Diseño de una tinta de biomaterial a base de pegda y plasma rico en plaquetas para potenciales aplicaciones en el desarrollo de apósitos personalizados para úlceras crónicas de pie diabético
Las úlceras crónicas de pie diabético (UCPD) son una problemática que afecta la integridad de la piel, la cual necesita de una matriz extracelular (andamio) y biomoléculas para lograr el proceso cicatrización. Las biomoléculas inmersas en el plasma rico en plaquetas (PRP), incluyen factores de creci...
- Autores:
-
Mateus Suárez, Sofia Valentina
Torres Pinzón, Michelle María
- Tipo de recurso:
- Trabajo de grado de pregrado
- Fecha de publicación:
- 2021
- Institución:
- Universidad Autónoma de Bucaramanga - UNAB
- Repositorio:
- Repositorio UNAB
- Idioma:
- spa
- OAI Identifier:
- oai:repository.unab.edu.co:20.500.12749/13790
- Acceso en línea:
- http://hdl.handle.net/20.500.12749/13790
- Palabra clave:
- Biomedical engineering
Engineering
Medical electronics
Biological physics
Bioengineering
Medical instruments and apparatus
Medicine
Pegda
3D bioprinting
Biomaterial ink
CDFU
Foot diseases
Biomolecules
Ingeniería biomédica
Ingeniería
Biofísica
Bioingeniería
Medicina
Enfermedades de los pies
Biomoléculas
Ingeniería clínica
Clinical engineering
Electrónica médica
Instrumentos y aparatos médicos
Pegda
Bioimpresión 3D
Tinta de biomaterial
PRP
UCPD
- Rights
- openAccess
- License
- http://creativecommons.org/licenses/by-nc-nd/2.5/co/
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| dc.title.spa.fl_str_mv |
Diseño de una tinta de biomaterial a base de pegda y plasma rico en plaquetas para potenciales aplicaciones en el desarrollo de apósitos personalizados para úlceras crónicas de pie diabético |
| dc.title.translated.spa.fl_str_mv |
Design of a pegda-based biomaterial ink and platelet-rich plasma for potential applications in the development of personalized dressings for chronic diabetic foot ulcers |
| title |
Diseño de una tinta de biomaterial a base de pegda y plasma rico en plaquetas para potenciales aplicaciones en el desarrollo de apósitos personalizados para úlceras crónicas de pie diabético |
| spellingShingle |
Diseño de una tinta de biomaterial a base de pegda y plasma rico en plaquetas para potenciales aplicaciones en el desarrollo de apósitos personalizados para úlceras crónicas de pie diabético Biomedical engineering Engineering Medical electronics Biological physics Bioengineering Medical instruments and apparatus Medicine Pegda 3D bioprinting Biomaterial ink CDFU Foot diseases Biomolecules Ingeniería biomédica Ingeniería Biofísica Bioingeniería Medicina Enfermedades de los pies Biomoléculas Ingeniería clínica Clinical engineering Electrónica médica Instrumentos y aparatos médicos Pegda Bioimpresión 3D Tinta de biomaterial PRP UCPD |
| title_short |
Diseño de una tinta de biomaterial a base de pegda y plasma rico en plaquetas para potenciales aplicaciones en el desarrollo de apósitos personalizados para úlceras crónicas de pie diabético |
| title_full |
Diseño de una tinta de biomaterial a base de pegda y plasma rico en plaquetas para potenciales aplicaciones en el desarrollo de apósitos personalizados para úlceras crónicas de pie diabético |
| title_fullStr |
Diseño de una tinta de biomaterial a base de pegda y plasma rico en plaquetas para potenciales aplicaciones en el desarrollo de apósitos personalizados para úlceras crónicas de pie diabético |
| title_full_unstemmed |
Diseño de una tinta de biomaterial a base de pegda y plasma rico en plaquetas para potenciales aplicaciones en el desarrollo de apósitos personalizados para úlceras crónicas de pie diabético |
| title_sort |
Diseño de una tinta de biomaterial a base de pegda y plasma rico en plaquetas para potenciales aplicaciones en el desarrollo de apósitos personalizados para úlceras crónicas de pie diabético |
| dc.creator.fl_str_mv |
Mateus Suárez, Sofia Valentina Torres Pinzón, Michelle María |
| dc.contributor.advisor.none.fl_str_mv |
Becerra Bayona, Silvia Milena Solarte David, Víctor Alfonso |
| dc.contributor.author.none.fl_str_mv |
Mateus Suárez, Sofia Valentina Torres Pinzón, Michelle María |
| dc.contributor.cvlac.spa.fl_str_mv |
Becerra Bayona, Silvia Milena [0001568861] Solarte David, Víctor Alfonso [0001329391] |
| dc.contributor.googlescholar.spa.fl_str_mv |
Becerra Bayona, Silvia Milena [5wr21EQAAAAJ&hl=es&oi=ao] |
| dc.contributor.orcid.spa.fl_str_mv |
Becerra Bayona, Silvia Milena [0000-0002-4499-5885] Solarte David, Víctor Alfonso [0000-0002-9856-1484] |
| dc.contributor.scopus.none.fl_str_mv |
Becerra Bayona, Silvia Milena [36522328100] |
| dc.contributor.researchgate.spa.fl_str_mv |
Becerra Bayona, Silvia Milena [Silvia-Becerra-Bayona] Solarte David, Víctor Alfonso [Victor-Solarte-David] |
| dc.contributor.apolounab.none.fl_str_mv |
Becerra Bayona, Silvia Milena [silvia-milena-becerra-bayona] |
| dc.contributor.linkedin.none.fl_str_mv |
Becerra Bayona, Silvia Milena [silvia-becerra-3174455a] |
| dc.subject.keywords.spa.fl_str_mv |
Biomedical engineering Engineering Medical electronics Biological physics Bioengineering Medical instruments and apparatus Medicine Pegda 3D bioprinting Biomaterial ink CDFU Foot diseases Biomolecules |
| topic |
Biomedical engineering Engineering Medical electronics Biological physics Bioengineering Medical instruments and apparatus Medicine Pegda 3D bioprinting Biomaterial ink CDFU Foot diseases Biomolecules Ingeniería biomédica Ingeniería Biofísica Bioingeniería Medicina Enfermedades de los pies Biomoléculas Ingeniería clínica Clinical engineering Electrónica médica Instrumentos y aparatos médicos Pegda Bioimpresión 3D Tinta de biomaterial PRP UCPD |
| dc.subject.lemb.spa.fl_str_mv |
Ingeniería biomédica Ingeniería Biofísica Bioingeniería Medicina Enfermedades de los pies Biomoléculas |
| dc.subject.proposal.spa.fl_str_mv |
Ingeniería clínica Clinical engineering Electrónica médica Instrumentos y aparatos médicos Pegda Bioimpresión 3D Tinta de biomaterial PRP UCPD |
| description |
Las úlceras crónicas de pie diabético (UCPD) son una problemática que afecta la integridad de la piel, la cual necesita de una matriz extracelular (andamio) y biomoléculas para lograr el proceso cicatrización. Las biomoléculas inmersas en el plasma rico en plaquetas (PRP), incluyen factores de crecimiento que contribuyen a la regeneración de tejidos, por lo que se propuso el diseño de una tinta de biomaterial de polietilenglicol diacrilato (PEGDA) y PRP para potenciales aplicaciones en el desarrollo de apósitos personalizados, como tratamiento alternativo para promover la cicatrización de UCPD. El estudio planteo la búsqueda de un material viscoso (ThA) para aumentar la imprimibilidad del polímero, la inmovilización del PRP en la tinta de PEGDA al 10, 20 y 30% p/v, y ThA, y la evaluación de la imprimibilidad al variar los parámetros de flujo (150, 250 y 350%) y velocidad de extrusión (2 y 5 mm/s). Por lo anterior, se empleó gelatina para permitir la impresión de la mezcla, y utilizarla como una matriz de sacrificio que fuera liberada de la estructura. Así mismo se obtuvieron tintas de biomaterial con una óptima imprimibilidad según la fidelidad en la morfología y dimensiones diseñadas, con una formación de filamentos continuos. Posteriormente, se determinó que el PRP no es apto para la extrusión de un filamento y no permite la obtención de una solución homogénea al ser mezclado con la tinta de biomaterial, por lo que, basado en nuestro criterio, no puede ser utilizado para impresión. Con base en lo anterior, se establece que la tinta tiene potencial de ser usada para la inmovilización de biomoléculas y mejorar el tratamiento de las UCPD, al permitir la fabricación de andamios personalizados. |
| publishDate |
2021 |
| dc.date.accessioned.none.fl_str_mv |
2021-08-12T13:53:24Z |
| dc.date.available.none.fl_str_mv |
2021-08-12T13:53:24Z |
| dc.date.issued.none.fl_str_mv |
2021 |
| dc.type.driver.none.fl_str_mv |
info:eu-repo/semantics/bachelorThesis |
| dc.type.local.spa.fl_str_mv |
Trabajo de Grado |
| dc.type.coar.none.fl_str_mv |
http://purl.org/coar/resource_type/c_7a1f |
| dc.type.redcol.none.fl_str_mv |
http://purl.org/redcol/resource_type/TP |
| format |
http://purl.org/coar/resource_type/c_7a1f |
| dc.identifier.uri.none.fl_str_mv |
http://hdl.handle.net/20.500.12749/13790 |
| dc.identifier.instname.spa.fl_str_mv |
instname:Universidad Autónoma de Bucaramanga - UNAB |
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reponame:Repositorio Institucional UNAB |
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repourl:https://repository.unab.edu.co |
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http://hdl.handle.net/20.500.12749/13790 |
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instname:Universidad Autónoma de Bucaramanga - UNAB reponame:Repositorio Institucional UNAB repourl:https://repository.unab.edu.co |
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spa |
| language |
spa |
| dc.relation.references.spa.fl_str_mv |
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Acta biomaterialia. doi:10.1016/j.actbio.2019.01.039 Somasekharan, L. T., Kasoju, N., Raju, R., & Bhatt, A. (2020). Formulation and Characterization of Alginate Dialdehyde, Gelatin, and Platelet-Rich Plasma-Based Bioink for Bioprinting Applications. Bioengineering (Basel, Switzerland). doi:10.3390/bioengineering7030108 Tan, C. T., Liang, K., Ngo, Z. H., Dube, C. T., & Lim, C. Y. (2020). Application of 3D Bioprinting Technologies to the Management and Treatment of Diabetic Foot Ulcers. Biomedicines. doi:https://doi.org/10.3390/biomedicines8100441 Tan, C. T., Liang, K., Ngo, Z. H., Dube, C. T., & Lim, C. Y. (2020). Application of 3D Bioprinting Technologies to the Management and Treatment of Diabetic Foot Ulcers. Biomedicines, 8. doi:https://doi.org/10.3390/biomedicines8100441 Tan, F., Xu, X., Deng, T., Yin, M., Zhang, X., & Wang, J. (2012). Fabrication of positively charged poly(ethylene glycol)-diacrylate hydrogel as a bone tissue engineering scaffold. Biomedical materials. doi:https://doi.org/10.1088/1748-6041/7/5/055009 Uccioli, L., Izzo, V., Meloni, M., Vainieri, E., Ruotolo, V., & Giurato, L. (2015). Non-healing foot ulcers in diabetic patients: general and local interfering conditions and management options with advanced wound dressings. Journal of wound care. doi:10.12968/jowc.2015.24.Sup4b.35 Williams, D., Thayer, P., Martinez, H., Gatenholm, E., & Khademhosseini, A. (2018). A Perspective on the Physical, Mechanical and Biological Specifications of Bioinks and the Development of Functional Tissues in 3D Bioprinting. Bioprinting. doi:https://doi.org/10.1016/j.bprint.2018.02.003 Yang , J., Olanrele, O., Zhang, X., & Hsu, C. (2018). Fabrication of Hydrogel Materials for Biomedical Applications. Advances in experimental medicine and biology. doi:10.1007/978-981-13-0947-2_12 Zhang, B., Cristescu, R., Chrisey, D., & Narayan, R. (2020). Solvent-based Extrusion 3D Printing for the Fabrication of Tissue Engineering Scaffolds. International journal of bioprinting. doi:10.18063/ijb.v6i1.211 Zhang, X., Yang, D., & Nie, J. (2008). Chitosan/polyethylene glycol diacrylate films as potential. International journal of biological macromolecules Zhang, Z., Jin, Y., Yin, J., Xu, C., Xiong, R., Christensen, K., . . . Ringeisen, B. (2018). Evaluation of bioink printability for bioprinting applications. Applied Physics Reviews. doi:https://doi.org/10.1063/1.5053979 |
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Becerra Bayona, Silvia Milenaf59fde3b-924f-4fcc-96e9-5fd6250b2daeSolarte David, Víctor Alfonso54590e96-eda3-4b43-9ffa-14bd35ed7d08Mateus Suárez, Sofia Valentina87389606-c1e8-4250-8635-02bd8f322ad4Torres Pinzón, Michelle María41e3113e-eab7-4fec-bc88-cc7c3efcd5edBecerra Bayona, Silvia Milena [0001568861]Solarte David, Víctor Alfonso [0001329391]Becerra Bayona, Silvia Milena [5wr21EQAAAAJ&hl=es&oi=ao]Becerra Bayona, Silvia Milena [0000-0002-4499-5885]Solarte David, Víctor Alfonso [0000-0002-9856-1484]Becerra Bayona, Silvia Milena [36522328100]Becerra Bayona, Silvia Milena [Silvia-Becerra-Bayona]Solarte David, Víctor Alfonso [Victor-Solarte-David]Becerra Bayona, Silvia Milena [silvia-milena-becerra-bayona]Becerra Bayona, Silvia Milena [silvia-becerra-3174455a]ColombiaUNAB Campus Bucaramanga2021-08-12T13:53:24Z2021-08-12T13:53:24Z2021http://hdl.handle.net/20.500.12749/13790instname:Universidad Autónoma de Bucaramanga - UNABreponame:Repositorio Institucional UNABrepourl:https://repository.unab.edu.coLas úlceras crónicas de pie diabético (UCPD) son una problemática que afecta la integridad de la piel, la cual necesita de una matriz extracelular (andamio) y biomoléculas para lograr el proceso cicatrización. Las biomoléculas inmersas en el plasma rico en plaquetas (PRP), incluyen factores de crecimiento que contribuyen a la regeneración de tejidos, por lo que se propuso el diseño de una tinta de biomaterial de polietilenglicol diacrilato (PEGDA) y PRP para potenciales aplicaciones en el desarrollo de apósitos personalizados, como tratamiento alternativo para promover la cicatrización de UCPD. El estudio planteo la búsqueda de un material viscoso (ThA) para aumentar la imprimibilidad del polímero, la inmovilización del PRP en la tinta de PEGDA al 10, 20 y 30% p/v, y ThA, y la evaluación de la imprimibilidad al variar los parámetros de flujo (150, 250 y 350%) y velocidad de extrusión (2 y 5 mm/s). Por lo anterior, se empleó gelatina para permitir la impresión de la mezcla, y utilizarla como una matriz de sacrificio que fuera liberada de la estructura. Así mismo se obtuvieron tintas de biomaterial con una óptima imprimibilidad según la fidelidad en la morfología y dimensiones diseñadas, con una formación de filamentos continuos. Posteriormente, se determinó que el PRP no es apto para la extrusión de un filamento y no permite la obtención de una solución homogénea al ser mezclado con la tinta de biomaterial, por lo que, basado en nuestro criterio, no puede ser utilizado para impresión. Con base en lo anterior, se establece que la tinta tiene potencial de ser usada para la inmovilización de biomoléculas y mejorar el tratamiento de las UCPD, al permitir la fabricación de andamios personalizados.Capítulo 1. Problema u oportunidad ................................................................................................ 9 1.1 Introducción ............................................................................................................................ 9 1.2 Planteamiento del problema ................................................................................................... 9 1.3 Justificación .......................................................................................................................... 11 1.4 Pregunta Problema ................................................................................................................ 12 1.5 Objetivo General ................................................................................................................... 12 1.6 Objetivos Especificas ........................................................................................................... 12 1.7 Limitaciones y delimitaciones .............................................................................................. 13 Capítulo 2. Marco Teórico ............................................................................................................. 14 2.1 Úlceras crónicas de pie diabético y su proceso de cicatrización .......................................... 14 2.2 Los apósitos como alternativa terapéutica a las UCPD ........................................................ 15 2.2.1 Hidrogeles y el polímero PEGDA .................................................................................. 15 2.2.2 Biomoléculas y el Plasma Rico en Plaquetas ................................................................ 16 2.3 La bioimpresión y sus principales características ................................................................. 18 2.3.1 Tinta de biomaterial ....................................................................................................... 18 2.3.2 Características de imprimibilidad y los parámetros de impresión................................ 19 Capítulo 3. Estado del Arte ............................................................................................................ 23 Capítulo 4. Metodología ................................................................................................................. 28 4.1 Pruebas preliminares de viscosidad para la tinta .................................................................. 28 4.3 Fabricación de hidrogeles y estudio preliminar de liberación de gelatina ........................... 30 4.4 Caracterización mecánica preliminar de los hidrogeles ....................................................... 31 4.5 Impresión de los hidrogeles usando la tinta de biomaterial .................................................. 32 4.6 Evaluación de la velocidad y flujo de impresión según parámetros de imprimibilidad ....... 33 4.7 Estudio preliminar de liberación de gelatina en impresiones ............................................... 34 4.8 Análisis estadísticos .............................................................................................................. 34 Capítulo 5. Resultados y Análisis de resultados ............................................................................ 36 5.1 Resultados ............................................................................................................................. 36 5.1.1 Pruebas preliminares de viscosidad para la tinta ........................................................... 36 5.1.2 Preparación de la tinta de biomaterial ............................................................................ 39 5.1.3 Estudio preliminar de liberación de gelatina: Hidrogeles .............................................. 41 5.1.4 Caracterización mecánica preliminar de los hidrogeles ................................................. 42 5.1.5 Impresiones de los hidrogeles a partir de la tinta de biomaterial ................................... 44 5.1.5.1 Estandarización preliminar de las condiciones de impresión de la tinta de gelatina. ............................................................................................................................................. 46 5.1.5.2 Estandarización preliminar de las condiciones de impresión de la tinta de biomaterial de PEGDA y gelatina ....................................................................................... 49 5.1.6 Estudio preliminar de liberación de gelatina: Impresiones ............................................ 54 5.1.7 Preparación de la tinta de biomaterial con PRP ............................................................. 55 5.2. Análisis de Resultados ......................................................................................................... 56 Capítulo 6: Conclusiones y recomendaciones ................................................................................ 63 Referencias ..................................................................................................................................... 65PregradoChronic diabetic foot ulcers (UCPD) are a problem that affects the integrity of the skin, which needs an extracellular matrix (scaffold) and biomolecules to achieve the healing process. Biomolecules immersed in platelet-rich plasma (PRP) include growth factors that contribute to tissue regeneration, which is why the design of a polyethylene glycol diacrylate (PEGDA) and PRP biomaterial ink was proposed for potential applications in the development of personalized dressings, as an alternative treatment to promote the healing of UCPD. The study proposed the search for a viscous material (ThA) to increase the printability of the polymer, the immobilization of PRP in the PEGDA ink at 10, 20 and 30% w / v, and ThA, and the evaluation of the printability by varying the flow parameters (150, 250 and 350%) and extrusion speed (2 and 5 mm / s). Therefore, gelatin was used to allow the impression of the mixture, and use it as a sacrificial matrix that was released from the structure. Likewise, biomaterial inks were obtained with optimal printability according to the fidelity in the morphology and designed dimensions, with a formation of continuous filaments. Subsequently, it was determined that PRP is not suitable for the extrusion of a filament and does not allow obtaining a homogeneous solution when mixed with the biomaterial ink, therefore, based on our criteria, it cannot be used for printing. Based on the foregoing, it is established that the ink has the potential to be used for the immobilization of biomolecules and improve the treatment of UCPD, by allowing the manufacture of customized scaffolds.Modalidad Presencialapplication/pdfspahttp://creativecommons.org/licenses/by-nc-nd/2.5/co/Abierto (Texto Completo)info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Atribución-NoComercial-SinDerivadas 2.5 ColombiaDiseño de una tinta de biomaterial a base de pegda y plasma rico en plaquetas para potenciales aplicaciones en el desarrollo de apósitos personalizados para úlceras crónicas de pie diabéticoDesign of a pegda-based biomaterial ink and platelet-rich plasma for potential applications in the development of personalized dressings for chronic diabetic foot ulcersIngeniero BiomédicoUniversidad Autónoma de Bucaramanga UNABFacultad IngenieríaPregrado Ingeniería Biomédicainfo:eu-repo/semantics/bachelorThesisTrabajo de Gradohttp://purl.org/coar/resource_type/c_7a1fhttp://purl.org/redcol/resource_type/TPBiomedical engineeringEngineeringMedical electronicsBiological physicsBioengineeringMedical instruments and apparatusMedicinePegda3D bioprintingBiomaterial inkCDFUFoot diseasesBiomoleculesIngeniería biomédicaIngenieríaBiofísicaBioingenieríaMedicinaEnfermedades de los piesBiomoléculasIngeniería clínicaClinical engineeringElectrónica médicaInstrumentos y aparatos médicosPegdaBioimpresión 3DTinta de biomaterialPRPUCPDAlavi , A., Sibbald, R., Mayer, D., Goodman, L., Botros, M., Armstrong, D., . . . 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Applied Physics Reviews. doi:https://doi.org/10.1063/1.5053979ORIGINAL2021_Tesis_Michelle_Torres_Sofia_Mateus.pdf2021_Tesis_Michelle_Torres_Sofia_Mateus.pdfTesisapplication/pdf1902337https://repository.unab.edu.co/bitstream/20.500.12749/13790/1/2021_Tesis_Michelle_Torres_Sofia_Mateus.pdf2d26a9c96ce7d03cc94ea206e75d4011MD51open access2021_Licencia_Michelle_Torres.pdf2021_Licencia_Michelle_Torres.pdfLicenciaapplication/pdf1064014https://repository.unab.edu.co/bitstream/20.500.12749/13790/2/2021_Licencia_Michelle_Torres.pdf752cf97004813f0b0b1e8a4c6779f283MD52metadata only accessLICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://repository.unab.edu.co/bitstream/20.500.12749/13790/3/license.txt8a4605be74aa9ea9d79846c1fba20a33MD53open accessTHUMBNAIL2021_Tesis_Michelle_Torres_Sofia_Mateus.pdf.jpg2021_Tesis_Michelle_Torres_Sofia_Mateus.pdf.jpgIM Thumbnailimage/jpeg5398https://repository.unab.edu.co/bitstream/20.500.12749/13790/4/2021_Tesis_Michelle_Torres_Sofia_Mateus.pdf.jpg78fca079c318f5ddc9259ef92d6bb125MD54open access2021_Licencia_Michelle_Torres.pdf.jpg2021_Licencia_Michelle_Torres.pdf.jpgIM Thumbnailimage/jpeg10098https://repository.unab.edu.co/bitstream/20.500.12749/13790/5/2021_Licencia_Michelle_Torres.pdf.jpg70b6729c9b9190faf8399e1060b93317MD55metadata only access20.500.12749/13790oai:repository.unab.edu.co:20.500.12749/137902023-11-25 03:44:42.505open accessRepositorio Institucional | Universidad Autónoma de Bucaramanga - UNABrepositorio@unab.edu.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 |