Synthesis and fabrication of films including graphene oxide functionalized with chitosan for regenerative medicine applications

Graphene oxide (GO) has recently gained attention as a scaffold reinforcing agent for tissue engineering. Biomechanical and biological properties through a synergistic effect can be strengthened when combined with other materials such as chitosan (CS). For that reason, chitosan was used for Graphene...

Full description

Autores:
Valencia, Ana María
Tipo de recurso:
Fecha de publicación:
2020
Institución:
Universidad del Atlántico
Repositorio:
Repositorio Uniatlantico
Idioma:
eng
OAI Identifier:
oai:repositorio.uniatlantico.edu.co:20.500.12834/1145
Acceso en línea:
https://hdl.handle.net/20.500.12834/1145
Palabra clave:
Chitosan Graphene oxide Regenerative medicine Tissue engineering
Rights
openAccess
License
http://creativecommons.org/licenses/by-nc/4.0/
id UNIATLANT2_70dc54ac41d2dff6fbc06ea5c1f229c3
oai_identifier_str oai:repositorio.uniatlantico.edu.co:20.500.12834/1145
network_acronym_str UNIATLANT2
network_name_str Repositorio Uniatlantico
repository_id_str
dc.title.spa.fl_str_mv Synthesis and fabrication of films including graphene oxide functionalized with chitosan for regenerative medicine applications
dc.title.alternative.spa.fl_str_mv Synthesis and fabrication of films including graphene oxide functionalized with chitosan for regenerative medicine applications
title Synthesis and fabrication of films including graphene oxide functionalized with chitosan for regenerative medicine applications
spellingShingle Synthesis and fabrication of films including graphene oxide functionalized with chitosan for regenerative medicine applications
Chitosan Graphene oxide Regenerative medicine Tissue engineering
title_short Synthesis and fabrication of films including graphene oxide functionalized with chitosan for regenerative medicine applications
title_full Synthesis and fabrication of films including graphene oxide functionalized with chitosan for regenerative medicine applications
title_fullStr Synthesis and fabrication of films including graphene oxide functionalized with chitosan for regenerative medicine applications
title_full_unstemmed Synthesis and fabrication of films including graphene oxide functionalized with chitosan for regenerative medicine applications
title_sort Synthesis and fabrication of films including graphene oxide functionalized with chitosan for regenerative medicine applications
dc.creator.fl_str_mv Valencia, Ana María
dc.contributor.author.none.fl_str_mv Valencia, Ana María
dc.contributor.other.none.fl_str_mv Valencia, Carlos Humberto
Zuluaga, Fabio
Grande-Tovar, Carlos David
dc.subject.keywords.spa.fl_str_mv Chitosan Graphene oxide Regenerative medicine Tissue engineering
topic Chitosan Graphene oxide Regenerative medicine Tissue engineering
description Graphene oxide (GO) has recently gained attention as a scaffold reinforcing agent for tissue engineering. Biomechanical and biological properties through a synergistic effect can be strengthened when combined with other materials such as chitosan (CS). For that reason, chitosan was used for Graphene Oxide (GO) functionalization through an amide group whose formation was evident by bands around 1600 cm 1 in the FTIR analysis. Furthermore, bands located at 1348 cm 1 (D band), 1593 cm 1 (G band), and 2416 cm 1 (2D band) in the RAMAN spectrum, and the displacement of the signal at 87.03 ppm (C5) in solid-state 13C-NMR confirmed the amide formation. Films including the CS-GO compound were prepared and characterized by thermogravimetric analysis (TGA), where CS-GO film presented a lighter mass loss (~10% less loosed) than CS due probably to the covalent functionalization with GO, providing film thermal resistance. The CS-GO films synthesized were implanted in Wistar rats' subdermal tissue as a first approximation to the biological response. In vivo tests showed a low inflammatory response, good cicatrization, and advanced resorption at 60 days of implantation, as indicated by histological images. It was evidenced that the covalent union between CS and GO increased biocompatibility and the degradation/resorption capacity, demonstrating tissue regeneration with typical characteristics and tiny remnants of implanted material surrounded by a type III collagen capsule. These results show the potential application of the new synthesized films, including the CS-GO compound, in tissue engineering.
publishDate 2020
dc.date.submitted.none.fl_str_mv 2020-07-22
dc.date.issued.none.fl_str_mv 2021-06-12
dc.date.accessioned.none.fl_str_mv 2022-12-19T02:43:01Z
dc.date.available.none.fl_str_mv 2022-12-19T02:43:01Z
dc.type.coarversion.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/article
dc.type.hasVersion.spa.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.spa.spa.fl_str_mv Artículo
status_str publishedVersion
dc.identifier.citation.spa.fl_str_mv Valencia AM, Valencia CH, Zuluaga F, Grande-Tovar CD. Synthesis and fabrication of films including graphene oxide functionalized with chitosan for regenerative medicine applications. Heliyon. 2021 May 21;7(5):e07058. doi: 10.1016/j.heliyon.2021.e07058. PMID: 34095569; PMCID: PMC8165423.
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12834/1145
dc.identifier.doi.none.fl_str_mv 10.1016/j.heliyon.2021.e07058.
dc.identifier.instname.spa.fl_str_mv Universidad del Atlántico
dc.identifier.reponame.spa.fl_str_mv Repositorio Universidad del Atlántico
identifier_str_mv Valencia AM, Valencia CH, Zuluaga F, Grande-Tovar CD. Synthesis and fabrication of films including graphene oxide functionalized with chitosan for regenerative medicine applications. Heliyon. 2021 May 21;7(5):e07058. doi: 10.1016/j.heliyon.2021.e07058. PMID: 34095569; PMCID: PMC8165423.
10.1016/j.heliyon.2021.e07058.
Universidad del Atlántico
Repositorio Universidad del Atlántico
url https://hdl.handle.net/20.500.12834/1145
dc.language.iso.spa.fl_str_mv eng
language eng
dc.rights.coar.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.rights.uri.*.fl_str_mv http://creativecommons.org/licenses/by-nc/4.0/
dc.rights.cc.*.fl_str_mv Attribution-NonCommercial 4.0 International
dc.rights.accessRights.spa.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc/4.0/
Attribution-NonCommercial 4.0 International
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.mimetype.spa.fl_str_mv application/pdf
dc.publisher.place.spa.fl_str_mv Barranquilla
dc.publisher.discipline.spa.fl_str_mv Química
dc.publisher.sede.spa.fl_str_mv Sede Norte
dc.source.spa.fl_str_mv Heliyon
institution Universidad del Atlántico
bitstream.url.fl_str_mv https://repositorio.uniatlantico.edu.co/bitstream/20.500.12834/1145/1/1-s2.0-S2405844021011610-main.pdf
https://repositorio.uniatlantico.edu.co/bitstream/20.500.12834/1145/2/license_rdf
https://repositorio.uniatlantico.edu.co/bitstream/20.500.12834/1145/3/license.txt
bitstream.checksum.fl_str_mv c6c580a17c96a78ad1b7117b2ac29bad
24013099e9e6abb1575dc6ce0855efd5
67e239713705720ef0b79c50b2ececca
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
repository.name.fl_str_mv DSpace de la Universidad de Atlántico
repository.mail.fl_str_mv sysadmin@mail.uniatlantico.edu.co
_version_ 1814203421426712576
spelling Valencia, Ana Maríabe3f2f77-a67c-4e97-9ac6-8af5d40a61f8Valencia, Carlos HumbertoZuluaga, FabioGrande-Tovar, Carlos David2022-12-19T02:43:01Z2022-12-19T02:43:01Z2021-06-122020-07-22Valencia AM, Valencia CH, Zuluaga F, Grande-Tovar CD. Synthesis and fabrication of films including graphene oxide functionalized with chitosan for regenerative medicine applications. Heliyon. 2021 May 21;7(5):e07058. doi: 10.1016/j.heliyon.2021.e07058. PMID: 34095569; PMCID: PMC8165423.https://hdl.handle.net/20.500.12834/114510.1016/j.heliyon.2021.e07058.Universidad del AtlánticoRepositorio Universidad del AtlánticoGraphene oxide (GO) has recently gained attention as a scaffold reinforcing agent for tissue engineering. Biomechanical and biological properties through a synergistic effect can be strengthened when combined with other materials such as chitosan (CS). For that reason, chitosan was used for Graphene Oxide (GO) functionalization through an amide group whose formation was evident by bands around 1600 cm 1 in the FTIR analysis. Furthermore, bands located at 1348 cm 1 (D band), 1593 cm 1 (G band), and 2416 cm 1 (2D band) in the RAMAN spectrum, and the displacement of the signal at 87.03 ppm (C5) in solid-state 13C-NMR confirmed the amide formation. Films including the CS-GO compound were prepared and characterized by thermogravimetric analysis (TGA), where CS-GO film presented a lighter mass loss (~10% less loosed) than CS due probably to the covalent functionalization with GO, providing film thermal resistance. The CS-GO films synthesized were implanted in Wistar rats' subdermal tissue as a first approximation to the biological response. In vivo tests showed a low inflammatory response, good cicatrization, and advanced resorption at 60 days of implantation, as indicated by histological images. It was evidenced that the covalent union between CS and GO increased biocompatibility and the degradation/resorption capacity, demonstrating tissue regeneration with typical characteristics and tiny remnants of implanted material surrounded by a type III collagen capsule. These results show the potential application of the new synthesized films, including the CS-GO compound, in tissue engineering.application/pdfenghttp://creativecommons.org/licenses/by-nc/4.0/Attribution-NonCommercial 4.0 Internationalinfo:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2HeliyonSynthesis and fabrication of films including graphene oxide functionalized with chitosan for regenerative medicine applicationsSynthesis and fabrication of films including graphene oxide functionalized with chitosan for regenerative medicine applicationsPúblico generalChitosan Graphene oxide Regenerative medicine Tissue engineeringinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArtículohttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_2df8fbb1BarranquillaQuímicaSede NorteM.A. Nguyen, G. Camci-unal Unconventional tissue engineering materials in disguise Trends Biotechnol., 1–13 (2019)S. Saber-Samandari, S. Saber-Samandari Biocompatible nanocomposite scaffolds based on copolymer-grafted chitosan for bone tissue engineering with drug delivery capability Mater. Sci. Eng. C, 75 (2017), pp. 721-732A. Abedi, M. Hasanzadeh, L. Tayebi Conductive nanofibrous chitosan/PEDOT:PSS tissue engineering scaffolds Mater. Chem. Phys., 237 (October 2018) (2019), p. 121882L.A. Loureiro dos Santos Natural polymeric biomaterials: processing and properties Ref. Modul. Mater. Sci. Mater. Eng. (2017), pp. 1-6K. Balagangadharan, S. Dhivya, N. Selvamurugan Chitosan based nanofibers in bone tissue engineering Int. J. Biol. Macromol., 104 (2017), pp. 1372-1382A. Muxika, A. Etxabide, J. Uranga, P. Guerrero, K. de la Caba Chitosan as a bioactive polymer: processing, properties and applications Int. J. Biol. Macromol., 105 (2017), pp. 1358-1368S.M. Ahsan, M. Thomas, K.K. Reddy, S.G. Sooraparaju, A. Asthana, I. Bhatnagar Chitosan as biomaterial in drug delivery and tissue engineering Int. J. Biol. Macromol., 110 (2017), pp. 97-109F. Tao, Y. Cheng, X. Shi, H. Zheng, Y. Du, W. Xiang, H. Deng Applications of chitin and chitosan nanofibers in bone regenerative engineering Carbohydr. Polym., 230 (October 2019) (2019), p. 115658.Z. Knaul, S.M. Hudson, K.A.M. Creber Improved mechanical properties of chitosan fibers J. Appl. Polym. Sci., 72 (13) (1999), pp. 1721-1732K. Pieklarz, M. Tylman, Z. Modrzejewska Current progress in biomedical applications of chitosan-carbon nanotube nanocomposites: a review Mini Rev. Med. Chem., 20 (16) (2020), pp. 1619-1632D.C. Grande Tovar, I.J. Castro, H.C. Valencia, P.D. Navia Porras, J. Herminsul Mina Hernandez, E.M. Valencia Zapata, N.M. Chaur Nanocomposite films of chitosan-grafted carbon nano-onions for biomedical applications Molecules (2020)C.D. Grande Tovar, J.I. Castro, C.H. Valencia, D.P. Navia Porras, M. Hernandez, J. Herminsul, M.E. Valencia, J.D. Velásquez, M.N. Chaur Preparation of chitosan/poly (vinyl alcohol) nanocomposite films incorporated with oxidized carbon nano-onions (Multi-Layer fullerenes) for tissue-engineering applications Biomolecules, 9 (11) (2019), p. 684B. Sharma, S. Shekhar, P. Jain, R. Sharma, K.K.D. Chauhan Graphene grafted chitosan nanocomposites and their applications Graphene Based Biopolymer Nanocomposites, Springer (2021), pp. 135-147A. Raslan, L.S. Del Burgo, J. Ciriza, J.L. Pedraz Graphene oxide and reduced graphene oxide-based scaffolds in regenerative medicine Int. J. Pharm., 580 (2020), p. 119226D.C. Grande Tovar, I.J. Castro, H.C. Valencia, A.P. Zapata, A.M. Solano, E. Florez López, N.M. Chaur, E.M. Valencia Zapata, H.J. Mina Hernandez Synthesis of chitosan beads incorporating graphene oxide/titanium dioxide nanoparticles for in vivo studies Molecules (2020)S.C. Ray Application and Uses of Graphene Oxide and Reduced Graphene Oxide Elsevier Inc. (2015)V. Gupta, N. Sharma, U. Singh, M. Arif, A. Singh Higher oxidation level in graphene oxide Optik, 143 (2017), pp. 115-124A.T. Smith, A.M. LaChance, S. Zeng, B. Liu, L. Sun Synthesis, properties, and applications of graphene oxide/reduced graphene oxide and their nanocomposites Nano Mater. Sci., 1 (1) (2019), pp. 31-47B. Yang, P.-B. Wang, N. Mu, K. Ma, S. Wang, C.-Y. Yang, Z.-B. Huang, Y. Lai, H. Feng, G.-F. Yin Graphene oxide-composited chitosan scaffold contributes to functional recovery of injured spinal cord in rats Neural Regen. Res., 16 (9) (2021), p. 1829C. Xie, X. Lu, L. Han, J. Xu, Z. Wang, L. Jiang, K. Wang, H. Zhang, F. Ren, Y. Tang Biomimetic mineralized hierarchical graphene oxide/chitosan scaffolds with adsorbability for immobilization of nanoparticles for biomedical applications ACS Appl. Mater. Interfaces, 8 (3) (2016), pp. 1707-1717H. Yi, L.Q. Wu, W.E. Bentley, R. Ghodssi, G.W. Rubloff, J.N. Culver, G.F. Payne Biofabrication with chitosan Biomacromolecules, 6 (6) (2005), pp. 2881-2894F. Saeedi, A. Montazeri, Y. Bahari, M. Pishvaei, B. Jannat, M. Rasa, F. Saeedi Fabrication and characterization of chitosan-polyvinyl alcohol-graphene oxide nanocomposite scaffold for wound healing purposes Human, Heal. Halal Metrics, 1 (2) (2021), pp. 47-55N. Amiryaghoubi, M. Fathi, A. Barzegari, J. Barar, H. Omidian, Y. Omidi Recent advances in polymeric scaffolds containing carbon nanotube and graphene oxide for cartilage and bone regeneration Mater. Today Commun. (2021), p. 102097P.P. Zuo, H.F. Feng, Z.Z. Xu, L.F. Zhang, Y.L. Zhang, W. Xia, W.Q. Zhang Fabrication of biocompatible and mechanically reinforced graphene oxide-chitosan nanocomposite films Chem. Cent. J., 7 (1) (2013), pp. 1-11D.L. Tenorio, C.H. Valencia, C. Valencia, F. Zuluaga, M.E. Valencia, J.H. Mina, C.D.G. Tovar Evaluation of the biocompatibility of Cs-graphene oxide compounds in vivo Int. J. Mol. Sci., 20 (7) (2019)C. Valencia, C.H. Valencia, F. Zuluaga, M.E. Valencia, J.H. Mina, C.D. Grande-Tovar Synthesis and application of scaffolds of chitosan-graphene oxide by the freeze-drying method for tissue regeneration Molecules, 23 (10) (2018)S. Biranje, P. Madiwale, A.R.V. Adicarekar Preparation and characterization of chitosan/pva polymeric film for its potential application as wound dressing Material. Indian J.Sci. Res, 14 (2) (2017), pp. 250-256T. Ramanathan, A.A. Abdala, S. Stankovich, D.A. Dikin, M. Herrera-Alonso, R.D. Piner, D.H. Adamson, H.C. Schniepp, X. Chen, R.S. Ruoff, S.T. Nguyen, I.A. Aksay, R.K. Prud’Homme, L.C. Brinson Functionalized graphene sheets for polymer nanocomposites Nat. Nanotechnol., 3 (6) (2008), pp. 327-331S.H.M. Wong, S.S. Lim, T.J. Tiong, P.L. Show, H.F.M. Zaid, H.-S. Loh Preliminary in vitro evaluation of chitosan–graphene oxide scaffolds on osteoblastic adhesion, proliferation, and early differentiation Int. J. Mol. Sci., 21 (15) (2020), p. 5202L. Carson, C. Kelly-Brown, M. Stewart, A. Oki, G. Regisford, Z. Luo, V.I. Bakhmutov Synthesis and characterization of chitosan-carbon nanotube composites Mater. Lett., 63 (6–7) (2009), pp. 617-620Snežzana Miljanić, Leo Frkanec, Tomislav Biljan, Zlatko Meić Mladen Žini Recent advances in linear and nonlinear Raman spectroscopy I J. Raman Spectrosc., 38 (April) (2007), pp. 1538-1553D.C. Marcano, D.V. Kosynkin, J.M. Berlin, A. Sinitskii, Z. Sun, A. Slesarev, L.B. Alemany, W. Lu, J.M. Tour Improved synthesis of graphene oxide ACS Nano, 4 (8) (2010), pp. 4806-4814D. López-Díaz, M. López Holgado, J.L. García-Fierro, M.M. Velázquez Evolution of the Raman spectrum with the chemical composition of graphene oxide J. Phys. Chem. C, 121 (37) (2017), pp. 20489-20497D. Ma, X. Li, Y. Guo, Y. Zeng Study on IR properties of reduced graphene oxide IOP Conf. Ser. Earth Environ. Sci., 108 (2) (2018)Y. Pan, T. Wu, H. Bao, L. Li Green fabrication of chitosan films reinforced with parallel aligned graphene oxide Carbohydr. Polym., 83 (4) (2011), pp. 1908-1915K.S.S.K. Muhamad, F. Mohamed, S. Radiman, A. Hamzah, S. Sarmani, K.K. Siong, M.S. Yasir, I.A. Rahman, N.R.A.M. Rosli Synthesis and characterization of exfoliated graphene oxide AIP Conf. Proc. (2016), p. 1784D. Han, L. Yan, W. Chen, W. Li Preparation of chitosan/graphene oxide composite film with enhanced mechanical strength in the wet state Carbohydr. Polym., 83 (2) (2011), pp. 653-658M.S. Muda, A. Kamari, S.A. Bakar, S.N.M. Yusoff, I. Fatimah, E. Phillip, S.M. Din Chitosan-graphene oxide nanocomposites as water-solubilising agents for rotenone pesticide J. Mol. Liq., 318 (2020), p. 114066W.F. Khalil, G.S. El-Sayyad, W.M.A. El Rouby, M.A. Sadek, A.A. Farghali, A.I. El-Batal Graphene oxide-based nanocomposites (GO-Chitosan and GO-EDTA) for outstanding antimicrobial potential against some Candida species and pathogenic bacteria Int. J. Biol. Macromol., 164 (2020), pp. 1370-1383C. Qin, H. Li, Q. Xiao, Y. Liu, J. Zhu, Y. Du Water-solubility of chitosan and its antimicrobial activity Carbohydr. Polym., 63 (3) (2006), pp. 367-374G. Muñoz, C. Valencia, N. Valderruten, E. Ruiz-Durántez, F. Zuluaga Extraction of chitosan from Aspergillus Niger mycelium and synthesis of hydrogels for controlled release of betahistine React. Funct. Polym., 91–92 (June) (2015), pp. 1-10E.S. Alvarenga Characterization and properties of chitosan Biotechnol. Biopolym. (2011), pp. 91-108I. Younes, S. Hajji, V. Frachet, M. Rinaudo, K. Jellouli, M. Nasri Chitin extraction from shrimp shell using enzymatic treatment. Antitumor, antioxidant and antimicrobial activities of chitosan Int. J. Biol. Macromol., 69 (2014), pp. 489-498A.B. Muley, S.A. Chaudhari, K.H. Mulchandani, R.S. Singhal Extraction and characterization of chitosan from prawn shell waste and its conjugation with cutinase for enhanced thermo-stability Int. J. Biol. Macromol., 111 (2018), pp. 1047-1050P.G. Ren, D.X. Yan, X. Ji, T. Chen, Z.M. Li Temperature dependence of graphene oxide reduced by hydrazine hydrate Nanotechnology, 22 (5) (2011)P. de A. Sarmento, T. da R. Ataíde, A.P. de S. Pinto, J.X. de Araújo-Júnior, I.M.L. Lúcio, M.L. de A. Bastos Avaliação do extrato da zeyheria tuberculosa Na perspectiva de Um produto para cicatrização de Feridas Rev. Lat. Am. Enfermagem, 22 (1) (2014), pp. 165-172M. Jannasch, T. Weigel, L. Engelhardt, J. Wiezoreck, S. Gaetzner, H. Walles, T. Schmitz, J. Hansmann In vitro chemotaxis and tissue remodeling assays quantitatively characterize foreign body reaction ALTEX, 34 (2) (2017), pp. 253-266M. Tomida, K. Nakano, S. Matsuura, T. K Comparative examination of subcutaneous tissue reation to high molecular materials in medical use Eur. J. Med. Res. (2011), pp. 249-252S. Al-Maawi, C. Mota, A. Kubesch, C. James Kirkpatrick, L. Moroni, S. Ghanaati Multiwell three-dimensional systems enable in vivo screening of immune reactions to biomaterials: a new strategy toward translational biomaterial research J. Mater. Sci. Mater. Med., 30 (6) (2019), pp. 1-6J.M. Anderson, A. Rodriguez, D.T. Chang Foreign body reaction to biomaterials Semin. Immunol., 20 (2) (2008), pp. 86-100D.S. Steinbrech, M.T. Longaker, B.J. Mehrara, P.B. Saadeh, G.S. Chin, R.P. Gerrets, D.C. Chau, N.M. Rowe, G.K. Gittes Fibroblast response to hypoxia: the relationship between angiogenesis and matrix regulation J. Surg. Res., 84 (2) (1999), pp. 127-133P. Kumar, S. Kumar, E.P. Udupa, U. Kumar, P. Rao, T. Honnegowda Role of angiogenesis and angiogenic factors in acute and chronic wound healing Plast. Aesthetic Res., 2 (5) (2015), p. 243S.M. Sari Kiliçaslan, Ş. Coşkun Cevher, E.G. Güleç Peker Ultrastructural changes in blood vessels in epidermal growth factor treated experimental cutaneous wound model Pathol. Res. Pract., 209 (11) (2013), pp. 710-715M.R. Major, V.W. Wong, E.R. Nelson, M.T. Longaker, G.C. Gurtner The foreign body response: at the interface of surgery and bioengineering Plast. Reconstr. Surg., 135 (5) (2015), pp. 1489-1498http://purl.org/coar/resource_type/c_2df8fbb1ORIGINAL1-s2.0-S2405844021011610-main.pdf1-s2.0-S2405844021011610-main.pdfapplication/pdf3010942https://repositorio.uniatlantico.edu.co/bitstream/20.500.12834/1145/1/1-s2.0-S2405844021011610-main.pdfc6c580a17c96a78ad1b7117b2ac29badMD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8914https://repositorio.uniatlantico.edu.co/bitstream/20.500.12834/1145/2/license_rdf24013099e9e6abb1575dc6ce0855efd5MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81306https://repositorio.uniatlantico.edu.co/bitstream/20.500.12834/1145/3/license.txt67e239713705720ef0b79c50b2ececcaMD5320.500.12834/1145oai:repositorio.uniatlantico.edu.co:20.500.12834/11452022-12-18 21:43:02.208DSpace de la Universidad de Atlánticosysadmin@mail.uniatlantico.edu.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

Publicaciones similares