INVESTIGATION AND PRODUCTION OF

BIODEGREDABLA NANOFIBERS AND

THEIR PROPERTIES

FALL TERM MASTER PROJECT

Submitted by: Aybala OZCAN

Submitted to:Prof.Dr.Ali KIRECCI

APPENDIX

• Introduction

• Biodegradable Nanofibers

• Usage Areas Of Biodegradable Nanofibers

• Biodegradable Polymers

• Synthetic Biodegradable Polymers

• Natural Biodegradable Polymers

• Techniques

• Usage Areas

• Conclusion

INTRODUCTION

The development of a viable

nanotechnology passes through the

development of processing

techniques, which can be used in

desired production scales with

reproducibility, especially in the

cases where the final product is still

in the nanoscale.

Biodegradable Nanofibers

Biodegradable nanofibers ;

contains the absorbent particules which are containing

antibodies to numerous biohazards and chemicals

and they are very compatible with human body,cell or

tissue due to consist of biopolymers such as does not

harmfull the biological and environmental system ,

widely known for its wound healing, anti-tumor,

antioxidant, and anti-inflammatory properties, were

prepared via electrospinning method.

Usage Areas of Biodegradable Nanofibers

- tissue engineering

neural repair

cell-based therapeutics

- medical and pharmaceutical applications

- composites and resins

- agriculture applications

- air filtration

Synthetics

Polycaprolactone(PCL)

Polylactic acid (PLA)

Polyglycolic acid (PGA)

PGA-PLA

Polydioxanone (PDO)

Polycaprolactone-Polylactic Acid

(PCL-PLA)

Polydioxanone-Polycaprolactone

(PDO-PCL)

Naturals

Elastin

- Gelatin collagen

- Fibrillar collagen

- Collagen blends

- Fibrinogen

-Polysaccharides

BIODEGRADABLE POLYMERS:

Both of the synthetics and natural polymers may be referred

to use for production of biodegradable nanofibers.

SYNTHETIC POLYMERS

POLYGLYCOLIC ACID (PGA)

- biocompatible

- consistent mechanical properties

hydrophilic

predictable bioabsorption (2-4 weeks)

- electrospinning yields diameters ~ 200 nm

Random fiber collection (L), aligned collection (R)

POLYLACTIC ACID (PLA)

SYNTHETIC POLYMERS

- aliphatic polyester

- methyl group decreases hydrophilicity

- predictable bioabsorption, slower than PGA (30 wks)

- half-life ideal for drug delivery

(POLYGLYCOLIC ACID+ POLYLACTIC ACID)

PGA+PLA = PLGA

-tested composition at 25-75, 50-50, 75-25

ratios

- degradation rate proportional to composition

- hydrophilicity proportional to composition

Thickness controlled by electrospin solvent

Both fibers randomly collected(PLA)

SYNTHETIC POLYMERS

POLYDIOXANONE (PDO)

- crystalline (55%)

- degradation rate between PGA/PLA

- shape memory

POLYCAPROLACTONE (PCL)

-highly elastic

- slow degradation rate (1-2 yrs)

- similar stress capacity to PDO,

higher elasticity

•Advantages

- overall better for cardiac tissue – no

shape retention.

SYNTHETIC POLYMERS

POLYDIOXANONE-POLYCAPROLACTONE

(PDO-PCL)

- PGA high stress tolerance

- PCL high elasticity

- optimized combination PGA/PCL ~ 3/1

- bioabsorption at least 3 months.

POLYCAPROLACTONE-POLYLACTIC ACİD

( PCL-PLA)

PLA highly biocompatible (natural by products)

- PCL high elasticity

- more elastic than PGA/PCL

- strain limit increases 8x with just 5% PCL

NATURAL POLYMERS

ELASTIN

- highly elastic biosolid (benchmark for PDO)

- hydrophobic

- present in:vascular walls,skin

COLLAGENS: GELATIN

highly soluble, biodegradable (very rapid)

- current emphasis on increasing lifespan

NATURAL POLYMERS

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

NATURAL POLYMERS

COLLAGENS BLENDS

In context: vasculature

- intima – collagen type IV + elastin

- media – thickest, elastin, collagen I, III, SMC

- adventia – collagen I

NATURAL POLYMERS

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

HEMOGLOBIN

hemoglobin mats

- clinical applications:

drug delivery

hemostatic bandages

- fiber sizes 2-3 um

- spun with fibrinogen for clotting/healing

- high porosity = high oxygenation

NATURAL POLYMERS

Biodegradable nanofibers microscope allignment based on

hemoglobin.

NATURAL POLYMERS

POLYSACCHARIDES

Cellulose acetate (CA), a derivative of cellulose, has

also been electrospun into ultrafine fibers using

acetone or acetone/water as solvent.

Additionally, electrospun CA fibers have also been

used in cosmetics ,drug delivery ,protein detection,

bactericide and bio-scaffolding applications.

Chitin is the second most abundant naturally

occurring polysaccharide after celluose, and it can be

readily obtained from the shells of arthropods, such as

crabs and insects.

TECHNIQUES

Three methods are available to produce biodegradable

nanofibers which are electrospinning,self-assembly and

Phase seperation method.

The availability of a wide range of natural and

synthetic biomaterials has broadened the scope for

development of nanofibrous scaffolds, especially

using the electrospinning technique.

1-Electrospinning Method

Electrospinning represents

an attractive technique for

the processing of polymeric

biomaterials into nanofibers.

This technique also offers

the opportunity for control

over thickness and

composition of the nanofibers

along with porosity of the

nanofiber meshes using a

relatively simple experimental

setup.

Image courtesy of Reneker

Group –

The University of Akron,

College of Polymer Science

and Samantha Loutzenheiser,

Hoover High School

New yarns with outstanding

wicking properties: Here

electrospun PLGA fibers are

spun into yarns.

• Parameters influencing on electrospinningprocess

-Solution properties, such as concentration

viscosity,elasticity,conductivity,volatility of the solvent,

and surface tension.

-Processing parameters,such as applied voltage,tip

collector distance,electric field strength,needle tip

design,collector composition and geometry ,and flow-rate.

-Ambient parameters,such as temperature,humidity,and

air velocity.

-Aligned fibers.

-Rotating mandrels.

2-Self-Assembly Method

Definition: spontaneous organization into stable structure without

covalent bonds

Biologically relevant processes

- DNA, RNA, protein organization

- can achieve small diameter

Drawbacks: more complex in vitro limited to

1) several polymers and

2) hydrophobic/philic interactions

Example: peptide-amphiphiles

- hydrophobic tail

- cysteine residues disulfide bonds

Schematic illustration of the self-assembly process of peptide-

amphiphiles functionalized to form a nanofiber 7.6 ± 1 nm in

diameter.

3-PHASE SEPERATİON METHOD

Definition: thermodynamic separation of polymer solution into

polymer-rich/poor layers

- similar to setting a gel

- control over macroporous architecture using porogens, microbeads,

salts 98% porosity achieved.

- consistent

Drawbacks:

- limited to several polymers

- small production scale

Process Advantages Limitations

Self -Assembly Achieves fiber diameters o

lowest scale (5-8 nm)

• Only short fibers can be

created.(<1 nm)

•Low yield.

•Matrix directly fabricated.

•Limited to a few polymers.

Phase Seperation • Tailorable mechanical

properties,pore size and

interconnectivity.

•Batch-to-batch

consistency.

• Low yield

•Matrix directly fabricated

•Limited to a few polymers

Electrospinning • Cost effective

•Long continuous

nanofibers

•Production of aligned

nanofibers

•Tailorable mechanical

porpertiesiszeishape

•Plethore of polymers may

be used

• Large nanometer to

micron scale fibers

•Use of organic solvents

•No control over 3D pore

structure

OVERVIEW

- Electrospinning viable for both synthetic and biological scaffolds/mats

- Wide range of fiber sizes necessary and possible

ECM ideally 150-500 nm

cell mats 2-3 um

- Hybridizing polymers can, but not necessarily, lead to hybrid properties

Specifics:

- PGA, PLA, PLGA most commonly used scaffold materials

- PDO exhibits elastin+collagen functionality in 1 synthetic polymer

BUT inhibited by “shape memory”

- PCL most elastic synthetic – frequently mixed with other synthetics

Tissue Engineering

Tissue engineering approaches make use of

biomaterials, cells, and factors either alone or in

combination to restore or regenerate, maintain, or improve

tissue function.

The scaffold gradually degrades with time to be

replaced by newly grown tissue from the seeded cells

(Langer and Vacanti 1993).

Biodegradable nanofibers, irrespective of their

method of synthesis, have been used as scaffolds for

musculoskeletal tissue engineering (including bone,

cartilage,ligament,and skeletal muscle), skin tissue

engineering, vascular tissue engineering,neural tissue

engineering, and as carriers for the controlled delivery

of drugs, proteins, and DNA.

Genetically engineered cells can be used as therapeutics.

using of biodegradable nanofibers are becoming rising stars

in Cell-based therapeutics for tissue engineering and cell-

replacement therapy because of their pluripotency ,self-

renewal capability and compatible with body.

Tissue Engineering

-Techniques and Polymers

Both self-asemmbly and phase seperation techniques

have been used succesfully to fabricate nanofibers for tissue

engineering.

However,in comparison,electrospinning is widely used by

researchers because of the simplicity,diversity and control

over scaffold geometries and mechanical characteristics,the

easily scaling-up property.

Tissue Scaffolding:

Fibroblast cells grown

on PLGA nanofibers

Image by Amy Liu, Hoover High School Student

Both synthetic polymers,such as polyglycoli acid(PGA),polylactic

acid(PLA),polycaprolactone (PCL) and their blends of

copolymers,and natural polymers such as elastin and collagens,have

been exploited.

Techniques And Polymers

Biodegradable polymeric nanofibers are of great

interest as scaffolds for tissue engineering and

drug delivery due to their extremely high surface

area, high aspect ratio and in structure to the

extracellular matrix (ECM) is the meaning of structural

material between cells and referred as connective tissue.

Agriculture Applications

Electrospinned biodegradable nanofibers from

different biodegradabla polymers,as PVA and

PLA are used,and titaniumdioxide is also used to

improve antibacterial and catalytic activities of

nanofibers in agriculture applications.

- Medical And Pharmaceutical Applications

The biodegradable nanofibers which are formed by

electrospinning fibers of biodegradable fiberizable

material,comprise a composite of different biodegradable

fibers.

These nanofibers having special medical uses include an

adhesion-reducing barrier and a controlled delivery system.

The methods include methods for reducing surgical

adhesions,controlled delivery of a medicinal agent and

porviding controlled tissue healing.

CONCLUSION

Usage area of biodegradable nanofiber is especially a rising

star of tissue engineering and drug delivery technlogy.

Biodegradable polymers such as PLGA and PCL have

already been electrospun into nanofibers, and nerve

guidance conduits have been fabricated using these

materials.

The ability of scaffolds to support biodegradable

nanofibers combined with good mechanical

prperties,biocompatibility and tuneable biodegradable

properties of the scaffold suggest their potential use for

tissue engineering.

References

1-W. J. Li, C. T. Laurencin, E. J. Caterson, R. S. Tuan, and F. K. Ko. J. Biomed. Mater. Res.60 [41,613. (2002).

2-L.S.Nair, S. Bhattacharyya, J.D. Bender, Y.E.Greish, P.W. Brown, H.R. Allcock, and

C.T.Laurencin. Biomacromolecules 5, 2212-2220 (2004).

3-J. Groll, W. Haubensak, T. Ameringer, M. Moeller, Ultrathin coatings from isocyanate star PEG prepolymers: patterning of proteins on the layers., Langmuir, 2005, 21(7), 3076-3083.

4-Biodegradable Cell-Seeded Nanofiber Scaffolds forNeuralRepair-Dong Han&Karen C. Cheung-Polymers 2011, 3, 1684-1733; doi:10.3390/polym3041684

5-Biodegradabla Nanofibers and Implementations theory-US 2012/0135234 A1,May 31 2012

6-Biodegradable and/or Bioabsorbable Fibrous Articles and Methodsfor

Using The Articles for Medical Applications,Us 7.172,765

B2,Feb.6,2007( The Research Foundation of State University of New

York,Stony Brook,NY(S) .)

7-Development of Biodegradable Polyphosphazene-

Nanohydroxyapatite Composite Nanofibers Via Electrospinning

Department of Chemical Engineering, The University of Virginia,

Charlottesville, VA-22904 6Department of Biomedical Engineering,

The University of Virginia, Charlottesville, VA-22908.(2005)

8-Biodegradable Nanofiber Mesh for Tissue Engineering

Erica Brown 1, Margaret W. Frey 2, Mary Rebovich 2

Department of Chemical, Biological, and Materials

Engineering, University of Oklahoma, Norman, OK 73019 1

Department of Textiles and Apparel, Cornell University, Ithaca,

NY 14853.

9-Biomedical Pathces With Aligned Fibers-Wo 2011/159889

A2,Washington University,One Brookings

Drive,St.Louis,MO 63130(US).

10-Biodegradable polyesters reinforced with triclosan loaded

polylactide micro/nanofibers:Properties, release and

biocompatibility L. J. del Valle,* A. Díaz, M. Royo, A.

Rodríguez-Galán, J. Puiggalí

11-role of Nanomedicines in Cell-Based Therapeutics-

Zhaoyang Ye & Ram I Mahato,the Johns Hopkins

University,Department of biomedical

engineering,Baltimore,USA.

12-Biodegradable Polymers:Past,Present,and Future. M.

Kolybaba1, L.G. Tabil 1, S. Panigrahi1, W.J. Crerar1, T.

Powell1, B. Wang1Department of Agricultural and

Bioresource Engineering University of Saskatchewan.

13-Nanofiber Technology: Designing The Next Generation Of

Tissue Engineering Scaffolds. C.P. Barnes, S.A. Sell, E.D.

Boland, D.G. Simpson, G.L. Bowlin

Department of Biomedical Engineering, Department of

Anatomy and Neurobiology Virginia Commonwealth

University, Richmond, VA.

Thanks for your interest