter
Cell ~ several-10 um
Fibers 1-2 orders of magnitude < cell
single cell contacts thousands of fibers
three techniques to achieve Nano-fibers scale
- Self Assembly
-Phase Separation
-Electro-spinning
4. Techniques To Achieve Nano-fibers For TE
Self-assembly
Phase separation
Electrospinning
5. Collagen Fibers
Formed Of Parallel Fibrils
High Modulus Of Elasticity
1.5 nanometers in diameter
300 nanometers long;
20 collagen types that exist in animal tissue
7. Elastin Fibers
• An amorphous protein
• Much lower modulus
of elasticity than
collagen
• Primary constituent of
many ligaments
• Crosslinked
tropoelastin
8. NANOFIBERS: SELF-ASSEMBLY
Definition: spontaneous organization into stable structure without
covalent bonds
Biologically relevant processes
- Cellulose,Lipids, DNA, RNA, protein organization
- can achieve small diameter
Example: peptide-amphipathics
- hydrophobic tail
- cysteine residues disulfide bonds
9. Self-assembly
• Relies on non-covalent interactions to achieve
spontaneously assembled 3D structure.
• Biopolymers such as peptides and nucleic acids
are used. Example is peptide-amphiphile (PA)
• (A) Chemical structure of (PA)
• (B) Molecular model of the PA showing the
narrow hydrophobic tail to the bulkier peptide
region
• (C) Schematic of PA molecules into a cylindrical peptide-amphiphile
micelle.5 Nanofiber
10. Phase Separation
Definition: thermodynamic separation of polymer solution into polymer-rich and
polymer-poor layers
• This process involves dissolving of a polymer in a
solvent at a high temperature followed by a liquid–
liquid or solid–liquid phase separation induced by
lowering the solution temperature
• Capable of wide range of geometry and dimensions
include pits, islands, fibers, and irregular pore
structures
• Simpler than self-assembly
a) powder, b) scaffolds with continuous network, c) foam with closed pores.4
11. Elastin Is An “Entropic Spring”
• ΔG = ΔH – TΔS
• ΔH = enthalpy changes, which don’t normally happen in solvents.
• ΔS = entropy changes…
changes in the degree of
order
• Stretching a polymer
increases it’s order, and
makes ΔS negative.
• ΔG is then positive, and
unfavorable.
12. NANOFIBERS: ELECTROSPINNING
Definition: electric field used to draw polymer stream out of
solution
A- polymer solution in syringe
B- metal needle
C- high voltage applied to need
D- electric field overcomes
solution surface tension;
polymer stream generated
E- fibers 1) collected and
2) patterned on plate
13. NANOFIBERS: ELECTROSPINNING
- multiple polymers can be combined at
1) monomer level
2) fiber level
3) scaffold level
- control over fiber diameter
alter concentration/viscosity
- fiber length unlimited
- control over scaffold architecture
target plate geometry
target plate rotational speed
Current approaches combined techniques
- usually electrospinning + phase separation
- fibers woven over pores
16. POLYGLYCOLIC ACID (PGA)
Properties Parameters
- surface area to volume ratio
- biocompatible
- consistent mechanical properties
hydrophilic
predictable bioabsorption
- electrospinning yields diameters ~ 200 nm
17. Model of Surface-to-volume
Comparisons…
Single Box Ratio
6 m2
= 6 m2/m3
1 m3
Smaller Boxes Ratio
12 m2
= 12 m2/m3
1m 3
• Neglecting spaces between the smaller boxes, the volumes of the box on
the left and the boxes on the right are the same but the surface area of the
smaller boxes added together is much greater than the single box.
19. POLYLACTIC ACID (PLA) – 200 nm
- aliphatic polyester
- L optical isomer used
by-product of L isomer degradation = lactic acid
- methyl group decreases hydrophilicity
- half-life ideal for drug delivery
Parameters (similar to PGA)
- surface area to volume ratio
- spinning orientation affects scaffold elastic modulus
Compare to PGA
- low degradation rate
- less pH change
21. PGA+PLA = PLGA
- tested composition at 25-75, 50-50, 75-25 ratios
- degradation rate proportional to composition
- hydrophilicity proportional to composition
Recent Study
- delivered PLGA scaffold cardiac tissue in mice
- individual cardiomyocytes at seeding
- full tissue (no scaffold) 35 weeks later
- scaffold loaded with antibiotics for wound healing
22. POLYDIOXANONE (PDO)
- crystalline (55%)
- degradation rate between PGA/PLA ,close to 40-60 ratio
- shape memory
- modulus – 46 MPa; compare: collagen – 100 Mpa, elastin – 4 MPa
Advantages
- PDO ½ way between collagen/elastin, vascular ECM components
- cardiac tissue replacement (like PLGA)
- thin fibers (180nm)
24. POLYCAPROLACTONE + PLA
Clinical Applications
- several planned
- all vasculature tissue
- high PLA tensile strength react (constrict) to sudden pressure
increase
- increased elasticity with PCL passively accommodate large fluid
flow
25. ELASTIN
- highly elastic biosolid (benchmark for PDO)
- hydrophobic
- present in: vascular walls, skin
Synthesis of Biosolid?
- 81 kDa recombinant protein (normal ~ 64 kDa)
- repeated regions were involved in binding
- 300 nm (not as small as PDO ~ 180 nm)
- formed ribbons, not fibers – diameter varies
26. COLLAGENS: GELATIN
- highly soluble, biodegradable (very rapid)
- current emphasis on increasing lifespan
COLLAGENS: FIBRIL FORMING
Type I
- 100 nm (not consistent)
- almost identical to native collagen (TEM)
- present is most tissues
Type II
- 100-120 nm (consistent)
- found in cartilage
- pore size and fiber diameter easily controlled by dilution
28. RECONSTRUCTING THE MEDIA
- SMC seeded into tube
- average fiber ~ 450 nm
slightly larger ECM fibers
- incorporation of GAG
carbohydrate ECM
collagen crosslinker
mediate signalling
- cross section of tube wall
- 5 day culture
complete scaffold
infiltration
29. FIBRINOGEN
- smallest diameter (both synthetic and bio)
80, 310, 700 nm fibers possible
- high surface area to volume ratio
increase surface interaction
used in clot formation
Stress capacity comparable
to collagen (80%)
30. HEMOGLOBIN
- hemoglobin mats
- clinical applications:
drug delivery
hemostatic bandages
- fiber sizes 2-3 um
- spun with fibrinogen for clotting/healing
- high porosity = high oxygenation
31. Application of Nano-fibers
• NanoFibers in Tissue Engineering
• NanoFibers in Industrial composite
• NanoFibers in Medicals
• NanoFibers in Filtration
33. Tissue Engineering (TE)
• Scaffolds
Biomaterials, which may be natural or
artificially derived, providing a platform for
cell function, adhesion and transplantation
• Cells
Any class of cell, such as stem or
mesenchymal cell
• Signals
Proteins and growth factors driving the
cellular functions of interest
• Bioreactor
System that supports a biologically active
environment (ex. Cell culture)
Image sourse: Stke.sciencemag.org, Nature.com
35. Fibers use in Filter
Keratin from Wool Nanofibre Non-Wovens
Properties of regenerated wool Nanofibre non-wovens properties
keratin
High surface/volume ratio
Heavy metals absorption [1] High porosity
Formaldeyde absorption [2]
Filtration System
Air Cleaning
Water depuration: especially removal of
ultrafine particles and heavy metals
adsorption
36. Conclusion
COOH COOH
Cells
NH2
Functional Tissue
NH2
COOH Adhesive Proteins
NH2
NH2
Functionalized Nanofiber
Nanofibrous Scaffold
• Physical, Chemical and Biological mimicking enable
various tissue engineering application.
• Tissue engineering holds the promise to develop powerful
new therapies "biological substitutes" for structural and
functional disorders of human health that have proven
difficult or impossible to address successfully with the
existing tools of medicine.
37. Thank You so much
Dean’s :-
Prof. M.H. Fullekar & Prof. Mansingh
Chair Persons:-
Dr. P. Jha
Dr. B. Pathak
Dr. D. Mandal
Friend's :-
M.Phil./Ph.D. Students
Editor's Notes
ABC blocks help students to understand the concept of surface to volume ratios. They need to see the additional surfaces!
