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Poly(vinyl alcohol co-vinyl acetate) as a novel scaffold for mammalian cell culture and controlled drug release

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Abstract

Tissue engineering requires novel smart materials to sustain cell growth, tissue regeneration and in situ drug release in a controlled mode. Also, biocompatible synthesis methods are needed to immobilize biologically active compounds. Poly(vinyl alcohol co-vinyl acetate) (PAcVA) was synthesized at 37 °C using glutaraldehyde (GA) as a crosslinking agent. The mechanical characteristics of the polymer were manipulated by varying crosslinking degrees using different GA concentrations. Materials with Young’s modules similar to soft tissues, adequate for tissue engineering, were obtained. PAcVA was a pH-responsive material with maximum swelling at pH 5.8. When hydrated, PAcVA was electro-responsive. Fluorescein was used as a model molecule to characterize the releasing properties of the polymer. Effective diffusivities were a function of the crosslinking degree. Release rates were proportional to temperature and were faster at lower GA contents. According to a fit to the Korsmeyer–Peppas’ model, diffusion at 5 and 10% GA was Fickian, but at 20% GA, diffusion was abnormal. To promote cell attachment and neutralize free aldehyde groups, PAcVA hydrogels were covered with poly-l-lysine and laminin, which supported growth of lung carcinoma and mouse hypothalamic cells without signs of cytotoxicity or oxidative stress. An intelligent low-cost hydrogel with properties that can be easily modulated was synthesized and fully characterized. Its properties make it suitable for tissue engineering applications, as they mimic the mechanical properties of natural tissues.

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Acknowledgements

Research performed thanks to the financial support of the Programa UNAM-DGAPA-PAPIIT IT-200416. F. Villanueva received a scholarship from CONACyT during her graduate studies. We thank Mariana Ramírez Gilly (Facultad de Química UNAM), Melina Tapia Tapia (Instituto de Química UNAM), Manuel Aguilar Franco (Laboratorio Central de Microscopía UNAM), Martha A. Contreras, Ruth Pastor, Vanessa Hernández, Guadalupe Zavala Padilla, Arturo Pimentel Cabrera and the National Laboratory of Advanced Microscopy (LNMA-IBT-UNAM) for technical support.

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Authors and Affiliations

  1. Instituto de Biotecnología, Universidad Nacional Autónoma de México, Ave. Universidad 2001. Col. Chamilpa, 62210, Cuernavaca, Morelos, Mexico

    Francisca Villanueva-Flores, Alberto Porras-Sanjuanico, Leonor Pérez-Martínez, Octavio T. Ramírez & Laura A. Palomares

  2. Instituto de Energías Renovables, Universidad Nacional Autónoma de México, Priv. Xochicalco S/N, 62580, Temixco, Morelos, Mexico

    Margarita Miranda-Hernández & Hailin Hu

  3. Instituto de Ciencias Aplicadas y Tecnología, Universidad Nacional Autónoma de México, Circuito Exterior S/N. Ciudad Universitaria, 04510, Ciudad de México, Mexico

    José O. Flores-Flores

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  1. Francisca Villanueva-Flores
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10853_2019_3402_MOESM1_ESM.docx

Supplementary information (S): File S1. Detailed procedure to obtain Eq. 6, used to determine effective diffusivities of fluorescein across PAcVA films (DOCX 18 kb)

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Villanueva-Flores, F., Miranda-Hernández, M., Flores-Flores, J.O. et al. Poly(vinyl alcohol co-vinyl acetate) as a novel scaffold for mammalian cell culture and controlled drug release. J Mater Sci 54, 7867–7882 (2019). https://doi.org/10.1007/s10853-019-03402-1

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