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Nanotechnology on Tissue

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Nanotechnology for tissue engineering: Need, techniques and applications
Impact Factor: 2.89 · DOI: 10.1016/j.jopr.2013.02.021





J. Danie Kingsley

Shivendu Ranjan

VIT University

VIT University





Nandita Dasgupta
VIT University

Available from: Shivendu Ranjan
Retrieved on: 14 March 2016

j o u r n a l o f p h a r m a c y r e s e a r c h x x x ( 2 0 1 3 ) 1 e5

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Review Article

Nanotechnology for tissue engineering: Need, techniques and applications
J. Danie Kingsley, Shivendu Ranjan*, Nandita Dasgupta, Proud Saha
School of Bioscience and Technology, VIT University, Vellore 632014, Tamil Nadu, India

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Tissue engineering is very fast growing scientific area in this era which is used to create,

Received 1 December 2012

repair, and/or replace cells, tissues and organs by using cell and/or combinations of cells

Accepted 27 February 2013

with biomaterials and/or biologically active molecules and it helps to produce materials

Available online xxx

which very much resembles to body’s native tissue/tissues. From tissue engineering current therapies got revolutionised and life quality of several millions patient got


improved. Tissue engineering is the connecting discipline between engineering materials


science, medicine and biology. In typical tissue engineering cells are seeded on


biomimicked scaffold providing adhesive surfaces, then cells deposit their own protein to


make them more biocompatible, but unable to vascularise properly, lack of functional cells,


low mechanical strength of engineered cells, not immunologically compatible with host

Tissue engineering

and Nutrient limitation are a classical issue in the field of tissue and tissue engineering.
Through the article we will understand the technology involved, need and application of nanobiotechnology based tissue engineering.
Copyright ª 2013, JPR Solutions; Published by Reed Elsevier India Pvt. Ltd. All rights reserved. 1.


Tissue engineering is very fast growing scientific area in this era and used to create, repair, and/or replace cells, tissues and organs by using cell and/or combinations of cells with biomaterials and/or biologically active molecules and helps to produce materials which very much resembles to body’s native tissue/tissues. Tissue engineering is the connecting discipline between engineering materials science, medicine and biology.1 In typical Tissue engineering cells are seeded on biomimicked scaffold providing adhesive surfaces, and then cells deposit their own protein to make them more

biocompatible, but unable to vascularise properly, lack of functional cells, low mechanical strength of engineered cells, not immunologically compatible with host and Nutrient limitation are a classical issue in the field of tissue and tissue engineering.2 “Novel biomimetic scaffold” and “Modern technology” been developed for more accuracy on positioning and viability, complexity, interaction etc., using micro and nanotechnology for production and analytical control through tools.3 Micro and nanotechnology are providing them simple substrate for adhesion and proliferation and active agents for their growth. Nanofabrication techniques, materials science, surface, micro and nano-patterning in tissue engineering

* Corresponding author. Tel.: þ91 9566763718.
E-mail address: (S. Ranjan).
0974-6943/$ e see front matter Copyright ª 2013, JPR Solutions; Published by Reed Elsevier India Pvt. Ltd. All rights reserved. Please cite this article in press as: Danie Kingsley J, et al., Nanotechnology for tissue engineering: Need, techniques and applications, Journal of Pharmacy Research (2013),


j o u r n a l o f p h a r m a c y r e s e a r c h x x x ( 2 0 1 3 ) 1 e5

Fig. 1 e Schematic representation of benefits of using micro and nanofabrication for tissue engineering.

helps in providing best microenvironment where cells have to grow.4 2.

Tissue engineering from nanotechnology

There are several benefits of using micro and nanofabrication techniques for tissue engineering (Fig. 1). Nanotechnology can be used to create nanofibers, nanopatterns and controlledrelease nanoparticles with applications in tissue engineering, for mimicking native tissues since biomaterials to be engineered is of nanometre size like extracellular fluids, bone marrow, cardiac tissues etc.5


Various nanostructures found naturally in the body (Fig. 2).
Basement membrane for adhesion and affects other cellular behaviour is of 5e200 nm9 (Fig. 3). Chemically cell density increases when poly(lactic-co-glycolide) nanosurface is treated with NaOH.10 E-beam lithography is useful in nano tissue engineering.11 Nanotechnology helps to improved regulation of cell adhesion and vascularisation e.g. compatible epithelial basement membrane like structure formed from carbon nanotube in osteoblast cells adhesion also nanofibres on glass as substrate used for same but earlier one is more efficient.12


Nanotextured substrates for tissue engineering

Self-assembled nanomaterials

Electrospun nanofibers

It is the tools for form biomimic scaffold, and used for bone, cardiac muscle tissue engineering. To guide cell orientation and form blood vessel-like structures aligned poly(L-lactic-co-ε-caprolactone) nanofibres were used.6 Using poly(lactic- co -glycolide) and poly(L-lactic acid) scaffolds neural stem cells were studied7 and these fibres are able to control scaffold function i.e. biomimicked the adhesion surface, also nanofibres with coreeshell structure were used for “Controlled Release” of encapsulated molecules.8

Methods for inducing self assembly in tissue engineering are biomimetic coating, electrolytic deposition (ELD) and pH induction and many materials used such as peptide amphiphile
(PA), hyaluronan, chitosan, and apatite/amelogenin.5,13 Sheets/ fibres of self assembled peptides formed because of hydrophobic and hydrophilic regions and further assembly is because of charge shielding in the form of hydrogels.5,14 High aspect ratio nanofibres in 3D self assembled fibres are made possible by using PA which is used in controlled release of bone morphogenetic proteineprotein but having less cellecell

Fig. 2 e Size scale of various biological structures.
Please cite this article in press as: Danie Kingsley J, et al., Nanotechnology for tissue engineering: Need, techniques and applications, Journal of Pharmacy Research (2013),

j o u r n a l o f p h a r m a c y r e s e a r c h x x x ( 2 0 1 3 ) 1 e5


Fig. 3 e Basic series of events during tissue engineering and implantation.

attachment, which could be overcome by branched PA associated with Phosphoglyceric acid (PGA) conjugated with arginine-glycine-aspartic acid (RGD).15 ELD is also used to develop nano structure which is used for the crystal growth of the collagen fibres at cathode, so it has vast application in osteotherapy and bio-compositing enamels16 and coating with self assembled amelogenin and calcium phosphate and also used to study bone marrow stromal cell attachment.17



From the above discussion we can conclude that tissue engineering is easier through nanotechnology using nanophase materials in comparison of conventional methods (Fig. 4) and is used in many of the fields for different purposes.

Stem cells tissue engineering through micro and nanotechnology Techniques used are as: (i) Electrospinning help to improve adhesion and expansion of hematopoietic stem/progenitor cell at animated nanofiber mesh18 and in Bone marrow these acts as efficient captor and carrier for hematopoietic stem cells.19 (ii)
Soft lithography is used in regulating the distribution, alignment, proliferation, and morphology of Human Mesenchymal stem cells,20 initiation of differentiation of embryoid bodies of greater uniformity in cell culture in vitro,21 ease to study the growth and differentiation of human Embryonic Stem Cells under defined conditions and homogeneous aggregation of

human embryonic cells.22 (iii) Photolithography to maintain the cells to be in the grooves not ridges and maintaining uniform shape and it also have affects the rate of lipid production and thus differentiation of cells to adipocytes.23

Neural cells tissue engineering through micro and nanotechnology Techniques used are as: (i) Electrospinning helps in cell differentiation, orientation and behaviour like embryoid bodies will differentiate into mature neural lineage cells including neurons, oligodendrocytes, and astrocytes when they will be cultured on polycaprolactone,24 poly (L-lactic acid) nanofibers neural stem cells differentiation is more7 (Yang F et al; 2005).
(ii) Replica moulding helps in maintaining cell shape and behaviour e.g. bovine aortic endothelial cells can be cultured with higher cell alignment frequency and smaller circular index when they are culture on “Poly(glycerolesebacate) on sucrose-coated microfabricated silicon”25 (iii) Microcontact printing helps to form synaptic connections on defined protocol with polystyrene and polydimethylsiloxane26 also rat hippocampal neurons when cultured with silicon oxide showed resting potential and after 1 day of culture they become capable to reach action potential.27

Cartilage cells tissue engineering through micro and nanotechnology Techniques are as: (i) Photolithography used to maintain cell behaviour e.g. Chondrocytes isolated from avian sterna

Fig. 4 e Schematic representation about superiority of the tissue engineering through nanotechnology than conventional one. (Courtesy: Daniela Coutinho et al; Tissue Engineering; 2011; 3e29).
Please cite this article in press as: Danie Kingsley J, et al., Nanotechnology for tissue engineering: Need, techniques and applications, Journal of Pharmacy Research (2013),


j o u r n a l o f p h a r m a c y r e s e a r c h x x x ( 2 0 1 3 ) 1 e5

were cultured on micropatterned agarose gel which acts as biomomicked scaffolds and helps in maintaining chondrogenic phenotype28 (ii) Replica moulding helps to maintain controlled microenvironment and is integrated with inverted microscope to monitor real-time for cell size change in articular chondrocyte.29

Bone cells tissue engineering through micro and nanotechnology Techniques used are as: (i) Soft lithography used to maintain cell orientation and behaviour e.g. mesenchymal osteoprogenitor cells are cultured on collagen and thus appropriate surface topography enhances bone formation.30 (ii) Photolithography is providing better groove topography for primary human osteoblasts and helps in cellular adhesion and osteospecific function and in determining cellular response also used in “patterned cell cocultures” for Human osteogenic sarcoma cells on Photocrosslinkable chitosan by using lysozyme.31 (iii) Microcontact printing helps in osseointegration of
Rat mesenchymal stem cell-derived osteoblasts cultured on poly(3-hydroxybutyrate-co-3-hydroxyvalerate) which can guide selective osteoblast adhesion and alignment.32 (iv)
Electrospinning- starch/polycaprolactone nanofiber induces cell morphology to stretch and further increases activity, and viability in Human osteogenic sarcoma cells culture.33

Vascular cells tissue engineering through micro and nanotechnology Techniques used are as: (i) Soft lithography helps to induce global gene expression and alteration in cell signalling in mesenchymal stem cells’ culture with polydimethylsiloxane34 and also helps to increase retention of endothelial cells with poly-urethane which results in reducing thrombogenicity during its implantation.35 (ii) Microfluidic patterning helps to form contractile cardiac organoids from cardiomyocytes with the help of hyaluronic acid36 and helps in cell-ligand attachment and spatial distribution for culturing human umbilical vein endothelial cells with poly(ethylene glycol).37
(iii) Microcontact printing helps to respond differently with shear stress for Bovine aortic endothelial cells’ culture with polydimethylsiloxane.38 (iv) Electrospinning helps in attachment and migration of cells along the axis in human coronary artery smooth muscle cell culture with poly(L-lactid-coε-caprolactone).6

Hepatic cells tissue engineering through micro and nanotechnology Techniques used are as: (i) Electrospinning promotes the formation of integrated spheroidenanofiber construct in rat primary hepatocytes culture with poly(e-caprolactone-coethyl ethylene phosphate.6 (ii) Soft lithography along with some defined design help to provide sufficient oxygen and nutrient mass transfer to maintain viability in hepatoma cells culture and primary rat hepatocytes culture with polydimethylsiloxane and polycarbonate.39 (iii) Photolithography helps to maintain cellecell 3D structure in hepatocytes culture with poly(ethylene glycol)40 and also able to maintain

phenotypic functions for many weeks in primary rat hepatocytes and primary human hepatocytes culture with polydimethylsiloxane.41 Conflicts of interest
All authors have none to declare.


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Please cite this article in press as: Danie Kingsley J, et al., Nanotechnology for tissue engineering: Need, techniques and applications, Journal of Pharmacy Research (2013),

j o u r n a l o f p h a r m a c y r e s e a r c h x x x ( 2 0 1 3 ) 1 e5

17. Wang J, Apeldoorn A, Groot K. Electrolytic deposition of calcium phosphate/chitosan coating on titanium alloy: growth kinetics and influence of current density, acetic acid, and chitosan. J Biomed Mater Res A.
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22. Khademhosseini A, Ferreira L, Blumling III J, et al. Co-culture of human embryonic stem cells with murine embryonic fibroblasts on microwell-patterned substrates. Biomaterials.
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Please cite this article in press as: Danie Kingsley J, et al., Nanotechnology for tissue engineering: Need, techniques and applications, Journal of Pharmacy Research (2013),

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...may enter our bloodstream or our biological system with no noticeable effects. Nanobots can also be used to fix environmental problems such as pollution, and can be used as industrial manufacturing and other major problems. These tiny robotic machines may be the key to our biggest problems on earth.  Medical institutes use nanotechnology for numerous reasons. Since these robots are so small, they can be inserted into a person’s biological system without any noticeable effects. They are so small, in fact, that they may be the same size as blood cells. They can either be remotely controlled or pre-programmed for a certain procedure or a specific purpose. They could, theoretically, be programmed to seek out and destroy cancer cells and completely remove them without the need for lengthy treatments.  They could also be employed to repair and reconstruct damaged tissue on the cellular level.  This would also have the effect of slightly increasing a person’s own healing ability. No matter how damaged a portion of a person’s body may be, these nanobots might be able to repair them and quickly.  Following this same concept, we can apply the use of nanotechnology to much bigger problems.  Pollution has become a major concern in recent years and there seems to be no real working solution to the problem. Hazardous chemical releases from things such as factories and cars are released into the atmosphere where they will often remain for decades.  Since nanobots have the ability to......

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...ISSUES PAPER Date 28 March 2008 Subject ISSUES PAPER: Emerging Technology Table of Contents Introduction 1 Communications Technology 2 Green City 2 Nanotechnology 2 Personalized Medical Monitors 2 Robotics 2 Mind-controlled interfaces 3 Personal Networking 3 Smart buildings 3 The future of bio-technology 3 Introduction History is full of life-changing inventions, the printing press, electricity, the telephone not to mention the foundations of medicine, transportation and computers and the Internet. It is well known that technology, coupled with knowledge and innovation have the potential to alter traditional concepts of the urban community. The cities to benefit from these changes are those with strong appeal for artists, creative individuals and younger educated people. The cities which have this creative skill base will be able to adopt and develop new technology. Historically, Melbourne has a long history as a manufacturing city. However with the rise of China and Asia there has been a steady decline in the manufacturing industry in Victoria. Melbourne has revived itself as a knowledge city with higher education arguably being a key factor in Melbourne’s current and future prosperity (Committee for Melbourne, 2007). Can Melbourne leverage from its historical base in manufacturing and knowledge to be a leader in emerging technology? It is well known that a city which can adopt new technology will excel...

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...Present, Future and Ethics of Nanotechnology Marlon Green Writing 122 Vincent E. Lasnik December 7, 2010 Word count: 1871 The world has embraced nanotechnology with open arms. What once was science fiction, something you watched on Star Trek is now a global reality. Majority of us have not even noticed. Whether you are a CEO of a multibillion dollar die cast company, a heart surgeon, an auto repair shop manager, a drug company representative, or even a house painter. Nanotechnology will impact you. This is not just a new range of technology but a new social force. The family of Nano scale technologies, like numerous other perilous issues of our time, stands at a stage of choices for human ethics. The concept of Nano scale technology begins with the boldly speculative nineteen fifty nine speech “There’s Plenty of Room at the Bottom” by Nobel Prize winning Theoretical physicist Richard Feynman. In the speech he said he was not afraid to consider the question whether ultimately in the great future, we can arrange the atoms the way we want (Feynman, 1959). Scientists in the beginning had meant Nano machines of some sort that would be able to build desired entities atom by atom (Molecular manufacturing). Today nanotechnology can be more broadly viewed as the contemporary result of a natural downsizing progression in nearly all the sciences and there techniques. Nanotechnology is the study and control......

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