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      A 3D‐Engineered Conformal Implant Releases DNA Nanocomplexs for Eradicating the Postsurgery Residual Glioblastoma

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          Abstract

          Gene therapy has great promise for glioblastoma treatment; however, it remains a great challenge to efficiently deliver genes to the brain. The incomplete resection of glioblastoma always leads to poor prognosis. Here, a 3D‐engineered conformal implant for eradicating the postsurgery residual glioblastoma is designed. This implant is constructed by 3D‐printing technology to match the tumor cavity and release an oncolytic virus‐inspired DNA nanocomplex to kill glioblastoma cells through apoptosis induction. Meanwhile, a 3D‐engineered subcutaneous glioblastoma xenograft is built to mimic the resection tumor cavity in mice. Insertion of the implant into the glioblastoma resection cavity efficiently delays tumor recurrence and significantly prolongs overall survival. This study provides a proof‐of‐concept of glioblastoma therapy using a conformal implant that releases oncolytic DNA nanocomplexs. This strategy can lead to the development of future precision therapy for eradicating postsurgery residual tumors.

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          Most cited references14

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          Gelatin-Methacryloyl Hydrogels: Towards Biofabrication-Based Tissue Repair.

          Research over the past decade on the cell-biomaterial interface has shifted to the third dimension. Besides mimicking the native extracellular environment by 3D cell culture, hydrogels offer the possibility to generate well-defined 3D biofabricated tissue analogs. In this context, gelatin-methacryloyl (gelMA) hydrogels have recently gained increased attention. This interest is sparked by the combination of the inherent bioactivity of gelatin and the physicochemical tailorability of photo-crosslinkable hydrogels. GelMA is a versatile matrix that can be used to engineer tissue analogs ranging from vasculature to cartilage and bone. Convergence of biological and biofabrication approaches is necessary to progress from merely proving cell functionality or construct shape fidelity towards regenerating tissues. GelMA has a critical pioneering role in this process and could be used to accelerate the development of clinically relevant applications.
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            Hyaluronic acid-decorated dual responsive nanoparticles of Pluronic F127, PLGA, and chitosan for targeted co-delivery of doxorubicin and irinotecan to eliminate cancer stem-like cells.

            Dual responsive nanoparticles are developed for co-delivery of multiple anticancer drugs to target the drug resistance mechanisms of cancer stem-like cells (CSCs). The nanoparticles consist of four polymers approved by the Food and Drug Administration (FDA) for medical use: Poly(d,l-lactide-co-glycolide) (PLGA), Pluronic F127 (PF127), chitosan, and hyaluronic acid (HA). By combining PLGA and PF127 together, more stable and uniform-sized nanoparticles can be obtained than using PLGA or PF127 alone. The HA is used for not only actively targeting CSCs to reduce their drug resistance due to dormancy (i.e., slow metabolism), but also replacing the commonly used poly(vinyl alcohol) as a stabilizing agent to synthesize the nanoparticles using the double-emulsion approach and to allow for acidic pH-triggered drug release and thermal responsiveness. Besides minimizing drug efflux from CSCs, the nanoparticles encapsulated with doxorubicin hydrochloride (DOX, hydrophilic) and irinotecan (CPT, hydrophobic) to inhibit the activity of topoisomerases II and I, respectively, can fight against the CSC drug resistance associated with their enhanced DNA repair and anti-apoptosis. Ultimately, the two drugs-laden nanoparticles can be used to efficiently destroy the CSCs both in vitro and in vivo with up to ∼500 times of enhancement compared to the simple mixture of the two drugs.
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              Biopsy versus partial versus gross total resection in older patients with high-grade glioma: a systematic review and meta-analysis.

              Optimal extent of surgical resection (EOR) of high-grade gliomas (HGGs) remains uncertain in the elderly given the unclear benefits and potentially higher rates of mortality and morbidity associated with more extensive degrees of resection.
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                Author and article information

                Contributors
                qingmao2000@163.com
                goumaling@scu.edu.cn
                Journal
                Adv Sci (Weinh)
                Adv Sci (Weinh)
                10.1002/(ISSN)2198-3844
                ADVS
                Advanced Science
                John Wiley and Sons Inc. (Hoboken )
                2198-3844
                30 March 2017
                August 2017
                : 4
                : 8 ( doiID: 10.1002/advs.v4.8 )
                : 1600491
                Affiliations
                [ 1 ] State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University and Collaborative Innovation Center of Biotherapy Chengdu P. R. China
                [ 2 ] Department of Neurosurgery West China Hospital Sichuan University Chengdu P. R. China
                [ 3 ] School of Materials Science and Engineering Sichuan University Chengdu Sichuan 610065 P. R. China
                [ 4 ] Department of Nanoengineering Institute of Engineering in Medicine 245B SME Building MC 0448 University of California San Diego 9500 Gilman Drive La Jolla CA 92093 USA
                [ 5 ] Department of Biomedical Engineering Tsinghua University School of Medicine Beijing P. R. China
                [ 6 ] State key laboratory for manufacturing systems engineering Xi'an Jiaotong University Xi'an 710049 China
                Author notes
                Article
                ADVS312
                10.1002/advs.201600491
                5566247
                28852611
                33097891-2108-443f-9c8d-793bafd3a633
                © 2017 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 04 December 2016
                : 01 February 2017
                Page count
                Figures: 5, Tables: 0, Pages: 8, Words: 5011
                Funding
                Funded by: National Natural Science Foundation
                Award ID: 81422025
                Award ID: 81572990
                Funded by: Sichuan Province Youth Science and Technology Fund
                Award ID: 2016JQ0020
                Award ID: 2015FZ0040
                Award ID: 2015SZ0049
                Funded by: Sichuan province science and technology support plan
                Award ID: 2015FZ0040
                Award ID: 2015SZ0049
                Award ID: 0040205301F10
                Funded by: Outstanding Youth Fund of Sichuan University
                Award ID: 2014SCU04A12
                Categories
                Full Paper
                Full Papers
                Custom metadata
                2.0
                advs312
                August 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.1.7 mode:remove_FC converted:22.08.2017

                3d printing,conformal implants,cancer gene therapy,nanoparticles

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