Sciatic nerve regeneration by transplantation of Schwann cells via erythropoietin controlled-releasing polylactic acid/multiwalled carbon nanotubes/gelatin nanofibrils neural guidance conduit
Majid Salehi
Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 1417755469 Iran
Search for more papers by this authorMahdi Naseri-Nosar
Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 1417755469 Iran
Search for more papers by this authorSomayeh Ebrahimi-Barough
Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 1417755469 Iran
Search for more papers by this authorMohammdreza Nourani
Nano Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, 1435944711 Iran
Search for more papers by this authorArash Khojasteh
Department of Tissue Engineering, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Search for more papers by this authorAmir-Ali Hamidieh
Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, 1411713135 Iran
Search for more papers by this authorAmir Amani
Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 1417755469 Iran
Search for more papers by this authorSaeed Farzamfar
Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 1417755469 Iran
Search for more papers by this authorCorresponding Author
Jafar Ai
Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 1417755469 Iran
Correspondence to: J. Ai; e-mail: [email protected]Search for more papers by this authorMajid Salehi
Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 1417755469 Iran
Search for more papers by this authorMahdi Naseri-Nosar
Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 1417755469 Iran
Search for more papers by this authorSomayeh Ebrahimi-Barough
Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 1417755469 Iran
Search for more papers by this authorMohammdreza Nourani
Nano Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, 1435944711 Iran
Search for more papers by this authorArash Khojasteh
Department of Tissue Engineering, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Search for more papers by this authorAmir-Ali Hamidieh
Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, 1411713135 Iran
Search for more papers by this authorAmir Amani
Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 1417755469 Iran
Search for more papers by this authorSaeed Farzamfar
Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 1417755469 Iran
Search for more papers by this authorCorresponding Author
Jafar Ai
Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 1417755469 Iran
Correspondence to: J. Ai; e-mail: [email protected]Search for more papers by this authorThis article was published online on 04 July 2017. An error was subsequently identified. This notice is included in the online and print versions to indicate that both have been corrected 21 July 2017.
Abstract
The current study aimed to enhance the efficacy of peripheral nerve regeneration using an electrically conductive biodegradable porous neural guidance conduit for transplantation of allogeneic Schwann cells (SCs). The conduit was produced from polylactic acid (PLA), multiwalled carbon nanotubes (MWCNTs), and gelatin nanofibrils (GNFs) coated with the recombinant human erythropoietin-loaded chitosan nanoparticles (rhEpo-CNPs). The PLA/MWCNTs/GNFs/rhEpo-CNPs conduit had the porosity of 85.78 ± 0.70%, the contact angle of 77.65 ± 1.91° and the ultimate tensile strength and compressive modulus of 5.51 ± 0.13 MPa and 2.66 ± 0.34 MPa, respectively. The conduit showed the electrical conductivity of 0.32 S cm−1 and lost about 11% of its weight after 60 days in normal saline. The produced conduit was able to release the rhEpo for at least 2 weeks and exhibited favorable cytocompatibility towards SCs. For functional analysis, the conduit was seeded with 1.5 × 104 SCs and implanted into a 10 mm sciatic nerve defect of Wistar rat. After 14 weeks, the results of sciatic functional index, hot plate latency, compound muscle action potential amplitude, weight-loss percentage of wet gastrocnemius muscle and Histopathological examination using hematoxylin-eosin and Luxol fast blue staining demonstrated that the produced conduit had comparable nerve regeneration to the autograft, as the gold standard to bridge the nerve gaps. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1463–1476, 2018.
REFERENCES
- 1Burnett MG, Zager EL. Pathophysiology of peripheral nerve injury: A brief review. Neurosurg Focus 2004; 16: 1–7.
- 2Klein S, Vykoukal J, Felthaus O, Dienstknecht T, Prantl L. Collagen Type I Conduits for the Regeneration of Nerve Defects. Materials. 2016; 9: 219.
10.3390/ma9040219 Google Scholar
- 3Li B-B, Yin Y-X, Yan Q-J, Wang X-Y, Li S-P. A novel bioactive nerve conduit for the repair of peripheral nerve injury. Neural Regen Res 2016; 11: 150.
- 4Goulart CO, Martinez AMB. Tubular conduits, cell-based therapy and exercise to improve peripheral nerve regeneration. Neural Regen Res 2015; 10, 565.
- 5Daly W, Yao L, Zeugolis D, Windebank A, Pandit A. A biomaterials approach to peripheral nerve regeneration: Bridging the peripheral nerve gap and enhancing functional recovery. J R Soc Interface 2012; 9: 202–221.
- 6Yucel D, Kose GT, Hasirci V. Polyester based nerve guidance conduit design. Biomaterials 2010; 31: 1596–1603.
- 7Kehoe S, Zhang X, Boyd D. FDA approved guidance conduits and wraps for peripheral nerve injury: a review of materials and efficacy. Injury 2012; 43: 553–572.
- 8Chiono V, Tonda-Turo C, Trends in the design of nerve guidance channels in peripheral nerve tissue engineering. Prog Neurobiol. 2015; 131: 87–104.
- 9Auras RA, Lim L-T, Selke SE, Tsuji H. Poly(Lactic Acid): Synthesis, Structures, Properties, Processing, and Applications, Vol. 10. United States: John Wiley & Sons; 2011.
- 10Shalumon K, Deepthi S, Anupama M, Nair S, Jayakumar R, Chennazhi K. Fabrication of poly(l-lactic acid)/gelatin composite tubular scaffolds for vascular tissue engineering. Int J Biol Macromol 201; 72: 1048–1055.
- 11Hoque ME, Nuge T, Yeow TK, Nordin N, Prasad R. Gelatin based scaffolds for tissue engineering-A review. Polym Res J, 2015; 9: 15.
- 12Lu W, Ma M, Xu H, Zhang B, Cao X, Guo Y. Gelatin nanofibers prepared by spiral-electrospinning and cross-linked by vapor and liquid-phase glutaraldehyde, Mater Lett 2015; 140: 1–4.
- 13Zhang Z, Rouabhia M, Wang Z, Roberge C, Shi G, Roche P, Li J, Dao LH. Electrically conductive biodegradable polymer composite for nerve regeneration: Electricity-stimulated neurite outgrowth and axon regeneration. Artif Organs 2007; 31: 13–22.
- 14Arslantunali D, Budak G, Hasirci V. Multiwalled CNT-pHEMA composite conduit for peripheral nerve repair. J Biomed Mater Res A 2014; 102: 828–841.
- 15Gupta P, Sharan S, Roy P, Lahiri D. Aligned carbon nanotube reinforced polymeric scaffolds with electrical cues for neural tissue regeneration. Carbon 2015; 95: 715–724.
- 16Bosi S, Fabbro A, Cantarutti C, Mihajlovic M, Ballerini L, Prato M. Carbon based substrates for interfacing neurons: Comparing pristine with functionalized carbon nanotubes effects on cultured neuronal networks. Carbon 2016; 97: 87–91.
- 17Lovat V, Pantarotto D, Lagostena L, Cacciari B, Grandolfo M, Righi M, Spalluto G, Prato M, Ballerini L. Carbon nanotube substrates boost neuronal electrical signaling. Nano Lett 2005; 5: 1107–1110.
- 18Belkas JS, Shoichet MS, Midha R. Peripheral nerve regeneration through guidance tubes. Neurol Res 2004; 26: 151–160
- 19Webber C, Zochodne D. The nerve regenerative microenvironment: Early behavior and partnership of axons and Schwann cells. Exp Neurol 2010; 223: 51–59.
- 20Li X, Gonias SL, Campana WM. Schwann cells express erythropoietin receptor and represent a major target for Epo in peripheral nerve injury. Glia 2005; 51: 254–265.
- 21Yin Z-S, Zhang H, Gao W. Erythropoietin promotes functional recovery and enhances nerve regeneration after peripheral nerve injury in rats. Am J Neuroradiol 2010; 31: 509–515.
- 22Lykissas MG, Korompilias AV, Vekris MD, Mitsionis GI, Sakellariou E, Beris AE. The role of erythropoietin in central and peripheral nerve injury. Clin Neurol Neurosurg 2007; 109: 639–644.
- 23Bokharaei M, Margaritis A, Xenocostas A, Freeman DJ. Erythropoietin encapsulation in chitosan nanoparticles and kinetics of drug release. Curr Drug Deliv 2011; 8: 164–171.
- 24Agnihotri SA, Mallikarjuna NN, Aminabhavi TM. Recent advances on chitosan-based micro-and nanoparticles in drug delivery. J Controlled Release 2004; 100: 5–28.
- 25Cho Y, Shi R, Borgens RB. Chitosan produces potent neuroprotection and physiological recovery following traumatic spinal cord injury. J Exp Biol 2010; 213: 1513–1520.
- 26Wang Y, Zhao Y, Sun C, Hu W, Zhao J, Li G, Zhang L, Liu M, Liu Y, Ding F. Chitosan degradation products promote nerve regeneration by stimulating schwann cell proliferation via miR-27a/FOXO1 axis. Mol Neurobiol 2016; 53: 28–39.
- 27Koshio A, Yudasaka M, Zhang M, Iijima S. A simple way to chemically react single-wall carbon nanotubes with organic materials using ultrasonication. Nano Lett 2001; 1: 361–363.
- 28Hu Y, Jiang X, Ding Y, Zhang L, Yang C, Zhang J, Chen J, Yang Y. Preparation and drug release behaviors of nimodipine-loaded poly(caprolactone)–poly(ethylene oxide)–polylactide amphiphilic copolymer nanoparticles. Biomaterials 2003; 24: 2395–2404.
- 29Namazi H, Rakhshaei R, Hamishehkar H, Kafil HS. Antibiotic loaded carboxymethylcellulose/MCM-41 nanocomposite hydrogel films as potential wound dressing. Int J Biol Macromol 2016; 85: 327–334.
- 30Salehi M, Naseri-Nosar M, Amani A, Azami M, Tavakol S, Ghanbari, H. Preparation of pure PLLA, pure chitosan, and PLLA/chitosan blend porous tissue engineering scaffolds by thermally induced phase separation method and evaluation of the corresponding mechanical and biological properties. Int J Polym Mater Polym Biomater 2015; 64: 675–682.
- 31Salehi M, Farzamfar S, Bastami F, Tajerian, R. Fabrication and characterization of electrospun PLLA/collagen nanofibrous scaffold coated with chitosan to sustain release of aloe vera gel for skin tissue engineering. Biomed Eng 2016; 28: 1650035.
- 32Terraf P, Ai J, Kouhsari S, Babaloo H. Indirect co-culture with schwann cells as a new approach for human endometrial stem cells neural transdifferentiation. Int J Stem Cell Res Transplant 2016; 4: 235–242.
- 33Dijkstra JR, Meek MF, Robinson PH, Gramsbergen A. Methods to evaluate functional nerve recovery in adult rats: Walking track analysis, video analysis and the withdrawal reflex. J Neurosci Methods 2000; 96: 89–96.
- 34Naseri-Nosar M, Salehi M, Hojjati-Emami S. Cellulose acetate/poly lactic acid coaxial wet-electrospun scaffold containing citalopram-loaded gelatin nanocarriers for neural tissue engineering applications. Int J Biol Macromol 2017; 103: 701–708.
- 35Bulmer C, Margaritis A, Xenocostas A. Production and characterization of novel chitosan nanoparticles for controlled release of rHu-erythropoietin. Biochem Eng J 2012; 68: 61–69.
- 36Chen J, Chu B, Hsiao BS. Mineralization of hydroxyapatite in electrospun nanofibrous poly(L-lactic acid) scaffolds. J Biomed Mater Res A 2006; 79: 307–317.
- 37Lewis S, Lewis A, Lewis P. Prediction of glycoprotein secondary structure using ATR-FTIR. Vib Spectrosc 2013; 69: 21–29.
10.1016/j.vibspec.2013.09.001 Google Scholar
- 38Walsh G. Biopharmaceuticals: Biochemistry and Biotechnology. United States: John Wiley & Sons; 2013.
- 39Benita S. Microencapsulation: Methods and Industrial Applications. United States: CRC Press; 2005.
10.1201/9781420027990 Google Scholar
- 40Siepmann J, Peppas N. Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). Adv Drug Deliv Rev 2001; 48: 139–157.
- 41Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm 1983; 15: 25–35.
- 42Li B, Yoshii T, Hafeman AE, Nyman JS, Wenke JC, Guelcher SA. The effects of rhBMP-2 released from biodegradable polyurethane/microsphere composite scaffolds on new bone formation in rat femora. Biomaterials 2009; 30: 6768–6779.
- 43Naseri-Nosar M, Salehi M, Ghorbani S, Beiranvand SP, Goodarzi A, Azami M. Characterization of wet-electrospun cellulose acetate based 3-dimensional scaffolds for skin tissue engineering applications: Influence of cellulose acetate concentration. Cellulose 2016; 23: 3239–3248.
- 44Salehi M, Naseri-Nosar M, Azami M, Nodooshan SJ, Arish J. Comparative study of poly(L-lactic acid) scaffolds coated with chitosan nanoparticles prepared via ultrasonication and ionic gelation techniques. Tissue Eng Regen Med 2016; 13: 498–506.
10.1007/s13770-016-9083-4 Google Scholar
- 45Zhu X, Cui W, Li X, Jin Y. Electrospun fibrous mats with high porosity as potential scaffolds for skin tissue engineering. Biomacromolecules 2008; 9: 1795–1801.
- 46Amaral I, Granja P, Barbosa M. Chemical modification of chitosan by phosphorylation: An XPS, FT-IR and SEM study. J Biomater Sci Polym Ed 2005; 16: 1575–1593.
- 47Gristina AG, Naylor PT, Myrvik QN. Biomaterial-centered infections: microbial adhesion versus tissue integration. In: Pathogenesis of Wound and Biomaterial-Associated Infections. England: Springer; 1990. pp 193–216.
- 48Kanagaraj S, Varanda FR, Zhil'tsova TV, Oliveira MS, Simões JA. Mechanical properties of high density polyethylene/carbon nanotube composites. Compos Sci Technol 2007; 67: 3071–3077.
- 49Spitalsky Z, Tasis D, Papagelis K, Galiotis C. Carbon nanotube–polymer composites: Chemistry, processing, mechanical and electrical properties. Prog Polym Sci 2010; 35: 357–401.
- 50Wang S, Yaszemski MJ, Knight AM, Gruetzmacher JA, Windebank AJ, Lu L. Photo-crosslinked poly (ɛ-caprolactone fumarate) networks for guided peripheral nerve regeneration: Material properties and preliminary biological evaluations. Acta Biomater 2009; 5: 1531–1542.
- 51Zhang D, Kandadai MA, Cech J, Roth S, Curran SA. Poly (L-lactide)(PLLA)/multiwalled carbon nanotube (MWCNT) composite: Characterization and biocompatibility evaluation. J Phys Chem B 2006; 110: 12910–12915.
- 52Kabiri M, Oraee-Yazdani S, Shafiee A, Hanaee-Ahvaz H, Dodel M, Vaseei M, Soleimani M. Neuroregenerative effects of olfactory ensheathing cells transplanted in a multi-layered conductive nanofibrous conduit in peripheral nerve repair in rats. J Biomed Sci 2015; 22: 1.
- 53Wilson D, Jagadeesh P. Experimental regeneration in peripheral nerves and the spinal cord in laboratory animals exposed to a pulsed electromagnetic field. Spinal Cord 1976; 14: 12–20.
- 54Luo L, Gan L, Liu Y, Tian W, Tong Z, Wang X, Huselstein C, Chen Y. Construction of nerve guide conduits from cellulose/soy protein composite membranes combined with Schwann cells and pyrroloquinoline quinone for the repair of peripheral nerve defect. Biochem Biophys Res Commun 2015; 457: 507–513.
- 55Schnell E, Klinkhammer K, Balzer S, Brook G, Klee D, Dalton P, Mey J. Guidance of glial cell migration and axonal growth on electrospun nanofibers of poly-ɛ-caprolactone and a collagen/poly-ɛ-caprolactone blend. Biomaterials 2007; 28: 3012–3025.
- 56Sirén A-L, Fratelli M, Brines M, Goemans C, Casagrande S, Lewczuk P, Keenan S, Gleiter C, Pasquali C, Capobianco A. Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress. Proc Natl Acad Sci USA 2001; 98: 4044–4049.
- 57Ghezzi P, Brines, M. Erythropoietin as an antiapoptotic, tissue-protective cytokine. Cell Death Differ 2004; 11: S37–S44.
- 58Gassmann M Heinicke K Soliz J Ogunshola OO. Non-Erythroid Functions of Erythropoietin. In: Hypoxia: Through the Lifecycle. United States: Springer; 2003. p. 323–30.
- 59Digicaylioglu M, Lipton SA. Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-κB signalling cascades. Nature 2001; 412: 641–647.
- 60Ma C, Cheng F, Wang X, Zhai C, Yue W, Lian Y, Wang Q. Erythropoietin pathway: A potential target for the treatment of depression. Int J Mol Sci 2016; 17: 677.
- 61Singh S, Wu BM, Dunn JC. The enhancement of VEGF-mediated angiogenesis by polycaprolactone scaffolds with surface cross-linked heparin. Biomaterials 2011; 32: 2059–2069.
- 62Hutton DL, Grayson WL. Stem cell-based approaches to engineering vascularized bone. Curr Opin Chem Eng 2014; 3: 75–82.
- 63Zhang W, Wray LS, Rnjak-Kovacina J, Xu L, Zou D, Wang S, Zhang M, Dong J, Li G, Kaplan DL. Vascularization of hollow channel-modified porous silk scaffolds with endothelial cells for tissue regeneration. Biomaterials 2015; 56: 68–77.
- 64Radisic M, Yang L, Boublik J, Cohen RJ, Langer R, Freed LE, Vunjak-Novakovic G. Medium perfusion enables engineering of compact and contractile cardiac tissue. Am J Physiol 2004; 286: H507–H516.
- 65Lovett M, Lee K, Edwards A, Kaplan DL. Vascularization strategies for tissue engineering. Tissue Eng B 2009; 15: 353–370.
- 66Chiu LL, Radisic M. Scaffolds with covalently immobilized VEGF and angiopoietin-1 for vascularization of engineered tissues. Biomaterials 2010; 31: 226–241.
- 67Jaquet K, Krause K, Tawakol-Khodai M, Geidel S, Kuck, K-H. Erythropoietin and VEGF exhibit equal angiogenic potential. Microvasc Res 2002; 64: 326–333.
- 68Lu D, Mahmood A, Qu C, Goussev A, Schallert T, Chopp M. Erythropoietin enhances neurogenesis and restores spatial memory in rats after traumatic brain injury. J Neurotrauma 2005; 22: 1011–1017.
- 69Efthimiadou A, Pagonopoulou O, Lambropoulou M, Papadopoulos N, Nikolettos NK. Erythropoietin enhances angiogenesis in an experimental cyclosporine a-induced nephrotoxicity model in the rat. Clin Exp Pharmacol Physiol 2007; 34: 866–869.
- 70Campana WM, Myers RR. Exogenous erythropoietin protects against dorsal root ganglion apoptosis and pain following peripheral nerve injury. Eur J Neurosci 2003; 18: 1497–1506.
- 71Keswani SC, Buldanlioglu U, Fischer A, Reed N, Polley M, Liang H, Zhou C, Jack C, Leitz GJ, Hoke A. A novel endogenous erythropoietin mediated pathway prevents axonal degeneration. Ann Neurol 2004; 56: 815–826.
- 72Yu W, Zhao W, Zhu C, Zhang X, Ye D, Zhang W, Zhou Y, Jiang X, Zhang Z. Sciatic nerve regeneration in rats by a promising electrospun collagen/poly (ɛ-caprolactone) nerve conduit with tailored degradation rate. BMC Neurosci 2011; 12: 1.
- 73Evans PJ, Mackinnon SE, Best TJ, Wade JA, Awerbuck DC, Makino AP, Hunter DA, Midha R. Regeneration across preserved peripheral nerve grafts. Muscle Nerve 1995; 18: 1128–1138.
- 74Wang X, Hu W, Cao Y, Yao J, Wu J, Gu X. Dog sciatic nerve regeneration across a 30-mm defect bridged by a chitosan/PGA artificial nerve graft. Brain 2005; 128: 1897–1910.
- 75Thomas P, Calne D. Motor nerve conduction velocity in peroneal muscular atrophy: Evidence for genetic heterogeneity. J Neurol Neurosurg Psychiatry 1974; 37: 68–75.
