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Gene therapy is a promising strategy for treating challenging diseases. The successful delivery of genes is a critical step for gene therapy. However, concerns about immunogenicity and toxicity are the main obstacles against the widespread use of effective viral systems. Therefore, nonviral vectors are regarded as good alternatives to viral vectors. Chitosan is a natural cationic polysaccharide that could be used to create nonviral gene delivery vectors. Various methods have been developed to improve the properties of chitosan related to gene delivery. A review introduces the features of chitosan in gene delivery, summarizes current progress toward methods promoting the properties of chitosan related to gene delivery, and presents different applications of chitosan in gene delivery vectors. Finally, future prospects of gene vectors based on chitosan are discussed 1).

Natural materials such as collagen and alginate have promising applications as dural substitutes. These materials are able to restore the dural defect and create optimal conditions for the development of connective tissue at the site of injury. A promising material for biomedical applications is chitosan-a linear polysaccharide obtained by the deacetylation of chitin. It has been found to be nontoxic, biodegradable, biofunctional and biocompatible in addition to having antimicrobial characteristics.

In a study Pogorielov et al., designed new chitin-chitosan substitutes for dura mater closure and evaluated their effectiveness and safety. Chitosan films were produced from 3 % of chitosan (molar mass-200, 500 or 700 kDa, deacetylation rate 80-90%) with addition of 20% of chitin. Antimicrobial effictively and cell viability were analysed for the different molar masses of chitosan. The film containing chitosan of molar mass 200 kDa, had the best antimicrobial and biological activity and was successfully used for experimental duraplasty in an in vivo model. In conclusion the chitin-chitosan membrane designed here met the requirements for a dura matter graft exhibiting the ability to support cell growth, inhibit microbial growth and biodegradade at an appropriate rate. Therefore this is a promising material for clinical duroplasty 2).

Berce et al. aimed to synthesize a polymer-based sponge containing chitosan-sodium hyaluronate-resveratrol (CHR) and to evaluate its regenerative potential. The process of synthesizing the CHR polymer was described before microtomography analysis was conducted and the density and porosity of the obtained sponges was assessed. The cytotoxicity was evaluated in vitro. By undertaking the in vivo testing of the CHR polymer, we aimed to determine the CHR sponge's potential to stimulate tissue regeneration after inflicting a controlled, reproducible and measurable skin wound in an animal model. Skin punch biopsies were harvested from the healed area and were subjected to histopathological evaluation. The results obtained in this study confirmed that this polymer accelerates the formation of granulation facilitating wound healing, while also achieving a bacteriostatic outcome 3).


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3: Skop NB, Singh S, Antikainen H, Saqcena C, Calderon F, Rothbard DE, Cho CH, Gandhi CD, Levison SW, Dobrowolski R. Subacute Transplantation of Native and Genetically Engineered Neural Progenitors Seeded on Microsphere Scaffolds Promote Repair and Functional Recovery After Traumatic Brain Injury. ASN Neuro. 2019 Jan-Dec;11:1759091419830186. doi: 10.1177/1759091419830186. PubMed PMID: 30818968; PubMed Central PMCID: PMC6399762.

4: Youssef AEH, Dief AE, El Azhary NM, Abdelmonsif DA, El-Fetiany OS. LINGO-1 siRNA nanoparticles promote central remyelination in ethidium bromide-induced demyelination in rats. J Physiol Biochem. 2019 Feb;75(1):89-99. doi: 10.1007/s13105-018-00660-6. Epub 2019 Feb 13. PubMed PMID: 30759305.

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13: Shevtsov M, Nikolaev B, Marchenko Y, Yakovleva L, Skvortsov N, Mazur A, Tolstoy P, Ryzhov V, Multhoff G. Targeting experimental orthotopic glioblastoma with chitosan-based superparamagnetic iron oxide nanoparticles (CS-DX-SPIONs). Int J Nanomedicine. 2018 Mar 12;13:1471-1482. doi: 10.2147/IJN.S152461. eCollection 2018. PubMed PMID: 29559776; PubMed Central PMCID: PMC5856030.

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20: Cupino TL, Watson BA, Cupino AC, Oda K, Ghamsary MG, Soriano S, Kirsch WM. Stability and bioactivity of chitosan as a transfection agent in primary human cell cultures: A case for chitosan-only controls. Carbohydr Polym. 2018 Jan 15;180:376-384. doi: 10.1016/j.carbpol.2017.10.021. Epub 2017 Oct 6. PubMed PMID: 29103517; PubMed Central PMCID: PMC5699233.

21: Zhao L, Niu L, Liang H, Tan H, Liu C, Zhu F. pH and Glucose Dual-Responsive Injectable Hydrogels with Insulin and Fibroblasts as Bioactive Dressings for Diabetic Wound Healing. ACS Appl Mater Interfaces. 2017 Nov 1;9(43):37563-37574. doi: 10.1021/acsami.7b09395. Epub 2017 Oct 23. PubMed PMID: 28994281.

22: Zeng W, Liu Z, Li Y, Zhu S, Ma J, Li W, Gao G. Development and characterization of cores-shell poly(lactide-co-glycolide)-chitosan microparticles for sustained release of GDNF. Colloids Surf B Biointerfaces. 2017 Nov 1;159:791-799. doi: 10.1016/j.colsurfb.2017.08.052. Epub 2017 Aug 30. PubMed PMID: 28886515.

23: Gullbrand SE, Schaer TP, Agarwal P, Bendigo JR, Dodge GR, Chen W, Elliott DM, Mauck RL, Malhotra NR, Smith LJ. Translation of an injectable triple-interpenetrating-network hydrogel for intervertebral disc regeneration in a goat model. Acta Biomater. 2017 Sep 15;60:201-209. doi: 10.1016/j.actbio.2017.07.025. Epub 2017 Jul 19. PubMed PMID: 28735027; PubMed Central PMCID: PMC5688915.

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25: Chen Q, Sun T, Song X, Ran Q, Yu C, Yang J, Feng H, Yu L, Wei D. Flexible electrochemical biosensors based on graphene nanowalls for the real-time measurement of lactate. Nanotechnology. 2017 Aug 4;28(31):315501. doi: 10.1088/1361-6528/aa78bc. Epub 2017 Jun 12. PubMed PMID: 28604366.

26: Zhao Y, Wang Y, Gong J, Yang L, Niu C, Ni X, Wang Y, Peng S, Gu X, Sun C, Yang Y. Chitosan degradation products facilitate peripheral nerve regeneration by improving macrophage-constructed microenvironments. Biomaterials. 2017 Jul;134:64-77. doi: 10.1016/j.biomaterials.2017.02.026. Epub 2017 Feb 22. PubMed PMID: 28456077.

27: Van Woensel M, Mathivet T, Wauthoz N, Rosière R, Garg AD, Agostinis P, Mathieu V, Kiss R, Lefranc F, Boon L, Belmans J, Van Gool SW, Gerhardt H, Amighi K, De Vleeschouwer S. Sensitization of glioblastoma tumor micro-environment to chemo- and immunotherapy by Galectin-1 intranasal knock-down strategy. Sci Rep. 2017 Apr 27;7(1):1217. doi: 10.1038/s41598-017-01279-1. PubMed PMID: 28450700; PubMed Central PMCID: PMC5430862.

28: Yang CL, Chen JP, Wei KC, Chen JY, Huang CW, Liao ZX. Release of Doxorubicin by a Folate-Grafted, Chitosan-Coated Magnetic Nanoparticle. Nanomaterials (Basel). 2017 Apr 13;7(4). pii: E85. doi: 10.3390/nano7040085. PubMed PMID: 28406429; PubMed Central PMCID: PMC5408177.

29: Gonzalez-Perez F, Cobianchi S, Heimann C, Phillips JB, Udina E, Navarro X. Stabilization, Rolling, and Addition of Other Extracellular Matrix Proteins to Collagen Hydrogels Improve Regeneration in Chitosan Guides for Long Peripheral Nerve Gaps in Rats. Neurosurgery. 2017 Mar 1;80(3):465-474. doi: 10.1093/neuros/nyw068. PubMed PMID: 28362971.

30: Bhatt NK, Khan TR, Mejias C, Paniello RC. Nerve transection repair using laser-activated chitosan in a rat model. Laryngoscope. 2017 Aug;127(8):E253-E257. doi: 10.1002/lary.26583. Epub 2017 Mar 27. PubMed PMID: 28349572.

31: Wu H, Lei P, Liu G, Shrike Zhang Y, Yang J, Zhang L, Xie J, Niu W, Liu H, Ruan J, Hu Y, Zhang C. Reconstruction of Large-scale Defects with a Novel Hybrid Scaffold Made from Poly(L-lactic acid)/Nanohydroxyapatite/Alendronate-loaded Chitosan Microsphere: in vitro and in vivo Studies. Sci Rep. 2017 Mar 23;7(1):359. doi: 10.1038/s41598-017-00506-z. PubMed PMID: 28337023; PubMed Central PMCID: PMC5428684.

32: Li X, Chen L, Lin H, Cao L, Cheng J, Dong J, Yu L, Ding J. Efficacy of Poly(D,L-Lactic Acid-co-Glycolic acid)-Poly(Ethylene Glycol)-Poly(D,L-Lactic Acid-co-Glycolic Acid) Thermogel As a Barrier to Prevent Spinal Epidural Fibrosis in a Postlaminectomy Rat Model. Clin Spine Surg. 2017 Apr;30(3):E283-E290. doi: 10.1097/BSD.0000000000000221. PubMed PMID: 28323713.

33: Rajiv S, Drilling A, Bassiouni A, Harding M, James C, Robinson S, Moratti S, Wormald PJ. Chitosan Dextran gel as an anti adhesion agent in a postlaminectomy spinal sheep model. J Clin Neurosci. 2017 Jun;40:153-156. doi: 10.1016/j.jocn.2017.02.010. Epub 2017 Mar 11. PubMed PMID: 28291642.

34: Muheremu A, Chen L, Wang X, Wei Y, Gong K, Ao Q. Chitosan nerve conduits seeded with autologous bone marrow mononuclear cells for 30 mm goat peroneal nerve defect. Sci Rep. 2017 Mar 13;7:44002. doi: 10.1038/srep44002. PubMed PMID: 28287100; PubMed Central PMCID: PMC5347120.

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37: Yun Q, Wang SS, Xu S, Yang JP, Fan J, Yang LL, Chen Y, Fu SZ, Wu JB. Use of 5-Fluorouracil Loaded Micelles and Cisplatin in Thermosensitive Chitosan Hydrogel as an Efficient Therapy against Colorectal Peritoneal Carcinomatosis. Macromol Biosci. 2017 Apr;17(4). doi: 10.1002/mabi.201600262. Epub 2016 Oct 20. PubMed PMID: 27762505.

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40: Yue W, Yan F, Zhang YL, Liu SL, Hou SP, Mao GC, Liu N, Ji Y. Differentiation of Rat Bone Marrow Mesenchymal Stem Cells Into Neuron-Like Cells In Vitro and Co-Cultured with Biological Scaffold as Transplantation Carrier. Med Sci Monit. 2016 May 26;22:1766-72. PubMed PMID: 27225035; PubMed Central PMCID: PMC4917310.

41: Huang C, Zhao L, Gu J, Nie D, Chen Y, Zuo H, Huan W, Shi J, Chen J, Shi W. The migration and differentiation of hUC-MSCs(CXCR4/GFP) encapsulated in BDNF/chitosan scaffolds for brain tissue engineering. Biomed Mater. 2016 May 5;11(3):035004. doi: 10.1088/1748-6041/11/3/035004. PubMed PMID: 27147644.

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46: Crofton A, Chrisler J, Hudson S, Inceoglu S, Petersen F, Kirsch W. Effect of Plasma Sterilization on the Hemostatic Efficacy of a Chitosan Hemostatic Agent in a Rat Model. Adv Ther. 2016 Feb;33(2):268-81. doi: 10.1007/s12325-016-0289-6. Epub 2016 Jan 30. PubMed PMID: 26833305.

47: Zhou Y, Zhao J, Sun X, Li S, Hou X, Yuan X, Yuan X. Rapid Gelling Chitosan/Polylysine Hydrogel with Enhanced Bulk Cohesive and Interfacial Adhesive Force: Mimicking Features of Epineurial Matrix for Peripheral Nerve Anastomosis. Biomacromolecules. 2016 Feb 8;17(2):622-30. doi: 10.1021/acs.biomac.5b01550. Epub 2016 Jan 27. PubMed PMID: 26779667.

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52: Ni S, Xia T, Li X, Zhu X, Qi H, Huang S, Wang J. Sustained delivery of chondroitinase ABC by poly(propylene carbonate)-chitosan micron fibers promotes axon regeneration and functional recovery after spinal cord hemisection. Brain Res. 2015 Oct 22;1624:469-478. doi: 10.1016/j.brainres.2015.08.018. Epub 2015 Aug 24. PubMed PMID: 26315376.

53: Ning X, Zhao C, Pang J, Ding Z, Wang Y, Xu K, Chen H, Li B, Luo QI. Experimental study of temperature-sensitive chitosan/β-glycerophosphate embolic material in embolizing the basicranial rete mirabile in swines. Exp Ther Med. 2015 Jul;10(1):316-322. Epub 2015 May 7. PubMed PMID: 26170955; PubMed Central PMCID: PMC4486800.

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57: Shapira Y, Tolmasov M, Nissan M, Reider E, Koren A, Biron T, Bitan Y, Livnat M, Ronchi G, Geuna S, Rochkind S. Comparison of results between chitosan hollow tube and autologous nerve graft in reconstruction of peripheral nerve defect: An experimental study. Microsurgery. 2016 Nov;36(8):664-671. doi: 10.1002/micr.22418. Epub 2015 Apr 22. PubMed PMID: 25899554.

58: Jian R, Yixu Y, Sheyu L, Jianhong S, Yaohua Y, Xing S, Qingfeng H, Xiaojian L, Lei Z, Yan Z, Fangling X, Huasong G, Yilu G. Repair of spinal cord injury by chitosan scaffold with glioma ECM and SB216763 implantation in adult rats. J Biomed Mater Res A. 2015 Oct;103(10):3259-72. doi: 10.1002/jbm.a.35466. Epub 2015 Apr 1. PubMed PMID: 25809817.

59: Lindborg BA, Brekke JH, Scott CM, Chai YW, Ulrich C, Sandquist L, Kokkoli E, O'Brien TD. A chitosan-hyaluronan-based hydrogel-hydrocolloid supports in vitro culture and differentiation of human mesenchymal stem/stromal cells. Tissue Eng Part A. 2015 Jun;21(11-12):1952-62. doi: 10.1089/ten.TEA.2014.0335. Epub 2015 Apr 20. PubMed PMID: 25748146.

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61: Liu Z, Huang L, Liu L, Luo B, Liang M, Sun Z, Zhu S, Quan X, Yang Y, Ma T, Huang J, Luo Z. Activation of Schwann cells in vitro by magnetic nanocomposites via applied magnetic field. Int J Nanomedicine. 2014 Dec 17;10:43-61. doi: 10.2147/IJN.S74332. eCollection 2015. PubMed PMID: 25565803; PubMed Central PMCID: PMC4275057.

62: Xu H, Nie X, Wu L, Zhu X, Yi W, Huang S. Down-Regulation of MRP1 Expression in C6/VP16 Cells by Chitosan-MRP1-siRNA Nanoparticles. Cell Biochem Biophys. 2015 May;72(1):227-33. doi: 10.1007/s12013-014-0442-2. PubMed PMID: 25543328.

63: Farahpour MR, Ghayour SJ. Effect of in situ delivery of acetyl-L-carnitine on peripheral nerve regeneration and functional recovery in transected sciatic nerve in rat. Int J Surg. 2014 Dec;12(12):1409-15. doi: 10.1016/j.ijsu.2014.10.023. Epub 2014 Oct 28. PubMed PMID: 25448663.

64: Tian M, Han B, Tan H, You C. Preparation and characterization of galactosylated alginate-chitosan oligomer microcapsule for hepatocytes microencapsulation. Carbohydr Polym. 2014 Nov 4;112:502-11. doi: 10.1016/j.carbpol.2014.06.025. Epub 2014 Jun 19. PubMed PMID: 25129774.

65: Shirosaki Y, Hayakawa S, Osaka A, Lopes MA, Santos JD, Geuna S, Mauricio AC. Challenges for nerve repair using chitosan-siloxane hybrid porous scaffolds. Biomed Res Int. 2014;2014:153808. doi: 10.1155/2014/153808. Epub 2014 Jun 17. Review. PubMed PMID: 25054129; PubMed Central PMCID: PMC4087280.

66: Barton MJ, Morley JW, Stoodley MA, Lauto A, Mahns DA. Nerve repair: toward a sutureless approach. Neurosurg Rev. 2014 Oct;37(4):585-95. doi: 10.1007/s10143-014-0559-1. Epub 2014 Jul 13. Review. PubMed PMID: 25015388.

67: Li C, Wang H, Liu H, Yin J, Cui L, Chen Z. The prevention effect of poly (L-glutamic acid)/chitosan on spinal epidural fibrosis and peridural adhesion in the post-laminectomy rabbit model. Eur Spine J. 2014 Nov;23(11):2423-31. doi: 10.1007/s00586-014-3438-0. Epub 2014 Jul 8. PubMed PMID: 25001891.

68: Zeng W, Rong M, Hu X, Xiao W, Qi F, Huang J, Luo Z. Incorporation of chitosan microspheres into collagen-chitosan scaffolds for the controlled release of nerve growth factor. PLoS One. 2014 Jul 1;9(7):e101300. doi: 10.1371/journal.pone.0101300. eCollection 2014. PubMed PMID: 24983464; PubMed Central PMCID: PMC4077743.

69: Carvalho M, Costa LM, Pereira JE, Shirosaki Y, Hayakawa S, Santos JD, Geuna S, Fregnan F, Cabrita AM, Maurício AC, Varejão AS. The role of hybrid chitosan membranes on scarring process following lumbar surgery: post-laminectomy experimental model. Neurol Res. 2015 Jan;37(1):23-9. doi: 10.1179/1743132814Y.0000000414. Epub 2014 Jun 25. PubMed PMID: 24965895.

70: Tseng TT, Chang CF, Chan WC. Fabrication of implantable, enzyme-immobilized glutamate sensors for the monitoring of glutamate concentration changes in vitro and in vivo. Molecules. 2014 Jun 5;19(6):7341-55. doi: 10.3390/molecules19067341. PubMed PMID: 24905604; PubMed Central PMCID: PMC6271204.

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Chuan D, Jin T, Fan R, Zhou L, Guo G. Chitosan for gene delivery: Methods for improvement and applications. Adv Colloid Interface Sci. 2019 Mar 21;268:25-38. doi: 10.1016/j.cis.2019.03.007. [Epub ahead of print] Review. PubMed PMID: 30933750.
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chitosan.txt · Last modified: 2019/04/02 22:26 by administrador