Nanotechnology for tissue engineering: Need, techniques and applications

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Abstract
Tissue engineering is very fast growing scientific area in this era which is 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 it helps to produce materials 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 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.

Keywords
Bio-scaffold; Electrospinning; Grafting; Nanobiotechnology; Tissue engineering

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Nanotechnology for tissue engineering: Need, techniques and applications

  1. 1. This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier’s archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/authorsrights
  2. 2. Author's personal copy 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 a r t i c l e i n f o Article history: Received 1 December 2012 Accepted 27 February 2013 Available online 17 March 2013 Keywords: Bio-scaffold Electrospinning Grafting Nanobiotechnology Tissue engineering a b s t r a c t Tissue engineering is very fast growing scientific area in this era which is 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 it helps to produce materials 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 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. Introduction 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 tech- nology” been developed for more accuracy on positioning and viability, complexity, interaction etc., using micro and nano- technology 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: shivenduranjan@gmail.com (S. Ranjan). Available online at www.sciencedirect.com journal homepage: www.elsevier.com/locate/jopr 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 7 ( 2 0 1 3 ) 2 0 0 e2 0 4 0974-6943/$ e see front matter Copyright ª 2013, JPR Solutions; Published by Reed Elsevier India Pvt. Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jopr.2013.02.021
  3. 3. Author's personal copy 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 controlled- release nanoparticles with applications in tissue engineer- ing, for mimicking native tissues since biomaterials to be engineered is of nanometre size like extracellular fluids, bone marrow, cardiac tissues etc.5 2.1. 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 2.2. Nanotextured substrates for tissue engineering 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 in- creases when poly(lactic-co-glycolide) nanosurface is treated with NaOH.10 E-beam lithography is useful in nano tissue en- gineering.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 2.3. Self-assembled nanomaterials Methods for inducing self assembly in tissue engineering are biomimetic coating, electrolytic deposition (ELD) and pH in- duction 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 hydro- phobic 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. 1 e Schematic representation of benefits of using micro and nanofabrication for tissue engineering. Fig. 2 e Size scale of various biological structures. 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 7 ( 2 0 1 3 ) 2 0 0 e2 0 4 201
  4. 4. Author's personal copy attachment, which could be overcome by branched PA asso- ciated 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 3. Applications From the above discussion we can conclude that tissue engi- neering 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. 3.1. 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, align- ment, 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 uni- form shape and it also have affects the rate of lipid production and thus differentiation of cells to adipocytes.23 3.2. Neural cells tissue engineering through micro and nanotechnology Techniques used are as: (i) Electrospinning helps in cell dif- ferentiation, 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 pro- tocol 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 3.3. 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. 3 e Basic series of events during tissue engineering and implantation. 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). 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 7 ( 2 0 1 3 ) 2 0 0 e2 0 4202
  5. 5. Author's personal copy were cultured on micropatterned agarose gel which acts as biomomicked scaffolds and helps in maintaining chondro- genic phenotype28 (ii) Replica moulding helps to maintain controlled microenvironment and is integrated with inverted microscope to monitor real-time for cell size change in artic- ular chondrocyte.29 3.4. 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 osteopro- genitor cells are cultured on collagen and thus appropriate surface topography enhances bone formation.30 (ii) Photoli- thography is providing better groove topography for primary human osteoblasts and helps in cellular adhesion and osteo- specific function and in determining cellular response also used in “patterned cell cocultures” for Human osteogenic sarcoma cells on Photocrosslinkable chitosan by using lyso- zyme.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 3.5. 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 attach- ment and migration of cells along the axis in human coronary artery smooth muscle cell culture with poly(L-lactid-co- ε-caprolactone).6 3.6. 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-co- ethyl 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 poly- dimethylsiloxane 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. r e f e r e n c e s 1. Khetani SR, Bhatia SN. Engineering tissues for in vitro applications. Curr Opin Biotechnol. 2006;17(5):524e531. 2. Rivron NC, Liu J, Rouwkema J, de Boer J, van Blitterswijk CA. Engineering vascularised tissues in vitro. Eur Cell Mater. 2008;15:27e40. 3. Ryu W, Fasching RJ, Vyakarnam M, et al. Microfabrication technology of biodegradable polymers for interconnecting microstructures. J Microelectromech Syst. 2006;15(6):1457e1465. 4. Nakanishi J, Takarada T, Yamaguchi K, et al. Recent advances in cell micropatterning techniques for bioanalytical and biomedical sciences. Anal Sci. 2008;24(1):67e72. 5. Chung Bong Geun, Kang Lifeng, Khademhosseini Ali. Micro-and nanoscale technologies for tissue engineering and drug discovery applications. Expert Opin Drug Discov. 2007;2(12):1e16. 6. Cy Xu, Inai R, Kotaki M, Ramakrishna S. Aligned biodegradable nanofibrous structure: a potential scaffold for blood vessel engineering. Biomaterials. 2004;25(5):877e886. 7. Yang F, Murugan R, Wang S, Ramakrishna S. Electrospinning of nano/micro scale poly( L -lactic acid) aligned fibers and their potential in neural tissue engineering. Biomaterials. 2005;26(15):2603e2610. 8. Ma Z, Kotaki M, Inai R, Ramakrishna S. Potential of nanofiber matrix as tissue-engineering scaffolds. Tissue En. 2005;11(12):101e109. 9. Flemming RG, Murphy CJ, Abrams GA, Goodman SL, Nealey PF. Effects of synthetic micro and nano-structured surfaces on cell behaviour. Biomaterials. 1999;20(6):573e588. 10. Miller DC, Thapa A, Haberstroh KM, Webster TJ. Endothelial and vascular smooth muscle cell function on poly (lactic- co -glycolic acid) with nano-structured surface features. Biomaterials. 2004;25(1):53e61. 11. Dalby MJ, Marshall GE, Johnstone HJ, Affrossman S, Riehle MO. Interactions of human blood and tissue cell types with 95-nm-high nanotopography. IEEE Trans Nanobioscience. 2002;1(1):18e23. 12. Schindler M, Ahmed I, Kamal J, et al. 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  6. 6. Author's personal copy 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. 2005;76(3):503e511. 18. Chua K-N, Chai C, Lee P-C, et al. Surface-aminated electrospun nanofibers enhance adhesion and expansion of human umbilical cord blood hematopoietic stem/progenitor cells. Biomaterials. 2006;27(36):6043e6051. 19. Ma K, Chan CK, Liao S, et al. Electrospun nanofiber scaffolds for rapid and rich capture of bone marrow-derived hematopoietic stem cells. Biomaterials. 2008;29(13):2096e2103. 20. Yu BY, Chou PH, Sun YM, et al. Topological micropatterned membranes and its effect on the morphology and growth of human mesenchymal stem cells (hMSCs). J Memb Sci. 2006;273(1e2):31e37. 21. Karp JM, Yeh J, Eng G, et al. Controlling size, shape and homogeneity of embryoid bodies using poly(ethylene glycol) microwells. Lab Chip. 2007;7:786e794. 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. 2007;27(36):5968e5977. 23. Chaubey A, Ross KJ, Leadbetter RM, et al. Surface patterning: tool to modulate stem cell differentiation in an adipose system. J Biomed Mater Res Part B Appl Biomater. 2008;84B(1):70e78. 24. Xie J, Willerth SM, Li X, et al. The differentiation of embryonic stem cells seeded on electrospun nanofibers into neural lineages. Biomaterials. 2008;30:354e362. 25. Bettinger CJ, Orrick B, Misra A, et al. Microfabrication of poly glycerolesebacate) for contact guidance applications. Biomaterials. 2006;27:2558e2565. 26. Vogt AK, Wrobel G, Meyer W, et al. Synaptic plasticity in micropatterned neuronal networks. Biomaterials. 2005;26(15):2549e2557. 27. Schwartz MA, DeSimone DW. Cell adhesion receptors in mechanotransduction. Curr Opin Cell Biol. 2008;20(5):551e556. 28. Petersen EF, Spencer RGS, McFarland EW. Microengineering neocartilage scaffolds. Biotechnol Bioeng. 2002;78(7):801e804. 29. Chao PG, Tang ZL, Angelini E, et al. Dynamic osmotic loading of chondrocytes using a novel microfluidic device. J Biomech. 2005;38(6):1273e1281. 30. Ber S, Torun Ko¨se G, Hasirci V. Bone tissue engineering on patterned collagen films: an in vitro study. Biomaterials. 2005;26(14):1977e1986. 31. Karp JM, Yeo Y, Geng WL, et al. A photolithographic method to create cellular micropatterns. Biomaterials. 2006;27(27):4755e4764. 32. Kenar H, Kocabas A, Aydinli A, et al. Chemical and topographical modification of PHBV surface to promote osteoblast alignment and confinement. J Biomed Mater Res Part A. 2008;85A(4):1001e1010. 33. Tuzlakoglu K, Bolgen N, Salgado AJ, et al. Nano- and micro-fiber combined scaffolds: a new architecture for bone tissue engineering. J Mater Sci Mater Med. 2005;16(12):1099e1104. 34. Kurpinski K, Chu J, Hashi C, et al. Anisotropic mechanosensing by mesenchymal stem cells. Proc Natl Acad Sci U S A. 2006;103(44):16095e16100. 35. Daxini SC, Nichol JW, Sieminski AL, et al. Micropatterned polymer surfaces improve retention of endothelial cells exposed to flow-induced shear stress. Biorheology. 2006;43(1):45e55. 36. Khademhosseini A, Eng G, Yeh J, et al. Microfluidic patterning for fabrication of contractile cardiac organoids. Biomed Microdevices. 2007;9(2):149e157. 37. Khademhosseini A, Jason Burdick A, Langer R. Fabrication of gradient hydrogels using a microfluidics/photopolymerization process. Langmuir. 2004;20(13):5153e5156. 38. Lin X, Helmke BP. Micropatterned structural control suppresses mechanotaxis of endothelial cells. Biophys J. 2008;95(6):3066e3078. 39. Carraro A, Hsu WM, Kulig KM, et al. In vitro analysis of a hepatic device with intrinsic microvascular-based channels. Biomed Microdevices. 2008;10(6):795e805. 40. Tsang VL, Chen AA, Cho LM, et al. Fabrication of 3D hepatic tissues by additive photopatterning of cellular hydrogels. FASEB J. 2007;21(3):790e801. 41. Khetani SR, Bhatia SN. Microscale culture of human liver cells for drug development. Nat Biotechnol. 2008;26:120e126. 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 7 ( 2 0 1 3 ) 2 0 0 e2 0 4204

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