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Incremental hypoxia inside the growing tumor mass drives epigenetic drug resistance by activating nongenetic repair of antiapoptotic DNA, which could be impaired by drug treatment. Hence, rescuing intertumor hypoxia by oxygen\u2010generating microparticles may promote susceptibility to antitumor drugs. Moreover, a tumor\u2010on\u2010a\u2010chip model enables user\u2010specified alternation of clinic\u2010derived samples. This study utilizes patient\u2010derived glioblastoma tissue to generate cell spheroids with size variations in a 3D microchannel network chip (GBM chip). As the spheroid size increases, epigenetic drug resistance is promoted with inward hypoxia severance, as supported by the spheroid size\u2010proportional expression of hypoxia\u2010inducible factor\u20101a in the chip. Loading antihypoxia microparticles onto the spheroid surface significantly reduces drug resistance by silencing the expression of critical epigenetic factor, resulting in significantly decreased cell invasiveness. The results are confirmed in vitro using cell line and patient samples in the chip as well as chip implantation into a hypoxic hindlimb ischemia model in mice, which is an unprecedented approach in the field.<\/jats:p>","DOI":"10.1002\/adhm.202102226","type":"journal-article","created":{"date-parts":[[2021,12,28]],"date-time":"2021-12-28T18:39:57Z","timestamp":1640716797000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Quenching Epigenetic Drug Resistance Using Antihypoxic Microparticles in Glioblastoma Patient\u2010Derived Chips"],"prefix":"10.1002","volume":"11","author":[{"given":"Sewoom","family":"Baek","sequence":"first","affiliation":[{"name":"Department of Brain Korea 21 FOUR Project for Medical Science Medical Device Engineering and Management Department of Medical Engineering Yonsei University College of Medicine  50\u20101 Yonsei\u2010ro, Seodaemun\u2010gu Seoul 03722 Republic of 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