Nanonephrology in Veterinary Medicine: A Branch Of Nanomedicine for Renal Diseases in Animals

AL-Hamdany, E. K.; Y. Al-hbiti, Thanoon

doi:10.21608/javs.2020.117996

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	Nanonephrology in Veterinary Medicine: A Branch Of Nanomedicine for Renal Diseases in Animals
Article 3, Volume 5, Issue 4, October 2020, Page 17-24 PDF (965.04 K)
Document Type: Review Article
DOI: 10.21608/javs.2020.117996
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Authors
E. k. AL-Hamdany ¹; Thanoon Y. Al-hbiti²
¹Department of pathology and poultry diseasecollege of veterinary medicine University of Mosul, Mosul, Iraq.
²Department of veterinary pathology and poultry Diseases, college of veterinary medicine, University of Mosul, Mosul, Iraq.
Receive Date: 30 July 2020, Revise Date: 18 August 2020, Accept Date: 24 August 2020
Abstract
Nanotechnology is a fast-growing technology because of It's capable of solving many problems related to animal production and health and plays important roles in the veterinary medicine field. Nanoparticles are characterized by minimal size, it has a role in the improvement of drug delivery, animal health and production. Also used as alternative antimicrobial agents inspect of using large amounts of antibiotics, new drug and vaccine as delivery agents with improved characteristic and performance, diagnostic therapeutic, nutrient delivery, feed additive, biocidal agents and increase the quality of food by using many kinds of nanoparticles such as a polymeric nanoparticle, liposomes, dendrimers and metal nanoparticles. Nanonephrology is a branch of nanomedicine deals with the study of kidney proteins at the nano level and study of cellular structure and process that happened in the kidney with the help of imaging by nano technique and with use of very little size (nano size) particle in treatment of kidney disorder which include acute and chronic kidney disease. With the help of nanotechnology, we replace kidney transplantations and dialysis with low cost and safe animal and human life. Nanonephrology gives us information of molecular structure at the cellular level in normal kidneys functions and at pathological state by studying the chemical and physical characteristic of kidneys proteins and cells at the atomic level by design and structure of nanoparticles that will be matched to the renal cells thus safely and easily perform their function in the kidney. The advantages of nanonephrology in nanomedicine are focused on renal nano diagnostics for studies of basic renal function and early diagnosis of acute and chronic kidney disorders.
Keywords
kidney disease; nanomedicine; nanonephrology; nanoparticles; nanotechnology
Main Subjects
Nanotechnology


References
ALLEN R NISSENSON, CLAUDIO RONCO, GAYLE PERGAMIT, MARTIN EDELSTEIN AND RICHARD WATTS.2005. Continuously functioning artificial nephron system: the promise of nanotechnology. hemodialysis international.9(3):210-217 doi.org/10.1111/j.1492-7535. BENTOLILA LA, EBENSTEIN Y AND WEISS S.2009. Quantum dots for in vivo small-animal imaging. j Nucl med;50:493–496. doi: 10.2967/jnumed.108.053561. BHASKAR S, TIAN F, STOEGER T, KREYLING W, DE LA FUENTE JM, GRAZÚ V, BORM P, ESTRADA G, NTZIACHRISTOS V., RAZANSKY D AND BHASKAR S.2010.Multifunctional nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: perspectives on tracking and neuroimaging. part fibre Toxicol.;7:3.doi: 10.1186/1743-8977-7-3. BOLLO E.2007. Nanotechnologies applied to veterinary diagnostics. Vet. Res. Commun. 31: 145-147. doi: 10.1007/s11259-007-0080-x. BUZEA C, PACHECO BI, ROBBIE K.2007. Nanomaterials and nanoparticles: sources and toxicity. biointerphases.2:1–103. doi: 10.1116/1.2815690. CHAKRAVARTHI. P AND SRI N. BALAJI. 2010.applications of nanotechnology in veterinary medicine vikrama .veterinary world,3(10):477-480. doi: 10.5455/vetworld.2010.477-480. CHEN G, ROY I, YANG C AND PRASAD, P. N. 2016.Nanochemistry and nanomedicine for nanoparticle-based diagnostics and therapy. Chem. Rev. 116: 2826–2885. https://doi.org/10.1021/acs.chemrev.5b00148. CHOI HS, LIU W, MISRA P, TANAKA E, ZIMMER J P AND ITTY B IPE.2007.Renal clearance of quantum dots.Nat Biotechnol.25(10) :1165-1170.http://dx.doi.org/10.1038/nbt1340. DESPINA CHATZIHARALAMBOUS, VASILIKIL YGIROU, AGNIESZKA LATOSINSKA, KONSTANTINOS STRAVODIMOS, ANTONIA VLAHOU, VERA JANKOWSKI, AND JEROME ZOIDAKIS.2016. Analytical Performance of ELISA Assays in Urine: One More Bottleneck towards Biomarker Validation and Clinical Implementation. PLoS One. 2016;11(2): e0149471. doi: 10.1371/ journal. pone.0149471. DILNAWAZ F, SAHOO SK AND DILNAWAZ F.2015. Therapeutic approaches of magnetic nanoparticles for the central nervous system. drug discovery today.20(10):1256-64. doi: 10.1016/j.drudis. 2015.06.008. DING-PING BAI INT, XIN-YU LIN, YI-FAN HUANG AND XI-FENG ZHANG .2018. Theranostics aspects of various nanoparticles in veterinary medicine. Int j mol sci. 24;19(11):3299. doi: 10.3390/ijms19113299. ELGQVIST, J., 2018. Nanoparticles as theranostic vehicles in experimental and clinical applications—focus on prostate and breast cancer. Int j mol sci.18:1102. EL-SAYED A AND KAMEL M.2018.Advanced applications of nanotechnology in veterinary medicine. environ sci pollut res int 27(16):19073-19086. doi: 10.1007/s11356-018-3913-y. ERATHODIYI L N AND YING JY.2011. Functionalization of inorganic nanoparticles for bioimaging applications. acc chem res.44:925–935. https://doi.org/10.1021/ar2000327. FADY SAYED YOUSSEF, HOSSNY AWAD EL-BANNA, HESHAM YOUSSEF ELZORBA, AND AHMED MOHAMED GALAL. 2019. Application of some nanoparticles in the field of veterinary medicine-int j vet sci med7(1): 78–93. doi: 10.1080/23144599.2019.1691379. FAROKHZAD O C AND LANGER R. 2009.Impact of nanotechnology on drug delivery. ACS nano. 3, 16–20 .https://doi.org/10.1021/nn900002m. FATTAL E, YOUSSEF M AND COUVREUR P .1989. Treatment of experimental salmonellosis in mice with ampicillin-bound nanoparticles. Antimicrob agents chemother.33:1540–1543. doi: 10.1128/aac.33.9.1540. FENEQUE, J., 2003. The future of nanopharmaceuticals in veterinary medicine. http://www.nanotech-now.com/jose--feneque/nanopharmaceuticals-and-veterinary-medicine.htm. FISSELL W H, HUMES H D, FLEISCHMAN A H AND ROY S.2007.Dialysis and nanotechnology: now, 10 years, or never? Blood purif.25(1):12-7. doi: 10.1159/000096391. GARABED E KNOYAN .2017.Nephrology: as it was then, but is not Am J Kidney Dis. 69(1):129-135. doi: 10.1053/j.ajkd.2016.06.029. GUERRERO F, CARMONA A, ORTEGA R, CA˜NADILLAS S, CRESPO R, HERRERA C.2017. Relevance of protein content within the renal scaffold for kidney bioengineering and regeneration. J Biomed Sci Eng (JBiSE).10: 509–26.30. HAICK H, HAKIM M, PATRASCU M, LEVENBERG C, SHE HADA N AND NAKHOUL F.2009. Sniffing chronic renal failure in rat model byan array of random networks of single-walled carbon nanotubes. Sniffing chronical renal failure in rat by an array of a random network of SWCNTs. ACS Nano.3: 1258–66.12. HASSANZADEH P, ATYABI F, DINARVAND R AND HASSANZADEH P.2017.Application of modelling and nanotechnology-based approaches: the emergence of breakthroughs in theranostics of central nervous system disorders. life sci.1;182:93-103. doi: 10.1016/j.lfs.2017.06.001. HASSANZADEH P, ATYABI F, DINARVAND R AND HASSANZADEH P.2018. Ignoring the modelling approaches: towards the shadowy paths in nanomedicine. j control release. 28;280:58-75. doi: 10.1016/j.jconrel.2018.04.042. HILL EK, LI J AND HILL EK.2017. Current and future prospects for nanotechnology in animal production. J. Anim. Sci. Biotechnol., 14;8:26. doi: 10.1186/s40104-017-0157-5. HONG YING MAO, SOPHIE LAURENT, WEI CHEN, OMID AKHAVAN, MOHAMMAD IMANI, ALI AKBAR ASHKARRAN AND MORTEZA MAHMOUDI GRAPHENE.2013. Promises, facts, opportunities, and challenges in nanomedicine. chemical reviews .113 (5) , 3407-3424. https://doi.org/10.1021/cr300335p. HOUSHANG AMIRI, KOLSOUM SAEIDI, PARVIN BORHANI, ARASH MANAFIRAD, MAHDI GHAVAMI AND VALERIO ZERBI .2013. Alzheimer’s disease: pathophysiology and applications of magnetic nanoparticles as more theranostic agents. ACS chemical neuroscience 4 (11), 1417-1429. https://doi.org/10.1021/cn4001582. JAIN SK, SAHNI Y AND NEETU R.2011. Nanotoxicology: an emerging discipline. vet world. 4:35–40. https://doi.org/10.5455/vetworld. KAMALY N, HE J C, AUSIELLO A D AND FAROKHZAD O C.2016. Nanomedicines for renal disease: current status and future applications.nat rev Nephrol. 12;738-753.http://dx.doi.org/10.1038/nrneph.2016.156. KIM J S, YOON T J, YU K N, NOH M S AND WOO M.2006. Cellular uptake of magnetic nanoparticle is mediated through energy-dependent endocytosis in a549 cells. j. vet. sci.7: 321-326. doi: 10.4142/jvs.2006.7.4.321 KUKOWSKA-LATALLO J F, CANDIDO K A, CAO Z, NIGAVEKAR S S AND MAJOROS I J.2005. Nanoparticle targeting of anticancer drug improves therapeutic response in animal model of human epithelial cancer. Cancer Res. 65: 5317-5324. doi: 10.1158/0008-5472.can-04-3921. LEE SH, LEE JB, BAE MS, BALIKOV DA, HWANG A, BOIRE TC, KWON IK, SUNG HJ AND YANG JW. 2015.Current progress in nanotechnology applications for diagnosis and treatment of kidney diseases. advanced healthcare materials. 4(13):2037-45 doi10.1002/adhm.201500177. LI H, MU Y, YAN J, CUI D, OU W AND WAN Y.2007. Label-freephotoelectrochemical immunosensor for neutrophil gelatinase-associated lipocalin based on the use of nanobodies. Anal Chem. 87(3):15.11. https://doi.org/10.1021/ac504589d. LIU J,YU M AND ZHOU C .2013.Renal clearable inorganic nanoparticles: a new frontier of bionanotechnology.materialstoday. 16: 477-486. .doi: 10.1016/j.mattod.2013.11.003.Affiliations LONGSON, G.2007. Nanotechnology in veterinary medicine-its potential role in the treatment of feline hyperthyroidism. research paper based on pathology lectures at vet-medlink 2007, pp: 1-17. http://www.medlinkuk.com/_global/downloads/results_2007/longsong.pdf. MAHRUKH S RIZVI AND KIANOUSH B KASHANI .2017. Biomarkers for early detection of acute kidney injury .the journal of applied laboratory medicine. 2( 3): 386–399, https://doi.org/10.1373/jalm.2017.023325. MANUJA A, KUMAR B AND SINGH RK. 2012.Nanotechnology developments: opportunities for animal health and production. nanotechnol dev. 2012;2:4. https://doi.org/10.4081/nd.2012.e4. MCBAIN S C, YIU HHP AND DOBSON J.2008. Magnetic nanoparticles for gene and drug delivery. Int. J. Nanomed. 3: 169-180. doi: 10.2147/ijn.s1608. MEDINA-REYES EI, GARCIA-VIACOBO D, CARRERO-MARTINEZ FA, CHIRINO YI AND MEDINA-REYES EI.2017.Applications and risks of nanomaterials used in regenerative medicine, delivery systems, theranostics, and therapy. Crit Rev. Ther. Drug Carrier Syst. 34(1):35-61. MEENA NS , SAHNI Y, DINESH THAKUR AND RP SINGH.2018. Applications of nanotechnology in veterinary therapeutics journal of entomology and zoology studies.6(2): 167-175. MICHALET X, PINAUD F F AND BENTOLILA L A. 2005. Quantum dots for live cells, in vivo imaging, and diagnostics science 307: 538-544. doi: 10.1126/science.1104274 MIESZAWSKA AJ, MULDER WJ AND FAYAD ZA.2013. Multifunctional gold nanoparticles for diagnosis and therapy of disease. Mol Pharm. 10(3):831–847. doi: 10.1021/mp3005885. MINAKSHI PRASAD, UPENDRA P.LAMBE, BASANTI BRAR,IKBALSHAH,MANIMEGALAIJ,KOUSHLESHRANJAN,REKHARAO,SUNILKUMAR,SHEEFALIMAHANT,SANDIPKUMARKHURANA,HAFIZM.N.IQBAL,KULDEEPDHAMA, JYOTIMISRI AND GAYAPRASAD.2017.Nanotherapeutics: An insight into healthcare and multi-dimensional applications in medical sector of the modern world. https://doi.org/10.1016/j.biopha.2017.11.026. MISHRA B, PATEL BB AND TIWARI S.2010. Colloidal nanocarriers: a review on formulation technology, types and applications toward targeted drug delivery. Nanomedicine. 6(1):9–24. MOHANRAJ VJ, CHEN Y. 2006.Nanoparticles - a review. Trop.J. Pharma. 5:561–573. doi: 10.4314/tjpr.v5i1.14634. MOHANTYA N., PALAIB T., PRUSTYC B.2014. An overview of nanomedicine in veterinary science. Vet Res.2:90–95. MUTHU MS, LEONG DT, MEI L, FENG SS AND MUTHU MS.2014. Nanotheranostics - application and further development of nanomedicine strategies for advanced theranostics. theranostics 26;4(6):660-77. doi: 10.7150/thno.8698. NARDUCCI, D., 2007. An introduction to nanotechnologies: whats in it for us. Vet. Res. Commun 31: 131-137. doi: 10.1007/s11259-007-0082-8. NAZILA KAMALY, JOHN CIJIANG , HEJOHN CIJIANG, HEDENNIS A, AUSIELLODENNIS, A AUSIELLOOMID , AND C FAROKHZAD.2016. Nanomedicines for renal disease: current status and future applications nat rev Nephrol 12, 738–753.https://doi.org/10.1038/nrneph. NUM SM AND USEH NM.2013. Nanotechnology applications in veterinary diagnostics and therapeutics. Sokoto j vet sci.11:10–14. doi: 10.4314/sokjvs.v11i2.2. NURAY GUNDUZ, ELIF ARSLAN, MUSTAFA O GULER AND AYSE B. TEKINAY.2016. Safety of nanomaterials.271-298. https://doi.org/10.1002/9781118987483.ch11. OTTO S WOLFBEIS.2015.An overview of nanoparticles commonly used in fluorescent bioimaging .chemical society reviews. 44(14):4743-68. doi: 10.1039/c4cs00392f. OVIDIU NOVAC AND MARCEL I.2013. Polymeric nanomedicines: polymeric nanomedicines as a treatment of renal diseases. popa. pp. 472-491 (20). doi:10.2174/9781608054848113010016.isbn: 978-1-60805-628-6. PAPIA BASUTHAKUR., SHAGUFTA HAQUE., BROTI ADHIKARY AND CHITTA RANJAN PATRA.2020. Nanomedicine for ischemic diseases: recent development and future challenges. 333-373. https://doi.org/10.1007/978-3-030-41464-1_15. PATIL S, KORE K ANDKUMAR P.2009. Nanotechnology and its applications in veterinary and animal science. Vet World. 2009;2:475–477. doi: 10.5455/vetworld.2009.475-477. PAWAR K AND KAUL G.2012. Toxicity of titanium oxide nanoparticles causes functionality and DNA damage in buffalo (Bubalus bubalis) sperm in vitro. Toxicol Ind Health. 30(6):520-33. doi:10.177/0748233712462475. PEER D., 2007. Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol. 2: 751–760. doi: 10.1038/nnano.2007.387. PISIGNANO D.2007. Nanotechnology and nephrology. G Ital. Nefrol;40:80-6. RAHIMNEJAD M, JAHANSHAHI M AND NAJAFPOUR G.D .2006. Production of biological nanoparticles from bovine serum albumin for drug delivery. Afr. j. Biotechnol .5: 1918-1923. https://doi.org/10.1016/j.ijbiomac.2018.04.043. RAI M, YADAV A AND GADE A.2009. Silver nanoparticles as a new generation of antimicrobials. Biotechnol. adv 27: 76-83. doi: 10.17516/1997-1389-0301. RAJENDRAN D, KUMARG, RAMAKRISHNANS AND SHIBITK.2013.Enhancing the milk production and immunity in Holstein Friesian crossbred cow by supplementing novel nano zinc oxide. Research journal of biotechnology .8 (5), 11-17 21. RAJENDRAN D.2013. Application of nano minerals in animal production system. Res J. Biotechnol. 8(3):1. RAJIV SAINI, SANTOSH SAINI AND SUGANDHA R SAINI.2012. Nanotechnology in nephrology .saudi journal of kidney diseases and transplantation .23: 2; 367. REDDY L H AND COUVREUR P.2011. Nano technology for therapy and imaging of liver diseases. j. Hematol. 55(6):1461-6. doi: 10.1016/j. jhep.2011.05.039. RILEY MK AND VERMERRIS W.2017. Recent advances in nanomaterials for gene delivery a review. Nanomaterials .7:94. 7(5):94. doi: 10.3390/nano7050094. RIZZO LY, THEEK B AND STORM G.2013. Recent progress in nanomedicine: therapeutic, diagnostic and theranostic applications. Curr Opin bio technol.24:1159–1166. 24(6):1159-66. doi: 10.1016/j.copbio.2013.02.020. RYAN M WILLIAMS, EDGAR A JAIMES AND DANIEL A HELLER.2016. Nanomedicines for kidney diseases .kidney international 90(4):740–745. doi.org/10.1016/j.kint.2016.03.041. SAHA K, BAJAJ A, DUNCAN B AND ROTELLO V M. 2011. Beauty is skin deep: a surface monolayer perspective on nanoparticle interactions with cells and bio-macromolecules.small.7(14): 1903–1918. doi: 10.1002/smll.201100478 SAINI R, SAINI S AND SHARMA S.2010. Nanotechnology: the future medicine J Cutan Aesthet. Surg .3(1):32-33. doi: 10.4103/0974-2077.63301. SARKER NC, KEOMANIVONG F, BORHAN M, RAHMAN S, SWANSON K AND SARKER NC.2018. In vitro evaluation of nano zinc oxide (nzno) on mitigation of gaseous emissions. J. Anim. Sci. Technol. 2018 nov 9;60:27. doi: 10.1186/s40781-018-0185-5. SCOTT N R. 2005. Nanotechnology and animal health. Rev. sci. Tech. Off. int. epiz. 24 (1), 425-432. doi: 10.20506/rst.24.1.1579. SEREEMASPUN A, HONGPITICHAROEN P, ROJANATHANES R, MANEEW ATTANAPINYO P, EKGASIT S AND WARISNOICHAROEN W.2008. Inhibition of human cytochrome p450 enzymes by metallic nanoparticles: a preliminary to nanogenomics. int. j. pharmacol., 4: 492-495doi: 10.3923/ijp.2008.492.495. SINGH M, S MANIKANDAN AND A K KUMARAGURU.2011. Nanoparticles: a new technology with wide applications. Res. J. Nanosci. Nanotechnol 1: 1-11. doi: 10.3923/rjnn.2011.1.11. SINGH SEKHON . 2012. Nanoprobes and their applications in veterinary medicine and animal health. research journal of nanoscience and nanotechnology, 2: 1-16. doi: 10.3923/rjnn.2012.1.16. SIRIRAT N, LU JJ AND HUNG ATY.2013. Effect of different levels of nanoparticles chromium picolinate supplementation on performance, egg quality, mineral retention, and tissues minerals accumulation in layer chickens. j agric sci.5(2):150–159. doi:10.5539/jas.v5n2p150. SORIANO ML, RODRÍGUEZ-BENOT A AND VALCÁRCEL M.2018. Nanotechnological foundations of a “new” nephrology.nefrologiajul 38(4):368-378. doi: 10.1016/j.nefro.2018.02.007. SWAIN PS, RAJENDRAN D AND RAO SB. 2015.Preparation and effects of nano mineral particle feeding in livestock: a review. Vet World. 8(7):888–891. doi: 10.14202/vetworld.2015.888-891. TANG W , FAN W , LAU J , DENG L , SHEN Z , CHEN X AND TANG W .2019. Emerging blood-brain-barrier-crossing nanotechnology for brain cancer theranostics. chem soc rev. 4;48(11):2967-3014. doi: 10.1039/c8cs00805a. TASSEW BELETE BAHRU AND EYASU GEBRIE AJEBE.2019. A review on nanotechnology: analytical techniques use and applications. irjpac.19(4):1-10 doi https://doi.org/10.9734/irjpac/2019/v19i430117. THOMSEN LB, LINEMANN T, PONDMAN KM, LICHOTA J, KIMKS, PIETERS RJ, VISSER GM AND MOOS T. 2013.Uptake and transport of superparamagnetic iron oxide nanoparticles through human brain capillary endothelial cells. ACS chemical neuroscience 4 (10), 1352-1360. https://doi.org/10.1021/cn400093z THULASI A, RAJENDR AN D.JASH S. 2013. Nanobiotechnology in animal nutrition. Vol. 17. new Delhi: Satish serial publishing house: pp 499-515. TORRESSANGIAO E, HOLBAN AM AND GESTAL MC. 2016.Advanced nanobiomaterials: vaccines, diagnosis and treatment of infectious diseases. molecules. 21:867. doi: 10.3390/molecules21070867. UNDERWOOD C AND VAN EPS AW.2012. .Nanomedicine and veterinary science: the reality and the practicality. Vet j. 193(1):12-23. doi: 10.1016/j.tvjl.2012.01.002. VAIDYA V S, FERGUSON M A AND BONVENTRE J V.2010.Biomarkers of acute kidney injury.rev pharm Toxicol. 48:463-493. WANG J, BYRNE J D, NAPIER M E AND DESIMONE J M.2011.More effective nanomedicines through particle design. small 7(14):1919-31. doi: 10.1002/smll.201100442. WILLIAMS R M, JAIMESE A AND HELLER D A.2016.Nanomedicines for kidney diseases.kidney int. 90: 740-745.http://dx.doi.org/10.1016/j.kint. 2016.03.041. WILLIAMS R, M SHAH J AND NG BD .2015.Mesoscale nanoparticles selectively target the renal proximal tubule epithelium. Nano Lett. 15: 2358-2364. doi: 10.1021/nl504610d. epub 2015. WU T-J, CHIU H-Y AND YU J.2018. Nanotechnologies for early diagnosis, in situ disease monitoring, and prevention. In: uskoković v, uskoković dp, editors. Nanotechnologies in preventive and regenerative medicine. Chapter 1. Amsterdam: elsevier.p. 1–92. XU J, PENG C, YO M AND ZHENG J.2017.Renal clearable noble metals nanoparticles: photoluminescence, elimination and biomedical applications.Wiley internship Rev Nanomed nanobiotechnol.9(5) ; e1453. doi: 10.1002/wnan.1453. YU L., SCHERLAG BJ, DORMERK, NGUYENT K, POPEC , FUNG KM AND PO S S. 2010. Autonomic denervation with magnetic nanoparticles. Circulation. 122: 2653-2659.https://doi.org/10.1161/ circulationaha.110.940288 ZADEH, J.B. AND MORADI-KOR, N.2013 . Nano-technology applications in veterinary science. Onl. J. Vet. Res. 17:419–425. ZHA LY, ZR XU, M Q WANG AND L Y GU.2007. Effects of chromium nanoparticle dosage on growth, body composition, serum hormones and tissue chromium in Sprague-Dawley rats. j. Zhejiang Univ. Sci. b. 8: 323-330. ZHANG L AND WEBSTER TJ.2009. Nanotechnology and nanomaterials: promises for improved tissue regeneration. Nanotoday.4:66–80.33.
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