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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,10,3]]},"abstract":"<jats:p>\n                    The immune isolation of cells within devices has the potential to enable long-term protein replacement and functional cures for a range of diseases, without requiring immune suppressive therapy. However, a lack of vasculature and the formation of fibrotic capsules around cell immune-isolating devices limits oxygen availability, leading to hypoxia and cell death in vivo. This is particularly problematic for pancreatic islet cells that have high O\n                    <jats:sub>2<\/jats:sub>\n                    requirements. Here, we combine bioelectronics with encapsulated cell therapies to develop the first wireless, battery-free oxygen-generating immune-isolating device (O\n                    <jats:sub>2<\/jats:sub>\n                    -Macrodevice) for the oxygenation and immune isolation of cells in vivo. The system relies on electrochemical water splitting based on a water-vapor reactant feed, sustained by wireless power harvesting based on a flexible resonant inductive coupling circuit. As such, the device does not require pumping, refilling, or ports for recharging and does not generate potentially toxic side products. Through systematic in vitro studies with primary cell lines and cell lines engineered to secrete protein, we demonstrate device performance in preventing hypoxia in ambient oxygen concentrations as low as 0.5%. Importantly, this device has shown the potential to enable subcutaneous (SC) survival of encapsulated islet cells, in vivo in awake, freely moving, immune-competent animals. Islet transplantation in Type I Diabetes represents an important application space, and 1-mo studies in immune-competent animals with SC implants show that the O\n                    <jats:sub>2<\/jats:sub>\n                    -Macrodevice allows for survival and function of islets at high densities (~1,000 islets\/cm\n                    <jats:sup>2<\/jats:sup>\n                    ) in vivo without immune suppression and induces normoglycemia in diabetic animals.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2311707120","type":"journal-article","created":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T13:36:23Z","timestamp":1695389783000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":39,"title":["A wireless, battery-free device enables oxygen generation and immune protection of therapeutic xenotransplants in vivo"],"prefix":"10.1073","volume":"120","author":[{"given":"Siddharth R.","family":"Krishnan","sequence":"first","affiliation":[{"name":"David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139"},{"name":"Department of Anesthesiology, Boston Children\u2019s Hospital, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Liu","sequence":"additional","affiliation":[{"name":"David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139"},{"name":"Department of Anesthesiology, Boston Children\u2019s Hospital, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Bochenek","sequence":"additional","affiliation":[{"name":"David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139"},{"name":"Department of Anesthesiology, Boston Children\u2019s Hospital, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suman","family":"Bose","sequence":"additional","affiliation":[{"name":"David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139"},{"name":"Department of Anesthesiology, Boston Children\u2019s Hospital, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nima","family":"Khatib","sequence":"additional","affiliation":[{"name":"David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139"},{"name":"Department of Anesthesiology, Boston Children\u2019s Hospital, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Walters","sequence":"additional","affiliation":[{"name":"David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139"},{"name":"Department of Anesthesiology, Boston Children\u2019s Hospital, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"O\u2019Keeffe","sequence":"additional","affiliation":[{"name":"David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139"},{"name":"Department of Anesthesiology, Boston Children\u2019s Hospital, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Facklam","sequence":"additional","affiliation":[{"name":"David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139"},{"name":"Department of Bioengineering, Massachusetts Institute of Technology, Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4255-0492","authenticated-orcid":false,"given":"Robert","family":"Langer","sequence":"additional","affiliation":[{"name":"David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139"},{"name":"Department of Anesthesiology, Boston Children\u2019s Hospital, Boston, MA 02115"},{"name":"Department of Bioengineering, Massachusetts Institute of Technology, Cambridge, MA 02139"},{"name":"Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139"},{"name":"Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel G.","family":"Anderson","sequence":"additional","affiliation":[{"name":"David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139"},{"name":"Department of Anesthesiology, Boston Children\u2019s Hospital, Boston, MA 02115"},{"name":"Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139"},{"name":"Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139"},{"name":"Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,9,22]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6776628"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-018-0275-1"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-020-0538-5"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.14642"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4030"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2007.10.056"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2007.02.010"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0376-7388(99)00062-9"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1014639332543"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(02)00227-2"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5b00679"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2009.02.002"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1708806115"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0402-339"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2016.232"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-013-2921-1"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.2006.0183"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.3727\/096368912X657341"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2018.10.012"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1089\/10430349950017969"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.01-0590fje"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25343"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1602\/neurorx.1.4.382"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/35072572"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2014.02.007"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199606150-00001"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00461694"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00869269"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3211"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1113560109"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26126-w"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","unstructured":"K. Yang A therapeutic convection\u2013enhanced macroencapsulation device for enhancing \u03b2 cell viability and insulin secretion. Proc. Natl. Acad. Sci. U.S.A. 118 e2101258118 (2021). e2101258118","DOI":"10.1073\/pnas.2101258118"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-0269-7"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1267916"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1708420114"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1317561110"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb08497.x"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/aenm.201800338"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1039\/c3ee42143k"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1039\/c1ee01203g"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpowsour.2007.03.061"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1149\/1.1836669"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1968.tb20277.x"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.6b00159"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41928-018-0175-0"},{"key":"e_1_3_4_46_2","doi-asserted-by":"crossref","unstructured":"G. Shin Flexible near-field wireless optoelectronics as subdermal implants for broad applications in optogenetics. Neuron 93 509\u2013521.e3 (2017).","DOI":"10.1016\/j.neuron.2016.12.031"},{"key":"e_1_3_4_47_2","doi-asserted-by":"crossref","unstructured":"S. Han Battery-free wireless sensors for full-body pressure and temperature mapping. Sci. Trans. Med. 10 eaan4950 (2018). eaan4950","DOI":"10.1126\/scitranslmed.aan4950"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0183780"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ces.2009.06.028"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-23862-w"},{"key":"e_1_3_4_51_2","doi-asserted-by":"crossref","unstructured":"C. Colton E. Avgoustiniatos Bioengineering in development of the hybrid artificial pancreas. J. Biomech. Eng. 113 152\u2013170 (1991).","DOI":"10.1115\/1.2891229"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1097\/MPA.0000000000001050"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1097\/MPA.0b013e31815ccad2"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-2727"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1039\/b508097e"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1577"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2016.01.029"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0764-4469(01)01350-6"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2011.05.006"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1203535"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau7187"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.2006.0417"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1002\/term.540"},{"key":"e_1_3_4_64_2","doi-asserted-by":"crossref","unstructured":"H. Luan Complex 3D microfluidic architectures formed by mechanically guided compressive buckling. Sci. Adv. 7 eabj3686 (2021). eabj3686","DOI":"10.1126\/sciadv.abj3686"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abl8532"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.123"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2017.12.007"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00592-014-0627-6"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2311707120","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T13:36:45Z","timestamp":1695389805000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2311707120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,22]]},"references-count":68,"journal-issue":{"issue":"40","published-print":{"date-parts":[[2023,10,3]]}},"alternative-id":["10.1073\/pnas.2311707120"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2311707120","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,22]]},"assertion":[{"value":"2023-07-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2311707120"}}