Origami Tissue Engineering

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Overview

thumb|300px|alt=Three different expansion stages of a stent show its structure.|Expansion of a stent [A] Origami Tissue Engineering, just like regular origami, uses planned or calculated folds to produce a three dimensional shape out of a two dimensional plane. By studying folding patterns and applying them to common devices, there is no doubt that they can be greatly improved. For example, stents that are used for clearing up clogged blood vessels, need to start out small (to fit through small passages and catheters), and end up large. Therefore, by knowing an optimal folding pattern, the size of the initial folded stent can be reduced significantly. There are many other similar applications that use efficient fold patterns for biological and medical applications.

History

The art of Origami began in Japan around the Edo Period. Since then, people have been fascinated by the complex three dimensional structures that they could make out of a two dimensional sheet of paper. Artists began to make marvelous masterpieces causing their designs to be more and more complex. For a short amount of time in the mid 1900's, origami seemed to have reached its potential. This was until the involvement of mathematicians. These mathematicians devised intricate models for trying to explain the folding process, and derive different folding patterns. With the use of these new algorithms and models, fold patterns could be optimized to create smaller shapes or shapes with way more detail. Scientist and engineers caught on quickly to the mathematically perfect patterns and began using them for their structures and devices.

  • 1603: Origami evolves as an art form in Japan
  • 1900s: Origami artist begin to create more complex designs
  • 1980s: Mathematicians start applying mathematical models to make even more intricate designs
  • 1990: Robert Lang (Caltech) begins to study and apply these models to every day applications
  • 2003: Zhong You and Kaori Kuribayashi (Oxford Univ.) develop an origami stent
  • 2005: Zhong You and Kaori Kuribayashi innovate their stent so that it is self deployable

Applications

Stents

Traditional wire stent[B]
Traditional wire stent[B]
TiNi foil stent[C]
TiNi foil stent[C]

Kaori Kuribayashi and Zhong You from the university of Oxford, UK have created stents made out of a Ni-rich titanium/nickel foil that utilizes origami folding. Traditional wire stents often result in restenosis due to their porous/mesh nature[4]. The cause of restenosis is due to tissue in-growth through the pores[5]. Therefore, since the TiNi foil is a foil that has no holes, no tissue in-growth can occur. Another great quality of the stents that the have created, is that they deploy automatically. Once the stent reaches the desired destination in the artery or vein, it is pushed out of the catheter where it will expand to its full size without the use of a traditional balloon. The automatic deployment works by two different mechanisms: one is triggered by heat (of the body for example) while the other is triggered solely due to the super elastic behavior of the material[1].

Material Qualities & Preparation
The different etched patterns on the top and bottom of the foil created by negative photoelectric etching.[D]
The different etched patterns on the top and bottom of the foil created by negative photoelectric etching.[D]

This Ni-rich Ti/Ni foil falls under a class of materials called a shape-memory alloy(SMA) which means that the material always wants to return to the shape at which it was cold forged. Having a material be a SMA is ideal for origami engineering since it will want to spring back to its original shape after being folded. Another wonderful property of this material is that it is biocompatable with the body and will induce no negative immune response[6]. The reason why such materials were not used before, is because it was very challenging and expensive to make a TiNi foil (or another biocompatable SMA) so thin while retaining its properties. Now due to research from the early 2000's, it is possible to create such a material relatively inexpensively[1].

To tailor these foils to the temperature of the human body (37.7C) Kuribayashi and You aged the material at 773k for 20-40h[1]. Once the material is aged and ready to be folded, a folding pattern is devised and by using a negative photo-chemical etching process[1]. Following the rules of origami, different patterns were made on either side side of the foil. Once the foil was etched, all that needed to be done to fold the sent was to sub cool it below its Mf (261K) by using liquid nitrogen. Folding occurs the way it does since the foil contracts at cold temperatures and buckles at points where there is less stress. Points of less stress for these stents are the etched lines.

Results

In a simple experiment where a tube the diameter of a catheter was used to implant the stent into a second tube the diameter of an artery, the stent expanded quickly and effectively. In fact the speed of the unfolding was so fast that a high speed camera was needed to capture the motion. The tube that was meant to mimic the artery was preheated to body temperature to make sure that the stent would deploy well at that temperature[1]. Unfortunately this technology has not seen clinical testing yet and it is unknown how well it will work in vivo.

Images from a high speed camera of the TiNi origami stent unfolding.[E]
Images from a high speed camera of the TiNi origami stent unfolding.[E]

Origami Alveoli

Origami alveoli are a model to study the way alveoli work. The reason for using an origami model is that the shape of alveoli changes with time. This requires a model that also can change shape with time, which is also known as a 4D model. First a mathematical model was created that mimicked the motions of each moving part in the alveoli. Next an origami model was built of the duct and the alveoli to be able to visually see the impacts of different conditions.[7]

An origami model for an alveolus[F]
An origami model for an alveolus[F]

Cell Origami

Two different 3D structures created by CTF
Two different 3D structures created by CTF

Scientists from the University of Tokyo, Japan designed an experiment that would created a self folding micro-structure. They named this new method, "Self-Folding Cell Origami". The premise was to use a force that cells exerted naturally, the cell traction force (CTF), in order to make a controlled three dimensional structure. The first step was to design a two dimensional shape that could easily be transformed into a 3D structure. The design that was chosen was a simple cross that would turn into a fully covered square box. Cells were cultured onto a specially designed glass substrate with MPC polymer patterned to effectively guide the folding of the cells. The glass substrate was laid out following a pattern (in this case the cross) since it consists of different rigid segments connected with a flexible hing. Cells were planted so that one cell would be in between two rigid glass segments and directly over the hinge. The cells then, following the designed haptotactic cues began to contract their actin filaments. The way this patterning worked was parts of the glass substrate were coated with the MPC polymer (to which cells cannot adhere to) and other parts were coated with fibronectin (to which cells can adhere to very well). Cells would try to adhere and in the process of looking for good "sticky" spots, they would follow the pattern and encapsulate themselves in the designed box. Cell origami is a good way of studying cells traction forces and behaviors and believed to be the beginning of next generation cell based biohybrid devices for medical applications. [2]

Schematic of the whole process. Below is an image of the actin stained in green and the nucleus in blue
Schematic of the whole process. Below is an image of the actin stained in green and the nucleus in blue

Other Medical Applications

Hydrogel microcapsules folded following and origami pattern[I]
Hydrogel microcapsules folded following and origami pattern[I]

The science of origami folding is also applied to many other areas of medical technologies such as nanomaterials. There are a few studies on origami folding of DNA (called DNA origami) to create different designs that can be used for encapsulating tiny particles. Also, there are studies on precisely folding hydrogel bilayers using origami patterns to create very efficient microcapsules for drugs and other particles[3].

References

  1. K. Kuribayashi et al. Self-deployable origami stent grafts as a biomedical applicationof Ni-rich TiNi shape memory alloy foi. Materials Science and Engineering 2006, A 419, 131-137.
  2. K. Kuribayashi-Shigetomi, H. Onoe and S. Takeuch SELF-FOLDING CELL ORIGAMI: BATCH PROCESS OF SELF-FOLDING 3D CELL-LADEN MICROSTRUCTURES ACTUATED BY CELL TRACTION FORCE. MEMS 2012, 72.
  3. Tae Soup Shim, Shin-Hyun Kim, Chul-Joon Heo, Hwan Chul Jeon, and Seung-Man Yang Controlled Origami Folding of Hydrogel Bilayers with Sustained Reversibility for Robust Microcarrier. Angew. Che 2012, 124, 1449-1452.
  4. E.R. Edelman, C. Rogers, Circulation 94 (1996) 1199–1202.
  5. M. Gottsauner-Wolf, D.J. Moliterno, A.M. Lincoff, E.J. Topol, Clin. Cardiol. 19 (1996) 347–356.
  6. J. Ryhanen, Biocompatibility evaluation of nickel–titanium shape memory metal alloy, in: Dissertation, University Hospital of Oulu, Oulu,1999
  7. H. Kitaoka et al. Origami Model for Breathing Alveol, Advances in Experimental Medicine and Biology, 669, 2010 49-52

IMAGES

[A] <http://www.sciencemag.org.silk.library.umass.edu/content/332/6036/1376/F2.expansion.html>

[B] <http://news.injuryboard.com/johnson-amp-johnson-wins-patent-case-on-heart-stents.aspx?googleid=28948>

[C] K. Kuribayashi et al. Self-deployable origami stent grafts as a biomedical applicationof Ni-rich TiNi shape memory alloy foi. Materials Science and Engineering 2006, A 419, 131-137.

[D] K. Kuribayashi et al. Self-deployable origami stent grafts as a biomedical applicationof Ni-rich TiNi shape memory alloy foi. Materials Science and Engineering 2006, A 419, 131-137.

[E] K. Kuribayashi et al. Self-deployable origami stent grafts as a biomedical applicationof Ni-rich TiNi shape memory alloy foi. Materials Science and Engineering 2006, A 419, 131-137.

[F] H. Kitaoka et al. Origami Model for Breathing Alveol, Advances in Experimental Medicine and Biology, 669, 2010 49-52

[G]-[H] K. Kuribayashi-Shigetomi, H. Onoe and S. Takeuch SELF-FOLDING CELL ORIGAMI: BATCH PROCESS OF SELF-FOLDING 3D CELL-LADEN MICROSTRUCTURES ACTUATED BY CELL TRACTION FORCE. MEMS 2012, 72.

[I]Tae Soup Shim, Shin-Hyun Kim, Chul-Joon Heo, Hwan Chul Jeon, and Seung-Man Yang Controlled Origami Folding of Hydrogel Bilayers with Sustained Reversibility for Robust Microcarrier. Angew. Che 2012, 124, 1449-1452.

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