Electrospinning of Nanofabrics Presented by U6: Pavitra Timbalia Michael Trevathan Jared Walker

Outline Introduction Background Current Research Future Research Apparatus General Applications Current Research Future Research Questions

Introduction Nanofabrics are composed of nonwoven nanofibers Nanofibers are created by a process called electrospinning. Electrospinning is a major way to engineer (without self- assembly) nanostructures that vary in: Fiber Diameter Mesh Size Porosity Texture Pattern Formation Burger, Christian, et. al. Nanofibrous Materials and Their Applications. 2006. http://en.wikipedia.org/wiki/File:Taylor_cone_photo.jpg

Introduction Grafts: Woven vs. Nonwoven The nonwoven structure has unique features: Interconnected pores Very large surface-to-volume ratio Enables nanofibrous scaffolds to have many biomedical and industrial applications. (a) Woven fabrics (b) Non-woven fabrics (c) “Soldered” junctions Burger, Christian, et. al. Nanofibrous Materials and Their Applications. 2006.

An Example Take the distance between the Earth and the Moon, L, to be 380,000 km. It takes only x grams of a polymer fiber filament to make up this distance ρ = 1 g cm-3 and the fiber diameter d = 2r = 100 nm X = Vρ = πr2Lρ = π (50 nm)2 (380,000 km) (1 g cm-3 ) ≈ 3 grams Burger, Christian, et. al. Nanofibrous Materials and Their Applications. 2006.

Electrospinning

Electrospinning - Procedure An electrostatic potential is applied between a spinneret and a collector A fluid is slowly pumped through the spinneret. The fluid is usually a solution where the solvent can evaporate during the spinning. The droplet is held by its own surface tension at the spinneret tip, until it gets electrostatically charged. The polymer fluid assumes a conical shape (Taylor cone). When the surface tension of the fluid is overcome, the droplet becomes unstable, and a liquid jet is ejected Burger, Christian, et. al. Nanofibrous Materials and Their Applications. 2006.

Burger, Christian, et. al. Nanofibrous Materials and Their Applications. 2006.

Burger, Christian, et. al. Nanofibrous Materials and Their Applications. 2006.

Burger, Christian, et. al. Nanofibrous Materials and Their Applications. 2006.

Types of Solvent Stream Ejections Burger, Christian, et. al. Nanofibrous Materials and Their Applications. 2006.

20 wt% Poly(D,L-lactic acid) (PDLA) Nanofibers at voltage of 20 kV, feeding rate of 20 μl min−1 20 wt% Burger, Christian, et. al. Nanofibrous Materials and Their Applications. 2006.

35 wt% Poly(D,L-lactic acid) (PDLA) Nanofibers at voltage of 20 kV, feeding rate of 20 μl min−1 35 wt% Burger, Christian, et. al. Nanofibrous Materials and Their Applications. 2006.

Electrospinning Polymers Solvent Concentration Potential Application Nylon 6,6 Formic Acid 10 wt% Protective Clothing Polyurethanes Dimethylformamide Polycarbonate Dichloromethane 15 wt% Sensor, Filter Polylactic Acid 14 wt% Drug Delivery System The small size between the fibers allows the capture of particles in the 100- to 300- nanometer range That is the same size of viruses and bacteria Used as air-filter: Airplanes, office, etc. Burger, Christian, et. al. Nanofibrous Materials and Their Applications. 2006.

Electrospinning Variables Burger, Christian, et. al. Nanofibrous Materials and Their Applications. 2006.

Applications Burger, Christian, et. al. Nanofibrous Materials and Their Applications. 2006.

Applications Ultrafiltration in water treatment High flux, low-fouling membrane The top layer provides the actual filtration, and the middle and bottom layer provide sting support and are very porous Increased efficiency Able to filter without top layer. Burger, Christian, et. al. Nanofibrous Materials and Their Applications. 2006. Burger, Christian, et. al. Nanofibrous Materials and Their Applications. 2006.

Applications Anti-adhesion in surgery Due to their high surface to volume ratio and being able to conform to different sizes, shapes and textures. Closely match those of native tissue Nanofabrics have been used as scaffolds for tissue and cell regeneration of organs. Burger, Christian, et. al. Nanofibrous Materials and Their Applications. 2006. Burger, Christian, et. al. Nanofibrous Materials and Their Applications. 2006.

Modification, crosslinking, and reactive electrospinning of a thermoplastic medical polyurethane for vascular graft applications Recent Research on Electrospinning

Thermoplastic polyurethanes Used in medical devices and experimental tissue engineering scaffolds Chemical/mechanical properties hard to balance http://www.allproducts.com/manufacture100/tpu/product1.jpg http://www.perfectex.com/tpu01.jpg http://www.pslc.ws/macrog/images/ureth06.gif

Methodology Synthesis of a model compound Modification of thermoplastic polyurethane Pellethane® Modification Reactions Sample prep and crosslinking Swelling behavior Tensile testing Scanning electron microscopy Electrospun grafts Synthesis of a Model Modification Degradation Electrospinning J.P. Theron et al./Acta Biomaterialia

Modification of Thermoplastic Polyurethane http://upload.wikimedia.org/wikipedia/commons/2/25/Sodium-hydride-3D-vdW.png Modified with reactive phenol groups – NaH was added - different amounts to observe changes with the polyurethane Modified polymer was isolated and purified through precipitations in water and vacuum drying Crosslinking achieved by UV light or heat source Swelling index was determined by gravimetric behavior Tensile testing was performed at room temperature and in a cyclical method J.P. Theron et al./Acta Biomaterialia

Scanning electron microscopy Surfaces of the samples – degradation study Pellethane and Pell 15.0 Control samples (not subject to the degradation media) – used as references Determined the amount of degradation on a scale of 1-5 J.P. Theron et al./Acta Biomaterialia

Electrospun grafts Small diameter vascular graft prototypes Used an electrospinning apparatus – high voltage power supply, infusion pump, syringe, rotating/translating mandrel Tubes removed from mandrels by swelling in EtOH and dried Produced crosslinked tubular vascular graft prototype J.P. Theron et al./Acta Biomaterialia

Schematic Representation of the Reactive Electrospinning Apparatus Fibers are irradiated with UV light during spinning in order to form crosslinked graft scaffolds J.P. Theron et al./Acta Biomaterialia

Experimental Results Direct linear correlation between NaH addition and degree of modification By adding the NaH, the research group was able to get between 4.5% and 20% modification of the polyurethane. After 20% modification, samples were discolored/started degrading J.P. Theron et al./Acta Biomaterialia

Experimental Results The range of modifications was tested for mechanical strength The sample which ranked the best was the Pell15.0, or a 15% modified sample. J.P. Theron et al./Acta Biomaterialia

Experimental Results The modified Pell15.0 showed a reduced creep when compared to the Pellethane control – reduction of 44% This is due to the UV crosslinking of Pell15.0. J.P. Theron et al./Acta Biomaterialia

Results Decrease in swelling index with increased degree of modification –an increased modification led to more densely crosslinked material. Crosslinking also showed a decrease in hysteresis as well as breaking stress and strain. The scanning electron microscope showed that the crosslinked samples had only a few cracks, while the control samples had severe surface degradation with deep cracks. The Pell15.0 was spun with UV light into tubular graft structures 40mm in length Grafts diameter (thickness) can be adjusted depending on specific applications J.P. Theron et al./Acta Biomaterialia

Crosslinking improved the resistance to degradation. Pellethane Pell15.0 Before AgNO3 Degrading After AgNO3 Degrading After Hydrogen Peroxide Crosslinking improved the resistance to degradation. J.P. Theron et al./Acta Biomaterialia

Conclusions of this Research Exhibit compliance values within physiological range Can optimize fibers for mechanical, morphological properties, and in vivo response Tissue regrowth, angiogenesis, inflammatory response Manipulate processing conditions Vascular grafts - repetitive, relatively low stress Bio-degradable scaffolds for tissue regeneration Can closely match native tissues - good incorporation in already existing tissue J.P. Theron et al./Acta Biomaterialia http://hairyinterfaces.memphys.sdu.dk/DMueller_fig1.jpg

Surface-functionalized Elecrospun Nanofibers for Tissue Engineering and Drug Delivery Recent Research on Electrospinning

Electrospun Nanofibers High surface area to volume ratio Versatile method for preparing nanofibrous meshes Potential applications: Biomedical devices Tissue engineering scaffolds Drug delivery carriers Done through Surface Modification Plasma treatment Wet chemical method Surface graft polymerization Co-electrospinning of surface active agents and polymers Creates bio-modulating microenvironments to contacting cells and tissues "Surface-functionalized Electrospun Nanofibers for Tissue Engineering and Drug Delivery."

Surface Modification Techniques Synthetic polymers vs. natural polymers Synthetic: easier processing for electrospinning and more controllable nanofibrous morphology Natural: difficult to directly process into nanofibers because of unstable nature and weak mechanical properties Natural polymers can be immobilized onto the surface of synthetic polymers without compromising bulk properties Can incorporate therapeutical agents directly into the nanofibers http://www.animate4.com/nanotech/nanotechnology/nanomedicine/nano/nanoscale/nanotech-nanotechnology-nano-nanomedicine-moleculare-nanotech-nanoscale.jpg "Surface-functionalized Electrospun Nanofibers for Tissue Engineering and Drug Delivery."

Modification – Plasma Treatment Changes the surface chemical composition Selection of plasma source – introduce diverse functional groups on surface Plasma treatments with oxygen, ammonia, or air – generates carboxyl groups or amine groups Air or argon treatments When nanofibers were soaked in a simulated body solution – calcium mineralization occurred on surface Improved wettability Potential with bone grafts http://www.devicedaily.com/wp-content/uploads/2008/11/fortross-02.jpg "Surface-functionalized Electrospun Nanofibers for Tissue Engineering and Drug Delivery."

Modification – Wet Chemical Method Films and scaffolds under acidic or basic conditions – modify surface wettability Plasma treatment can not modify surface of nanofibers deep in the mesh Wet chemical etching methods can modify thick meshes "Surface-functionalized Electrospun Nanofibers for Tissue Engineering and Drug Delivery."

Modification – Surface Graft Polymerization Synthetic biodegradable polymers retain hydrophobic surface – need hydrophilic surface modification for desired response Introduce multi-functional groups on the surface Enhanced cell adhesion, proliferation, and differentiation Initiated with plasma and UV radiation treatment to generate free radicals for polymerization "Surface-functionalized Electrospun Nanofibers for Tissue Engineering and Drug Delivery."

Modification – Co-electrospinning Nanoparticles and functional polymer segments can be directly exposed on surface of nanofibers Co-electrospinning with bulk polymers Any combination of electrospinnable polymer and polymer conjugate can be used "Surface-functionalized Electrospun Nanofibers for Tissue Engineering and Drug Delivery."

Target Molecule Loading on Surface Simple physical adsorbtion Nanopoarticle assembly on surface Layer by layer multilayer assembly Chemical immobilization "Surface-functionalized Electrospun Nanofibers for Tissue Engineering and Drug Delivery."

Applications – Drug Delivery http://www.keystonenano.com/library/images/moleculeAsmall.jpg Applications – Drug Delivery Superior adhesiveness to biological surfaces Variety of structures containing drug molecules Drug release mechanism – polymer degradation and diffusion pathway Can tailor drug release profiles by varying polymer properties, surface coating, combination of polymers Has been successful in laboratory trials – controlled topical release "Surface-functionalized Electrospun Nanofibers for Tissue Engineering and Drug Delivery."

Applications – Tissue Engineering Various cells cultivated on nanofibrous meshes Embryonic stem cells, mesenchymal stem cells Better than other tissue engineering methods Coronary artery cells Collagen Limited to in vitro studies because cells could not be loaded within the nanofibrous meshes in large quantities 3D nanofibrous scaffolds "Surface-functionalized Electrospun Nanofibers for Tissue Engineering and Drug Delivery." http://pcsl.mit.edu/images/nano.jpg

Further Research

Improvements and Further Research Develop more precise electrospinning techniques Mechanisms of electrospinning Growth rates Bending Instability Producing nanofabrics with specific mechanical properties. Creating 3-dimensional shapes Capable of being used in controlled release of drugs. Burger, Christian, et. al. Nanofibrous Materials and Their Applications. 2006.

Improvements and Further Research Optimization of parameters Intrinsic properties of solution Polarity, surface tension of solvent, MW of polymer, etc. Controlling nanofiber alignment Electric field Modifying type of collector Better control of fiber alignment http://www.rsc.org/ejga/NR/2010/b9nr00243j-ga.gif "Electrospin Nanofibers for Neural Tissue Engineering."

Improvements and Further Research Reduce Cost of Production Make economically viable Increase production rate Incorporate the use of an array of spinnerets Safety Solvents Dangerous to health and environment Polymers Burger, Christian, et. al. Nanofibrous Materials and Their Applications. 2006.

References Burger, Christian, Benjamin S. Hsiao, and Benjamin Chu. "Nanofibrous Material and Their Applications." Review. 25 Apr. 2006. Web. 14 Feb. 2010. Hunley, Matthew T., and Timothy E. Long. "Electrospinning Functional Nanoscale Fibers: a Perspective for the Future." Polymer International 57 (2008): 385-89. Web. 7 Mar. 2010. NASA Tech Briefs Create the Future Design Contest. Web. 08 Mar. 2010. <http://www.createthefuturecontest.com/pages/view/entriesdetail.html?e ntryID=1857>. Theron, J. P., J. H. Knoetze, R. D. Sanderson, R. Hunter, K. Mequanint, T. Franz, P. Zilla, and D. Bezuidenhout. "Modification, Crosslinking and Reactive Electrospinning of a Thermoplastic Medical Polyurethane for Vascular Graft Applications." Acta Biomaterialia (2010). 27 Jan. 2010. Web. 05 Feb. 2010. Xie, Jingwei, Matthew R. MacEwan, Andrea G. Schwartz, and Younan Xia. "Electrospin Nanofibers for Neural Tissue Engineering." Nanoscale 2 (2010): 35-44. Print. Yoo, Hyuk S., Taek G. Kim, and Tae G. Park. "Surface-functionalized Electrospun Nanofibers for Tissue Engineering and Drug Delivery." Advanced Drug Delivery Reviews 61 (2009): 1033-042. Print.

Questions

Rebuttal from U6 We agree that we may have used a few too many filler words and will actively try to reduce them in the second presentation One group thought that we should have been more concise, but we felt like we had the right amount of slides to present the topic thoroughly One group would have liked to see a more integrated presentation; we chose to add title slides throughout to let the audience know what we would be discussing next in the presentation Potential further research was discussed in areas which showed promise in the use of nanofibers and the topics which could be researched are endless – one group suggested some additional topics to research Polyurethane is the material which was used to produce the nanofibers, hence is how it is related to the nanotechnology applications We will keep up the quality of the slides since there were a lot of positive comments about them We appreciate all the comments and will take them into consideration for our next presentation

Review of Electrospinning of Nanofabrics Submitted by U1

This presentation particularly caught our attention for its wide range of applications like clothing reinforcement and support for tissue regeneration. Also electrospinning offers the possibility of changing some of the design and material variables to obtain different products makes it very versatile and adaptable for different purposes. Their comparison of different papers that show electrospining base process for the aid of health issues and drug delivery shows that the technology has great future. This presentations was really good overall and meet our expectations. The slides were well constructed and pictures were very helpful in recreating many of the concepts. http://www3.interscience.wiley.com/journal/118859172/issue http://realitypod.com/?tag=artificial

Electrospinning of Nanofabric Review of Group U6’s Presentation- Electrospinning of Nanofabric By Group U2: -Kyle Demel -Keaton Hamm -Bryan Holekamp -Rachael Houk http://www.power.uwaterloo.ca/HVEL/images/Previewtheretical_mod.jpg

The presenters did really well at: Speaking – all presenters in this group were easy to hear and understand Outlining the presentation and going in a logical and easy-to-follow order Giving a thorough introduction Maintaining consistency in text size/fonts Using big and helpful graphics Discussing the articles in detail Other future applications to discuss: Clothing that repels germs, dirt, allergens Clothing with microelectronic nano-generators to produce energy Incorporating microelectronics with three-dimensional tissue engineering Video-imaging on skin Adding nanofabrics to buildings http://gtresearchnews.gatech.edu/newsrelease/power-shirt.htm http://i.ytimg.com/vi/bt-lv6IJPxc/0.jpg http://www.treehugger.com/files/2008/05/nano-vent-skin.php

Electrospinning of Nanofabrics Group 3: Krista Melish James Kancewick Phillip Keller Mike Jones

Presentation Review: Ugrad #6 Material Review Effective job communicating the material I have never heard of electrospinning before, and I was able to follow along and understand what was being presented easily Need to reduce use of verbal distractors (umm, like, etc.) and pauses Always a need to reduce these, but overall the material was communicated clearly Some pictures seemed unnecessary Pictures are nice to have but just including them to fill space (such as on the second further improvements slide) should be limited Instead, condense several points onto a single page Overall Grade: 95 The introduction was concise, yet effective in explaining basic concepts that the research paper looked at further. The graphics used to depict size, demonstrate procedure, and present results were utilized very effectively within the presentation. For example, the process of electrospinning was shown very clearly in your report through the use of several figures. Effective visual format for the material. Questions for further research: Very specific, showing deep thought and breadth of knowledge Good detail in specifying which aspects of electrospinning should receive further attention Good insight considering the safety of the materials used and generated, this subject is generally neglected.

Electrospinning of Nanofabrics Review by Group U4 Burger, Christian, et. al. Nanofibrous Materials and Their Applications. 2006.

Review of Oral presentation and Slides Both presenters were audible from the back of the room Confidence was lacking in the second presenter, sentences were repeated multiple times Presenters, when not presenting should still look engaged not bored staring into space Slides It seemed like information could have been more concise, but it was split up to make the presentation look longer. Pictures on pages were not always related to the information discussed. Everything was well cited Graphs and tables were easy to read and understand http://www.animate4.com/nanotech/nanotechnology/nanomedicine/nano/nanoscale/nanotech-nanotechnology-nano-nanomedicine-moleculare-nanotech-nanoscale.jpg

Technical Content All aspects of electrospinning were described in detail. Research against the subject seemed lacking, and what was done didn’t seem to have a rebutal. Further research was very in depth, present a second paper on the medial uses of electrospinning Very informative, but further research is needed to determine, among others, if it will affect the consumer in a negative way. Burger, Christian, et. al. Nanofibrous Materials and Their Applications. 2006.

Review of Electrospinning of Nanofabrics Review of Group U6 by Group U5 58

Oral and Quality of Slides Speakers had very good oral presentation skills. Clear, confident, and knowledgeable in their discussion. Font size and pictures were appropriately sized and well cited.

Technical Review Very sound technical report. Appeared to have extensive and relevant research. Would have liked to see a more integrated presentation, instead of segmented by paper titles.

Review for U6 Jung Hwan Woo

I didn’t clearly understand how the thermoplastic polyeurethane is related to the nanotechnology. Is this material a type of “nanofibers” described earlier in the presentation? The connection between these will help improve the presentation. How is the homogeneity achieved during the co-electrospinning? Is this something that must be controlled? Does it have an impact on the final product?