Síntesis y Caracterización de Hidroxiapatita Sintética para la Preparación de Filmes de PLGA/HAp con Potencial Uso en Aplicaciones Biomédicas - Synthesis and Characterization of Synthetic Hydroxyapatite for the Preparation of PLGA/HAp Films with a Potential Use in Biomedical Applications
DOI:
https://doi.org/10.32870/recibe.v7i2.94Keywords:
Fracturas óseas, Filmes, PLGA/HAp, Caracterización fisicoquímica.Abstract
Los implantes de fijación de fracturas se emplean para resolver una fractura de hueso, actualmente hay una variedad de dispositivos como: agujas intramedulares, tachuelas y tornillos metálicos. Su función es estabilizar fragmentos de hueso en su sitio correcto durante su reparación ósea, para lograr una vascularización temprana. El objetivo de este estudio es sintetizar y caracterizar fisicoquímicamente hidroxiapatita sintética para fabricar filmes de PLGA 50:50/HAp. Se utilizó la técnica de espectroscopia infrarroja transformada de Fourier (FTIR) para buscar grupos funcionales principales. El análisis termogravimétrico (TGA) y la calorimetría diferencial de barrido (DSC) para evaluar el comportamiento de los filmes con respecto a la temperatura y caracterizar la superficie con microscopia electrónica de barrido (SEM). El espectro FTIR presenta señales de gran interés: se observa la zona aromática entre 1600 cm-1-1400 cm-1, señal característica de los aldehídos aromáticos(C=O) a los 1700 cm-1, alquenos aromáticos (C=O) a los 1300 cm-1 con traslapes de señales –C-H, =C-H, adicional una cuarta señal muy ancha entre los 3400-2400cm-1 asignada a –OH. Las micrografías de SEM, presentan homogeneidad en la superficie. El termograma TGA, se observa una pérdida de material a los 180°C del 5% aproximadamente y otro a 252°C del 10%. Finalmente, el termograma DSC, se observa alrededor de los 50 a 70°C, un ligero y amplio cambio nos permite creer que esa es la zona de transición vítrea del material, además se encontró un pico alrededor de los 52.07°C, donde se propone que ocurre la degradación de la formulación. Como trabajo futuro se realizarán pruebas de biocompatibilidad y degradación. Palabras clave: Fracturas óseas; Filmes; PLGA/HAp; Caracterización físicoquímica. Abstract: Fracture fixation implants are used to resolve a bone fracture, currently; there are a variety of devices such as intramedullary needles, tacks and, metal screws. Its function is to stabilize bone fragments in their correct place during their bone repair, to achieve an early vascularization. The objective of this study is to synthesize and physiochemically characterize of synthetic hydroxyapatite for the manufacturing of PLGA 50: 50 / Hap films. Through the Fourier transform infrared spectroscopy technique (FTIR) to look for main functional groups. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) to evaluate the behavior of films with respect to temperature and characterize the surface with scanning electron microscopy (SEM). The FTIR spectrum shows signs of great interest: the aromatic zone is observed between 1600 cm-1-1400 cm-1, characteristic signal of the aromatic aldehydes (C = O) at 1700 cm-1, aromatic alkenes (C = O) at 1300 cm-1 with overlapping signals -CH, = CH, additional a fourth signal very wide between 3400-2400cm-1 assigned to -OH. SEM micrographs show homogeneity on the surface. The TGA thermogram, a material loss is observed at 180 ° C of approximately 5% and another at 252 °C of 10%. Finally, the DSC thermogram is observed around 50 to 70 °C, a slight and wide change allows us to believe that this is the glass transition zone of the material, and a peak was found around 52.07 °C, where proposes that the degradation of the formulation occurs. As future work, biocompatibility and degradation tests will be carried out. Key words: Bone fractures; Films; PLGA/HAp; Physicochemical characterization.References
Agougui H., Aissa A., Maggi S., Debbabi M., (2010). Phosponate-hydroxyapatite hybrid componds prepared by hydrothermal method. Applied Surface Science, 257, 1377—1382.
Alimohammadi S., Salehi R., Amini N., Davaran S. (2012). Synthesis and physicochemical characterization of biodegradable PLGA-based Magnetic Nanoparticles Containing Amoxicilin; Biodegradable Nanoparticles containing amoxicillin. Bulletin of the Korean Chemical Society, 33, 3225-3232. 10.5012/bkcs.2012.33.10.3225.
Álvarez-Suarez A., López-Maldonado E., Graeve O., Martínez-Pallares F., Gómez-Pineda L.E., Oropeza-Guzmán M.E., Iglesias A.L., Ng T., Serena-Gómez E., Villarreal-Gómez L.J. (2017). Fabrication of porous polymeric structures using a simple sonication technique for tissue engineering. Journal of Polymer Engineering, 37(9): 943-951. doi:10.1515/polyeng-2016-0423.
Blanco M.D., Sastre R.L., Teijón C., Olmo R., Teijón J.M. (2005). 5-Fluorouracil-loaded microspheres prepared by spray-drying poly (D, L-lactide) and poly(lactide-co-glycolide) polymers: characterization and drug release. Journal of Microencapsulation, 22, 671-682. doi: 10.1080/02652040500161990.
Biazar E., Heidari M., Asefnezhad A., Montazeri N. (2011). The relationship between cellular adhesion and surface roughness in polystyrene modified by microwave plasma radiation. International Journal of Nanomedicine. 6, 631-639. doi:10.2147/IJN.S17218.
Carvalho E., Alves, C.D., Magalhães R. J., De Souza F., De Sousa F.R., Geraldo S. R. (2012). Synthesis and Characterization of Poly (D, L-Lactide-co-Glycolide) Copolymer. Journal of Biomaterials and Nanobiotechnology, 3, 208-225. doi: 10.4236/jbnb.2012.32027.
Cecen B., Kozaki L.D., Yuksel M., Ustun O, Ergur B.U., Havitcioglu H. (2016). Biocompatibility and biomechanical characteristics of loofah based scaffolds combined with hydroxyapatite, cellulose, poly-L-lactid acid with chondrocyte-like cells. Materials Science and Engineering C. 69, 437-446. doi:10.1016/j.msec.2016.07.007.
Cegnar M., Premzl A., Zavasnik B.V., Kristl J., Kos J., (2004). Poly(lactide-co-glycolide) nanoparticles as a carrier system for delivering cysteine protease inhibitor cystatin into tumor cells. Experimental Cell Research, 301, 223-231. Doi: 10.1016/j.yexcr.2004.07.021.
Chang H-I and Wang Y. (August 29th 2011). Cell Responses to Surface and Architecture of Tissue Engineering Scaffolds, Regenerative Medicine and Tissue Engineering Daniel Eberli, IntechOpen, DOI: 10.5772/21983.
D’Avila C.E., Alves, R.J., Resende, J.M., de Souza Freitas R.F., de Sousa, R.G. (2012). Synthesis and Characterization of Poly (D, L-Lactide-co-Glycolide) Copolymer. Journal of Biomaterials and Nanobiotechnology, 3, 208-225. doi: 10.4236/jbnb.2012.32027.
Da Cunha M.R., Gushiken V.O., Mardegan Issa J.P., Iatecola A., Pettian M., Santos A.R. Jr. (2011). Osteoconductive Capacity of Hydroxyapatite Implanted into the Skull of Diabetics. Journal of Craniofacial Surgery. 22(6): 2048–2052, DOI: 10.1097/SCS.0b013e3182319876.
Danhier, F., Ansorena, E., Silva, J.M., Coco, R., Le Breton, A., Préat, V. (2012). PLGA-based nanoparticles: An overview of biomedical applications. Journal of Controlled Release,161, 505-522. doi: 10.1016/j.jconrel.2012.01.043.
Davachi S.M., Kaffasi B., Roushanded J.M., Torabinejad B. (2012). Investigating thermal degradation, crystallization and surface behavior of L-lactide, glycolide and trimethylene carbonate terpolymers used for medical applications. Materials Science and Engineering C, 32, 98-104. doi.org/10.1016/j.msec.2011.10.001.
Dong Y., Feng S.S., (2005). Poly (D, L-lactide-co-glycolide)/montmorillonite nanoparticles for oral delivery of anticancer drugs. Biomaterials, 26, 6068-6076. doi: 10.1016/j.biomaterials.2005.03.021.
Douglas T., Pamula E., Hauk D., Wiltfang J., Sivananthan S., Sherry E., Warnke P.H. (2009). Porous polymer/hydroxyapatite scaffolds: characterization and biocompatibility investigations. Journal of Materials Science: Materials in Medicine, 20 (9), 1909-1915. doi: 10.1007/s10856-009-3756-7. Epub 2009 May 5.
Durucan C., Brown P. W. (2001). Biodegradable hydroxyapatite–polymer composites. Advanced Engineering Materials, 3(4), 227-231.
Gasami H., Siepmann F., Hamoudi M.C., Danede F., Verin J., Williart J.F. Siepmann J. (2016). Towards a better understanding of the different release phases from PLGA microparticles: Dexamethasone-Loaded systems. International Journal of Pharmaceutics. 514, 186-199. doi: 10.1016/j.ijpharm.2016.08.032.
Gasmi H., Williart J.F., Danede F., Hamoudi M.C., Siepmann J., Siepmann F. (2015). Importance of PLGA microparticle swelling for the control of prilocaine release. Journal of Drug Delivery Science and Technology, 30, 123-132. doi: 10.1016/j.jddst.2015.10.009.
Hausberg A.G., De Luca P.P. (1995). Characterization of biodegradable poly (DL-lactide-co-glycolide) polymers and microspheres. Journal of pharmaceutical & biomedical analysis, 13 (6), 747-760. doi: doi.org/10.1016/0731-7085(95)01276-Q.
Higuita L.P., Vargas A.F., Gil M.J., Giraldo L.F. (2016). Synthesis and characterization of nanocomposite based on hydroxyapatite and monetite. Materials Letters, 175, 169-172. doi.org/10.1016/j.matlet.2016.04.011.
Hu X., Park S-H., Gil E.S., Xia X-X., Weiss A.S., Kaplan D.L. (2011). The Influence of Elasticity and Surface Roughness on Myogenic and Osteogenic-Differentiation of Cells on Silk-Elastin Biomaterials. Biomaterials, 32 (34), 8979-8989. doi:10.1016/j.biomaterials.2011.08.037.
Hu X., Shen H., Yang F., Liang X., Wang S., Wu D. (2014). Modified composite microspheres of hydroxyapatite and poly(lactide-co-glycolide) as an injectable scaffold. Applied Surface Science, 292, 764-772. doi.org/10.1016/j.apsusc.2013.12.045.
Hughes J.M., Nekvasil H., Ustunisik G., Lindsley D.H., Coraor A.E., Vaughn J., Phillips B.L., McCubbin F.M., Woerner W.R. (2014). Solid solution in the fluorapatite-chlorapatite binary system: High-precision crystal structure refinements of synthetic F-Cl apatite, American Mineralogist, 99, 369-376.
Jebri S., Khattech I., Jemal M. (2017). Standard enthalpy, entropy and Gibbs free energy of formation of “A” type carbonate phosphocalcium hydroxyapatites. The Journal of Chemical Thermodynamics, 106, 84-94.
Khan W.S., Rayan F., Dhinsa B.S., Marsh D. (2012). An Osteoconductive, Osteoinductive, and Osteogenic Tissue-Engineered Product for Trauma and Orthopaedic Surgery: How Far Are We?, Stem Cells International, 2012, Article ID 236231, https://doi.org/10.1155/2012/236231.
Lee J.B., Lee S.H., Yu S.M., Park J.C., Choi J.B., Kim J.K. (2008). PLGA scaffold incorporated with hydroxyapatite for cartilage regeneration. Surface and Coatings Technology, 202, 5757-5761. doi.org/10.1016/j.surfcoat.2008.06.138.
Liuyun J. Chengdong, Lixin J., Lijuan X. (2014). Effect of hydroxyapatite with different morphology on the crystallization behavior, mechanical property and in vitro degradation of hydroxyapatite/poly(lactic-co-glycolic) composite. Composites Science and Technology, 93, 61-67. doi.org/10.1016/j.compscitech.2013.12.026.
Maheshwari S.U. S., Samuel VK., Nagiah N. (2014). Fabrication and evaluation of (PVA/HAp/PCL) bilayer composites as potential scaffolds for bone tissue regeneration application. Ceramics International, 40, 8469-8477. doi.org/10.1016/j.ceramint.2014.01.058.
Maitz M.F. (2015). Applications of synthetic polymers in clinical medicine. Journal Biosurface and Biotribology, 1, 161-176. doi: 10.1016/j.bsbt.2015.08.002.
Mehrasa M., Asadollahi M.A., Ghaedi K., Salehi H., Arpanaei A. (2015). Electrospun aligned PLGA and PLGA/gelatin nanofibers embedded with silica nanoparticles for tissue engineering.
International Journal of Biological Macromolecules, 79, 687-695. doi.org/10.1016/j.ijbiomac.2015.05.050.
Mehrasa M., Asadollahi M.A., Nasri-Nasrabadi B., Ghaedi K., Salehi H., Dolatshahi Pirouz A., Arpanaei A. (2016). Incorporation of mesoporous silica nanoparticles into random electrospun PLGA and PLGA/gelatin nanofibrous scaffolds enhances mechanical and cell proliferation properties. Materials Science and Engineering: C, 66, 25-32. doi.org/10.1016/j.msec.2016.04.031.
Naik A., Best S.M., Cameron R.E. (2015). The influence of silanisation on the mechanical and degradation behaviour of PLGA/HA composites. Materials Science and Engineering: C, 8, 642-650. doi.org/10.1016/j.msec.2014.12.056.
Ngiam M., Liao S., Patil A.J., Cheng Z., Chan K.C., Ramakrishna S. (2009). The fabrication of nano-hydroxyapatite on PLGA and PLGA/collagen nanofibrous composite scaffolds and their effects in osteoblastic behavior for bone tissue engineering. Bone, 45, 4-16. doi.org/10.1016/j.bone.2009.03.674.
Oh J.H., Park K.M., Lee J.S., Moon H.T., Park K.D. (2012). Electrospun microfibrous PLGA meshes coated with in situ cross-linkable gelatin hydrogels for tissue regeneration. Current Applied Physics, 12, S144-S149. doi.org/10.1016/j.cap.2012.02.047.
Quian J., Xu W., Yong X., Jin X., Zhang W., (2014). Fabrication and in vitro biocompatibility of biomorphic PLGA/nHA composite scaffolds for bone tissue engineering. Materials Science and Engineering: C, 36, 95-101. doi.org/10.1016/j.msec.2013.11.047.
Rosas J., Pedraz J. (2007). Microesferas de PLGA: un sistema para la liberación controlada de moléculas con actividad inmunogenica. Revista Colombiana de Ciencias Químico-Farmacéuticas, 36 (2), 134-153. Doi: 10.15446/rcciquifa.
Sánchez A., Vera R., Muñoz E., Gomez E., Bernard M., Maciel A. (2016). Preparación y caracterización de membranas poliméricas electrohiladas de policaprolactona y quitosano para la liberación controlada de clorohidrato de tiamina. Ciencia en Desarrollo. 7 (2),133-151. doi.org/10.19053/01217488.v7.n2.2016.4818.
Sequeda, L., Díaz, J., Gutiérrez, S., Perdomo, S., Gómez, O. (2012). Obtención de hidroxiapatita sintética por tres métodos diferentes y su caracterización para ser utilizada como sustituto óseo. Revista Colombiana de Ciencias Químico Farmacéuticas, 41 (1), 50-60.
Soriano I., Évora C. (2000). Formulation of calcium phosphates /poly (d,l-lactide) blends containing gentamicin for bone implantation. Journal of Controlled Release, 68, 121-134. doi.org/10.1016/S0168-3659(00)00251-0.
Swetha M., Sahithi K., Moorthi A., Srinivasan N., Ramasamy K., Selvamurugan N. (2010). Biocomposites containing natural polymers and hydroxyapatite for bone tissue engineering. International Journal of Biological Macromolecules, 47 (1), 1-4. doi: 10.1016/j.ijbiomac.2010.03.015.
Thomas M., Arora A., Katti D. (2014). Surface hydrophilicity of PLGA fibers governs in vitro mineralization and osteogenic differentiation. Materials Science and Engineering: C, 45, 320-332. doi.org/10.1016/j.msec.2014.08.074.
Tukulula M., Hayeshi R., Fonteh P., Meyer D., Ndamase A., Madziva M.T., Khumalo V., Labuschagne P., Naicker B., Swai H., Dube A. (2015). Curdlan-Conjugated PLGA Nanoparticles Possess Macrophage Stimulant Activity and Drug Delivery Capabilities. Pharmaceutical Research, 32 (8): 2713-26. doi: 10.1007/s11095-015-1655-9.
Upson S., Partridge S.W., Tcacencu I., Fulton D.A., Corbett I., German M.J., Dalgarno K.W. (2016). Development of a methacrylate-terminated PLGA copolymer for potential use in craniomaxillofacial fracture plates. Materials Science and Engineering C, 69, 470-477. doi.org/10.1016/j.msec.2016.06.012.
Villarreal-Gómez L.J., Vera-Graziano R., Vega-Ríos M.R., Pineda-Camacho J.L., Mier-Maldonado P.A., Almanza-Reyes H., Cornejo Bravo J.M. (2014a). In Vivo Biocompatibility of Dental Scaffolds for Tissue Regeneration. Advanced Materials Research 06/2014; Chapter 3(Materials Applications). DOI: 10.4028/www.scientific.net/AMR.976.191 4.
Villarreal-Gómez L.J., Vera-Graziano R., Vega-Ríos M.R., Pineda-Camacho J.L., Mier-Maldonado P.A., Almanza-Reyes H., Cornejo Bravo J.M. (2014b). Biocompatibility Evaluation of Electrospun Scaffolds of Poly (L-Lactide) with Pure and Grafted Hydroxyapatite. Journal of the Mexican Chemical Society 10/2014, 2014(584).
Vukomanović M., Škapin S.D., Poljanšek I., Žagar E., Kralj B., Ignjatović N., Uskoković D. Poly(D, L-lactide-co-glycolide)/hydroxyapatite core–shell nanosphere. Part 2: Simultaneous release of a drug and a prodrug (clindamycin and clindamycin phosphate). Colloids and Surfaces B: Biointerfaces, 82 (2), 414-421. https://doi.org/10.1016/j.colsurfb.2010.09.012.
Xiao W., Fu H., Rahaman M.N., Liu Y., Bal B.S. (2013). Hollow hydroxyapatite microspheres: A novel bioactive and osteoconductive carrier for controlled release of bone morphogenetic protein-2 in bone regeneration, Acta Biomaterialia, 9 (9), 8374-8383. https://doi.org/10.1016/j.actbio.2013.05.029.
Xian, W. (2010). A laboratory Course in Biomaterials. CRC Press.
Yoo H.S., Lee K.H., Oh J.E., Park T.G. (2000). In vitro and in vivo anti-tumor activities of nanoparticles based on doxorubicin-PLGA conjugates. Journal of Controlled Release: Official Journal of the Controlled Release Society, 68 (3), 419-431. doi: 10.1016/S0168-3659(00)00280-7.
Zhao X., Han Y., Li J., Cai B., Gao H., Feng W., Li S., Liu J., Li D. (2017). BMP-2 immobilized PLGA/hydroxyapatite fibrous scaffold via polydopamine stimulates osteoblast growth. Materials Science and Engineering: C, 78, 658-666. doi.org/10.1016/j.msec.2017.03.186.