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      3D Printed porous polyamide macrocapsule combined with alginate microcapsules for safer cell-based therapies

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          Abstract

          Cell microencapsulation is an attractive strategy for cell-based therapies that allows the implantation of genetically engineered cells and the continuous delivery of de novo produced therapeutic products. However, the establishment of a way to retrieve the implanted encapsulated cells in case the treatment needs to be halted or when cells need to be renewed is still a big challenge. The combination of micro and macroencapsulation approaches could provide the requirements to achieve a proper immunoisolation, while maintaining the cells localized into the body. We present the development and characterization of a porous implantable macrocapsule device for the loading of microencapsulated cells. The device was fabricated in polyamide by selective laser sintering (SLS), with controlled porosity defined by the design and the sintering conditions. Two types of microencapsulated cells were tested in order to evaluate the suitability of this device; erythropoietin (EPO) producing C 2C 12 myoblasts and Vascular Endothelial Growth Factor (VEGF) producing BHK fibroblasts. Results showed that, even if the metabolic activity of these cells decreased over time, the levels of therapeutic protein that were produced and, importantly, released to the media were stable.

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          Biocompatibility and osteogenesis of biomimetic nano-hydroxyapatite/polyamide composite scaffolds for bone tissue engineering.

          In this study, we prepared nano-hydroxyapatite/polyamide (n-HA/PA) composite scaffolds utilizing thermally induced phase inversion processing technique. The macrostructure and morphology as well as mechanical strength of the scaffolds were characterized. Mesenchymal stem cells (MSCs) derived from bone marrow of neonatal rabbits were cultured, expanded and seeded on n-HA/PA scaffolds. The MSC/scaffold constructs were cultured for up to 7 days and the adhesion, proliferation and differentiation of MSCs into osteoblastic phenotype were determined using MTT assay, alkaline phosphatase (ALP) activity and collagen type I (COL I) immunohistochemical staining and scanning electronic microscopy (SEM). The results confirm that n-HA/PA scaffolds are biocompatible and have no negative effects on the MSCs in vitro. To investigate the in vivo biocompatibility and osteogenesis of the composite scaffolds, both pure n-HA/PA scaffolds and MSC/scaffold constructs were implanted in rabbit mandibles and studied histologically and microradiographically. The results show that n-HA/PA composite scaffolds exhibit good biocompatibility and extensive osteoconductivity with host bone. Moreover, the introduction of MSCs to the scaffolds dramatically enhanced the efficiency of new bone formation, especially at the initial stage after implantation. In long term (more than 12 weeks implantation), however, the pure scaffolds show as good biocompatibility and osteogenesis as the hybrid ones. All these results indicate that the scaffolds fulfill the basic requirements of bone tissue engineering scaffold, and have the potential to be applied in orthopedic, reconstructive and maxillofacial surgery.
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            Natural polymers for the microencapsulation of cells.

            The encapsulation of living mammalian cells within a semi-permeable hydrogel matrix is an attractive procedure for many biomedical and biotechnological applications, such as xenotransplantation, maintenance of stem cell phenotype and bioprinting of three-dimensional scaffolds for tissue engineering and regenerative medicine. In this review, we focus on naturally derived polymers that can form hydrogels under mild conditions and that are thus capable of entrapping cells within controlled volumes. Our emphasis will be on polysaccharides and proteins, including agarose, alginate, carrageenan, chitosan, gellan gum, hyaluronic acid, collagen, elastin, gelatin, fibrin and silk fibroin. We also discuss the technologies commonly employed to encapsulate cells in these hydrogels, with particular attention on microencapsulation.
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              Applications of synthetic polymers in clinical medicine

              M.F. Maitz (2015)
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                Author and article information

                Contributors
                mar.alvarez@imb-cnm.csic.es
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                31 May 2018
                31 May 2018
                2018
                : 8
                : 8512
                Affiliations
                [1 ]ISNI 0000000121671098, GRID grid.11480.3c, NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, , University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, ; 01006 Vitoria-Gasteiz, Spain
                [2 ]GRID grid.7080.f, Instituto de Microelectronica de Barcelona (IMB-CNM, CSIC), Campus UAB, 08193 Bellaterra, ; Barcelona, Spain
                [3 ]Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain
                Author information
                http://orcid.org/0000-0002-8666-622X
                http://orcid.org/0000-0003-4590-4401
                Article
                26869
                10.1038/s41598-018-26869-5
                5981392
                29855599
                1e2bee62-179f-4b3e-b65d-fb6aa6051f5c
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 25 January 2018
                : 17 May 2018
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