29 research outputs found

    The effect of salt fusion processing variables on structural, physicochemical and biological properties of poly(glycerol sebacate) scaffolds

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    "This is an Accepted Manuscript of an article published by Taylor & Francis in International Journal of Polymeric Materials and Polymeric Biomaterials on SEP 21 2020, available online: https://www.tandfonline.com/doi/full/10.1080/00914037.2019.1636247"[EN] Poly(glycerol sebacate), PGS, is a biodegradable elastomer recently proposed in the form of scaffolds for cardiac, vascular, cartilage or neural applications. In the present work, several processing variables for the fabrication of PGS scaffolds by the salt fusion method were systematically studied, namely the pre-polymer/porogen ratio, the salt particles average size, use of tetrahydrofuran to dissolve the pre-polymer for its injection in the porogen template, and the curing pressure. The effect of these variables on their structural, mechanical and biological properties was assessed to select those leading to optimal ones in terms of their potential performance in tissue engineering applications.The authors acknowledge Spanish Ministerio de Economia y Competitividad through DPI2015-65401-C3-2-R project. The authors acknowledge the assistance and advice of the Electron Microscopy Service of the Universitat Politecnica de Valencia (Spain).Vilariño, G.; Muñoz-Santa, A.; Conejero-Garcia, Á.; VallĂ©s Lluch, A. (2020). The effect of salt fusion processing variables on structural, physicochemical and biological properties of poly(glycerol sebacate) scaffolds. International Journal of Polymeric Materials. 69(14):938-945. https://doi.org/10.1080/00914037.2019.1636247S9389456914Fung, Y.-C. (1993). Bioviscoelastic Solids. Biomechanics, 242-320. doi:10.1007/978-1-4757-2257-4_7Chiang, B., Kim, Y. C., Doty, A. C., Grossniklaus, H. E., Schwendeman, S. P., & Prausnitz, M. R. (2016). Sustained reduction of intraocular pressure by supraciliary delivery of brimonidine-loaded poly(lactic acid) microspheres for the treatment of glaucoma. Journal of Controlled Release, 228, 48-57. doi:10.1016/j.jconrel.2016.02.041Appuhamillage, G. A., Reagan, J. C., Khorsandi, S., Davidson, J. R., Voit, W., & Smaldone, R. A. (2017). 3D printed remendable polylactic acid blends with uniform mechanical strength enabled by a dynamic Diels–Alder reaction. Polymer Chemistry, 8(13), 2087-2092. doi:10.1039/c7py00310bZhu, W., Masood, F., O’Brien, J., & Zhang, L. G. (2015). Highly aligned nanocomposite scaffolds by electrospinning and electrospraying for neural tissue regeneration. Nanomedicine: Nanotechnology, Biology and Medicine, 11(3), 693-704. doi:10.1016/j.nano.2014.12.001Gao, S., Guo, W., Chen, M., Yuan, Z., Wang, M., Zhang, Y., 
 Guo, Q. (2017). Fabrication and characterization of electrospun nanofibers composed of decellularized meniscus extracellular matrix and polycaprolactone for meniscus tissue engineering. Journal of Materials Chemistry B, 5(12), 2273-2285. doi:10.1039/c6tb03299kHu, X., Hu, T., Guan, G., Yu, S., Wu, Y., & Wang, L. (2017). Control of weft yarn or density improves biocompatibility of PET small diameter artificial blood vessels. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 106(3), 954-964. doi:10.1002/jbm.b.33909Recco, M. S., Floriano, A. C., Tada, D. B., Lemes, A. P., Lang, R., & Cristovan, F. H. (2016). Poly(3-hydroxybutyrate-co-valerate)/poly(3-thiophene ethyl acetate) blends as a electroactive biomaterial substrate for tissue engineering application. RSC Advances, 6(30), 25330-25338. doi:10.1039/c5ra26747aRibeiro Lopes, J., Azevedo dos Reis, R., & Almeida, L. E. (2016). Production and characterization of films containing poly(hydroxybutyrate) (PHB) blended with esterified alginate (ALG-e) and poly(ethylene glycol) (PEG). Journal of Applied Polymer Science, 134(1). doi:10.1002/app.44362Wang, Y., Ameer, G. A., Sheppard, B. J., & Langer, R. (2002). A tough biodegradable elastomer. Nature Biotechnology, 20(6), 602-606. doi:10.1038/nbt0602-602Nagata, M., Kiyotsukuri, T., Ibuki, H., Tsutsumi, N., & Sakai, W. (1996). Synthesis and enzymatic degradation of regular network aliphatic polyesters. Reactive and Functional Polymers, 30(1-3), 165-171. doi:10.1016/1381-5148(95)00107-7Radisic, M., Park, H., Chen, F., Salazar-Lazzaro, J. E., Wang, Y., Dennis, R., 
 Vunjak-Novakovic, G. (2006). Biomimetic Approach to Cardiac Tissue Engineering: Oxygen Carriers and Channeled Scaffolds. Tissue Engineering, 12(8), 2077-2091. doi:10.1089/ten.2006.12.2077Chen, Q.-Z., Bismarck, A., Hansen, U., Junaid, S., Tran, M. Q., Harding, S. E., 
 Boccaccini, A. R. (2008). Characterisation of a soft elastomer poly(glycerol sebacate) designed to match the mechanical properties of myocardial tissue. Biomaterials, 29(1), 47-57. doi:10.1016/j.biomaterials.2007.09.010Ravichandran, R., Venugopal, J. R., Sundarrajan, S., Mukherjee, S., & Ramakrishna, S. (2011). Poly(Glycerol Sebacate)/Gelatin Core/Shell Fibrous Structure for Regeneration of Myocardial Infarction. Tissue Engineering Part A, 17(9-10), 1363-1373. doi:10.1089/ten.tea.2010.0441Masoumi, N., Annabi, N., Assmann, A., Larson, B. L., Hjortnaes, J., Alemdar, N., 
 Khademhosseini, A. (2014). Tri-layered elastomeric scaffolds for engineering heart valve leaflets. Biomaterials, 35(27), 7774-7785. doi:10.1016/j.biomaterials.2014.04.039Masoumi, N., Jean, A., Zugates, J. T., Johnson, K. L., & Engelmayr, G. C. (2012). Laser microfabricated poly(glycerol sebacate) scaffolds for heart valve tissue engineering. Journal of Biomedical Materials Research Part A, 101A(1), 104-114. doi:10.1002/jbm.a.34305Motlagh, D., Yang, J., Lui, K. Y., Webb, A. R., & Ameer, G. A. (2006). Hemocompatibility evaluation of poly(glycerol-sebacate) in vitro for vascular tissue engineering. Biomaterials, 27(24), 4315-4324. doi:10.1016/j.biomaterials.2006.04.010Frydrych, M., RomĂĄn, S., MacNeil, S., & Chen, B. (2015). Biomimetic poly(glycerol sebacate)/poly(l-lactic acid) blend scaffolds for adipose tissue engineering. Acta Biomaterialia, 18, 40-49. doi:10.1016/j.actbio.2015.03.004SUNDBACK, C., SHYU, J., WANG, Y., FAQUIN, W., LANGER, R., VACANTI, J., & HADLOCK, T. (2005). Biocompatibility analysis of poly(glycerol sebacate) as a nerve guide material. Biomaterials, 26(27), 5454-5464. doi:10.1016/j.biomaterials.2005.02.004Deng, Y., Bi, X., Zhou, H., You, Z., Wang, Y., 
 Fan, X. (2014). Repair of critical-sized bone defects with anti-miR-31-expressing bone marrow stromal stem cells and poly(glycerol sebacate) scaffolds. European Cells and Materials, 27, 13-25. doi:10.22203/ecm.v027a02Zhao, X., Wu, Y., Du, Y., Chen, X., Lei, B., Xue, Y., & Ma, P. X. (2015). A highly bioactive and biodegradable poly(glycerol sebacate)–silica glass hybrid elastomer with tailored mechanical properties for bone tissue regeneration. Journal of Materials Chemistry B, 3(16), 3222-3233. doi:10.1039/c4tb01693aZaky, S. H., Lee, K. W., Gao, J., Jensen, A., Verdelis, K., Wang, Y., 
 Sfeir, C. (2017). Poly (glycerol sebacate) elastomer supports bone regeneration by its mechanical properties being closer to osteoid tissue rather than to mature bone. Acta Biomaterialia, 54, 95-106. doi:10.1016/j.actbio.2017.01.053Jeong, C. G., & Hollister, S. J. (2010). A comparison of the influence of material on in vitro cartilage tissue engineering with PCL, PGS, and POC 3D scaffold architecture seeded with chondrocytes. Biomaterials, 31(15), 4304-4312. doi:10.1016/j.biomaterials.2010.01.145Kemppainen, J. M., & Hollister, S. J. (2010). Tailoring the mechanical properties of 3D-designed poly(glycerol sebacate) scaffolds for cartilage applications. Journal of Biomedical Materials Research Part A, 94A(1), 9-18. doi:10.1002/jbm.a.32653Sant, S., Hwang, C. M., Lee, S.-H., & Khademhosseini, A. (2011). Hybrid PGS-PCL microfibrous scaffolds with improved mechanical and biological properties. Journal of Tissue Engineering and Regenerative Medicine, 5(4), 283-291. doi:10.1002/term.313Gao, J., Crapo, P. M., & Wang, Y. (2006). Macroporous Elastomeric Scaffolds with Extensive Micropores for Soft Tissue Engineering. Tissue Engineering, 12(4), 917-925. doi:10.1089/ten.2006.12.917Gibson, L. J., & Ashby, M. F. (1997). Cellular Solids. doi:10.1017/cbo9781139878326Maliger, R., Halley, P. J., & Cooper-White, J. J. (2012). Poly(glycerol-sebacate) bioelastomers-kinetics of step-growth reactions using Fourier Transform (FT)-Raman spectroscopy. Journal of Applied Polymer Science, 127(5), 3980-3986. doi:10.1002/app.37719Ifkovits, J. L., Padera, R. F., & Burdick, J. A. (2008). Biodegradable and radically polymerized elastomers with enhanced processing capabilities. Biomedical Materials, 3(3), 034104. doi:10.1088/1748-6041/3/3/034104Chen, Q.-Z., Ishii, H., Thouas, G. A., Lyon, A. R., Wright, J. S., Blaker, J. J., 
 Harding, S. E. (2010). An elastomeric patch derived from poly(glycerol sebacate) for delivery of embryonic stem cells to the heart. Biomaterials, 31(14), 3885-3893. doi:10.1016/j.biomaterials.2010.01.10

    Channeled polymeric scaffolds with polypeptide gel filling for lengthwise guidance of neural cells

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    CNS damages are often irreversible since neurons of the central nervous system are unable to regenerate after an injury. As a new strategy within the nervous system tissue engineering, multifunctional systems based on two different biomaterials to support axonal guidance in damaged connective tracts have been developed herein. These systems are composed of a channeled scaffold made of ethyl acrylate and hydroxyethyl acrylate copolymer, P(EA-co-HEA), with parallel tubular micropores, combined with an injectable and in situ gelable self-assembling polypeptide (RAD16-I) as pores filler. The polymer scaffold is intended to provide a three-dimensional context for axon growth; subsequently, its morphology and physicochemical parameters have been determined by scanning electron microscopy, density measurements and compression tests. Besides, the hydrogel acts as a cell-friendly nanoenvironment while it creates a gradient of bioactive molecules (nerve growth factor, NGF) along the scaffolds channels; the chemotactic effect of NGF has been evaluated by a quantitative ELISA assay. These multifunctional systems have shown ability to keep circulating NGF, as well as proper short-term in vitro biological response with glial cells and neural progenitors.The authors acknowledge funding through the Spanish Ministerio de Ciencia e Innovacion (MAT2011-28791-C03-02 and -03). Dr. J.M. Garcia Verdugo (Department of Comparative Neurobiology, Cavanilles Institute of Biodiversity and Evolutive Biology, Universitat de Valencia) is thanked for kindly providing the cells employed in this work.Conejero García, Á.; Vilarino-Feltrer, G.; Martínez Ramos, C.; Monleón Pradas, M.; Vallés Lluch, A. (2015). Channeled polymeric scaffolds with polypeptide gel filling for lengthwise guidance of neural cells. European Polymer Journal. 70:331-341. doi:10.1016/j.eurpolymj.2015.07.033S3313417

    Scaffolds based on hyaluronan and carbon nanotubes gels

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    [EN] Physico-chemical and mechanical properties of hyaluronic acid/carbon nanotubes nanohybrids have been correlated with the proportion of inorganic nanophase and the preparation procedure. The mass fraction of -COOH functionalized carbon nanotubes was varied from 0 to 0.05. Hyaluronic acid was crosslinked with divinyl sulfone to improve its stability in aqueous media and allow its handling as a hydrogel. A series of samples was dried by lyophilization to obtain porous scaffolds whereas another was room-dried allowing the collapse of the hybrid structures. The porosity of the former, together with the tighter packing of hyaluronic acid chains, results in a lower water absorption and lower mechanical properties in the swollen state, because of the easier water diffusion. The presence of even a small amount of carbon nanotubes (mass fraction of 0.05) limits even more the swelling of the matrix, owing probably to hybrid interactions. These nanohybrids do not seem to degrade significantly during 14 days in water or enzymatic medium.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Contract grant sponsor: Spanish Ministerio de Economia y Competitividad; contract grant numbers: MAT2011-28791-C03-02 and -03.Arnal Pastor, MP.; Tallà-Ferrer, C.; Herrero-Herrero, M.; Martínez-Gómez Aldaraví, A.; Monleón Pradas, M.; Vallés Lluch, A. (2016). Scaffolds based on hyaluronan and carbon nanotubes gels. Journal of Biomaterials Applications. 31(4):534-543. https://doi.org/10.1177/0885328216644535S53454331

    One-dimensional migration of olfactory ensheathing cells on synthetic materials: Experimental and numerical characterization

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    Olfactory ensheathing cells (OECs) are of great interest for regenerative purposes since they are believed to aid axonal growth. With the view set on the strategies to achieve reconnection between neuronal structures, it is of great importance to characterize the behaviour of these cells on long thread-like structures that may efficiently guide cell spread in a targeted way. Here, rat OECs were studied on polycaprolactone (PCL) long monofilaments, on long bars and on discs. PCL turns out to be an excellent substrate for OECs. The cells cover long distances along the monofilaments and colonize completely these struc- tures. With the help of a one-dimensional (1D) analytical model, a migration coefficient, a net proliferation rate constant and the fraction of all cells which undergo migration were obtained. The separate effect of the three phenomena summarized by these parameters on the colo- nization patterns of the 1D path was qualitatively dis- cussed. Other features of interest were also determined, such as the speed of the advance front of colonization and the order of the kinetics of net cell proliferation. Charac- terizing migration by means of these quantities may be useful for comparing and predicting features of the colo- nization process (such as times, patterns, advance fronts and proportion of motile cells) of different cell substrate combinations.Support of the Spanish Science & Innovation Ministery through project MAT2008-06434 is acknowledged. MMP and CMR acknowledge partial funding through the "Convenio de Colaboracion para la Investigacion Basica y Traslacional en Medicina Regenerativa" between the Instituto Nacional de Salud Carlos III, the Conselleria de Sanidad of the Generalitat Valenciana and the Foundation Centro de Investigacion Principe Felipe.Perez Garnes, M.; MartĂ­nez Ramos, C.; Barcia, JA.; Escobar Ivirico, JL.; Gomez Pinedo, UA.; VallĂ©s Lluch, A.; MonleĂłn Pradas, M. (2013). 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    Effect of an organotin catalyst on the physicochemical properties and biocompatibility of castor oil-based polyurethane/cellulose composites

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    [EN] Polyurethane/cellulose composites were synthesized from castor-oil-derived polyols and isophorone diisocyanate using dibutyltin dilaurate (DBTDL) as the catalyst. Materials were obtained by adding 2% cellulose in the form of either microcrystals (20 lm) or nanocrystals obtained by acid hydrolysis. The aim was to assess the effects of filler particle size and the use of a catalyst on the physicochemical properties and biological response of these composites. The addition of the catalyst was found to be essential to prevent filler aggregations and to enhance the tensile strength and elongation at break. The cellulose particle size influenced the composite properties, as its nanocrystals heighten hydrogen bond interactions between the filler surface and polyurethane domains, improving resistance to hydrolytic degradation. All hybrids retained cell viability, and the addition of DBTDL did not impair their biocompatibility. The samples were prone to calcification, which suggests that they could find application in the development of bioactive materials.Universidad de La Sabana supported this work under Grant No. ING-176-2016. S.V.V. acknowledges the Universidad de La Sabana for the Teaching Assistant Scholarship for his master's studies. J.A.G.T. and A.V.L. acknowledge the support of the Spanish Ministry of Economy and Competitiveness (MINECO) through project DPI2015-65401-C3-2-R (including FEDER financial support). The authors acknowledge the assistance and advice of the Electron Microscopy Service of the UPV. CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program. CIBER Actions are financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund.Villegas-Villalobos, S.; Diaz, L.; Vilariño, G.; VallĂ©s Lluch, A.; GĂłmez-Tejedor, J.; Valero, M. (2018). 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    Interaction between acrylic substrates and RAD16-I peptide in its self-assembling

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    [EN] Self-assembling peptides (SAP) are widely used as scaffolds themselves, and recently as fillers of microporous scaffolds, where the former provides a cell-friendly nanoenvironment and the latter improves its mechanical properties. The characterization of the interaction between these short peptides and the scaffold material is crucial to assess the potential of such a combined system. In this work, the interaction between poly(ethyl acrylate) (PEA) and 90/10 ethyl acrylate-acrylic acid copolymer P(EAcoAAc) with the SAP RAD16-I has been followed using a bidimensional simplified model. By means of the techniques of choice (congo red staining, atomic force microscopy (AFM), and contact angle measurements) the interaction and self-assembly of the peptide has proven to be very sensitive to the wettability and electro-negativity of the polymeric substrate.The authors acknowledge funding through the European Commission FP7 project RECATABI (NMP3-SL-2009-229239), and from the Spanish Ministerio de Ciencia e Innovacion through projects MAT2011-28791-C03-02 and -03. This work was also supported by the Spanish Ministerio de Educacion through M. Arnal-Pastor FPU 2009-1870 grant. The authors acknowledge the assistance and advice of Electron Microscopy Service of the UPV.Arnal Pastor, MP.; GonzĂĄlez-Mora, D.; GarcĂ­a-Torres, F.; MonleĂłn Pradas, M.; VallĂ©s Lluch, A. (2016). Interaction between acrylic substrates and RAD16-I peptide in its self-assembling. 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Differentiation 71:262–270Thonhoff JR, Lou DI, Jordan PM, Zhao X, Compatibility WP (2008) Of human fetal neural stem cells with hydrogel biomaterials in vitro. Brain Res 1187:42–51Tokunaga M, Liu ML, Nagai T, Iwanaga K, Matsuura K, Takahashi T, Kanda M, Kondo N, Wang P, Naito AT, Komuro I (2010) Implantation of cardiac progenitor cells using self-assembling peptide improves cardiac function after myocardial infarction. J Mol Cell Cardiol 49(6):972–983Takei J (2006) 3-Dimensional cell culture scaffold for everyone: drug screening. Tissue engineering and cancer biology. AATEX 11(3):170–176McGrath AM, Novikova LN, Novikov LN, Wiberg MBD (2010) ℱ PuraMatrixℱ peptide hydrogel seeded with Schwann cells for peripheral nerve regeneration. Brain Res Bull 83(5):207–213Wang W, Itoh S, Matsuda A, Aizawa T, Demura M, Ichinose S, Shinomiya K, Tanaka J (2008) Enhanced nerve regeneration through a bilayered chitosan tube: The effect ofintroduction of glycine spacer into the CYIGSR sequence. J Biomed Mater Res Part A 85:919–928Sargeant TD, Guler MO, Oppenheimer SM, Mata A, Satcher RL, Dunand DC, Stupp SI (2008) Hybrid bone implants: self-assembly of peptide amphiphile nanofibers within porous titanium. Biomaterials 29(2):161–171VallĂ©s-Lluch A, Arnal-Pastor M, MartĂ­nez-Ramos C, Vilariño-Feltrer G, Vikingsson L, Castells-Sala C, Semino CE, MonleĂłn Pradas M (2013) Combining self-assembling peptide gels with three-dimensional elastomer scaffolds. Acta Biomater 9(12):9451–9460Valles-Lluch A, Arnal-Pastor M, Martinez-Ramos C, Vilarino-Feltrer G, Vikingsson L, Monleon Pradas M (2013) Grid polymeric scaffolds with polypeptide gel filling as patches for infarcted tissue regeneration. 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    Electrospun adherent-antiadherent bilayered membranes based on cross-linked hyaluronic acid for advanced tissue engineering applications

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    [EN] A procedure to obtain electrospun mats of hyaluronic acid (HA) stable in aqueous media in one single step has been developed. It consists in combining an HA solution with a divinyl sulfone one as cross-linker in a three-way valve to immediately electroblow their mixture. Membranes obtained with this method, after sterilization and conditioning, are ready to use in cell culture without need of any additional posttreatment. HA nanofibers are deposited onto previously electrospun poly(L-lactic acid) (PLLA) mats in order to obtain stably joined bilayered membranes with an adherent face and the opposite face non-adherent, despite their different hydrophilicity and mechanical properties. These bilayered HA/PLLA membranes may be of use, for example, in applications seeking to transplant cells on a tissue surface and keep them protected from the environment: the PLLA nanofiber face is cell friendly and promotes cell attachment and spreading and can thus be used as a cell supply vehicle,. while the HA face hinders cell adhesion and thus may prevent post-surgical adherences, a major issue in many surgeries. (C) 2013 Elsevier B.V. All rights reserved.The authors acknowledge the financing through project FP7 NMP3-SL-2009-229239 "Regeneration of Cardiac Tissue Assisted by Bioactive Implants" (RECATABI).Arnal Pastor, MP.; Martínez Ramos, C.; Perez Garnes, M.; Monleón Pradas, M.; Vallés Lluch, A. (2013). Electrospun adherent-antiadherent bilayered membranes based on cross-linked hyaluronic acid for advanced tissue engineering applications. Materials Science and Engineering: C. 33(7):4086-4093. https://doi.org/10.1016/j.msec.2013.05.058S4086409333

    PLA/PCL electrospun membranes of tailored fibres diameter as drug delivery systems

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    [EN] The main electrospinning parameters, i.e., polymer concentration in the injectable solution, solvents used and their proportion, flow rate, voltage and distance to collector were herein systematically modified to analyse their particular influence in fibres diameter of electrospun membranes of poly(lactic acid), polycaprolactone and their mixture. As a result of this analysis, the procedures to obtain membranes of these polymers and blend with under- and above-micron-sized fibres were established, in which the solvents ratio (chloroform/methanol and dichloromethane/dimethylformamide) and voltage were found to play the major role. Moreover, the plausible differential effect of these fibres diameters (0.8 and 1.8 ¿m) in the controlled release of a molecule of interest was explored, using bovine serum albumin (BSA), proving that the most effective configuration for BSA release among those studied was the PLA-PCL combination in membranes of above-micron fibres diameter.The authors acknowledge Spanish Ministerio de Economia y Competitividad through DPI2015-65401-C3-2-R project, and the assistance and advice of the Electron Microscopy Service of the Universitat Politecnica de Valencia (Spain).Herrero-Herrero, M.; Gómez-Tejedor, J.; Vallés Lluch, A. (2018). PLA/PCL electrospun membranes of tailored fibres diameter as drug delivery systems. European Polymer Journal. 99:445-455. https://doi.org/10.1016/j.eurpolymj.2017.12.045S4454559
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