{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:39:37Z","timestamp":1790887177711,"version":"4.1.0"},"reference-count":40,"publisher":"SAGE Publications","issue":"3-4","license":[{"start":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T00:00:00Z","timestamp":1548979200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Tissue Engineering Part A"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:p>\n                    Current delivery of chemotherapy drugs to osteosarcoma is limited by the difficulties in overcoming the solid tumor microenvironment and the cardiotoxicity of doxorubicin (DOX). In previous work we found that phase separation could generate microspheres with high porosity. In this study, we applied these phase-separated porous microspheres as carriers for long-term anticancer drug delivery. Novel poly(propylene fumarate)-\n                    <jats:italic toggle=\"yes\">co<\/jats:italic>\n                    -poly(\n                    <jats:sc>l<\/jats:sc>\n                    -lactic acid) microspheres incorporating DOX were fabricated by thermally induced phase separation. Following embedding into oligo(poly[ethylene glycol] fumarate) hydrogel, the composite system showed prolonged and pH-responsive release of DOX.\n                    <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                    cytotoxicity study using osteosarcoma 143B cells showed substantial long-term cytotoxic effects for up to 30 days. As a result, the DOX drug delivery hydrogel developed in this work may have significant potential as a long-term and localized chemotherapy device that would be sensitive to the acidic microenvironment of osteosarcoma and other cancers.\n                  <\/jats:p>\n                  <jats:sec>\n                    <jats:title>Impact Statement<\/jats:title>\n                    <jats:p>A composite hydrogel embedded with porous microspheres fabricated by phase separation methods was developed and showed excellent long-term anticancer drug delivery capability to cancer cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/ten.tea.2018.0071","type":"journal-article","created":{"date-parts":[[2018,8,30]],"date-time":"2018-08-30T01:40:32Z","timestamp":1535593232000},"page":"172-182","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["Composite Hydrogel Embedded with Porous Microspheres for Long-Term pH-Sensitive Drug Delivery"],"prefix":"10.1177","volume":"25","author":[{"given":"Xifeng","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Physiology and Biomedical Engineering and Mayo Clinic College of Medicine, Rochester, Minnesota."},{"name":"Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin A.","family":"Fundora","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering and Mayo Clinic College of Medicine, Rochester, Minnesota."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zifei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering and Mayo Clinic College of Medicine, Rochester, Minnesota."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"Alan Lee","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lichun","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering and Mayo Clinic College of Medicine, Rochester, Minnesota."},{"name":"Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,2,13]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djm135"},{"key":"e_1_3_3_3_2","first-page":"2333","article-title":"Bone microenvironment has an influence on the histological response of osteosarcoma to chemotherapy: retrospective analysis and preclinical modeling","volume":"7","author":"Crenn V.","year":"2017","unstructured":"Crenn V., , Biteau K., , Amiaud J., et al. Bone microenvironment has an influence on the histological response of osteosarcoma to chemotherapy: retrospective analysis and preclinical modeling. Am J Cancer Res, 7, 2333, 2017.","journal-title":"Am J Cancer Res"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-9-399"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-0284-9_12"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.2165\/00148581-200810050-00005"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2015.1038237"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.5772\/67068"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2013.11.006"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1159\/000265166"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.2012.01567.x"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6602626"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD005006.pub3"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1039\/C7TB02570J"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.2174\/1573413711666150624170518"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2012.03.020"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.neo.7900096"},{"key":"e_1_3_3_18_2","first-page":"611","article-title":"Doxorubicin cardiotoxicity in children: reduced incidence of cardiac dysfunction associated with continuous-infusion schedules","volume":"8","author":"Berrak S.G.","year":"2001","unstructured":"Berrak S.G., , Ewer M.S., , Jaffe N., et al. Doxorubicin cardiotoxicity in children: reduced incidence of cardiac dysfunction associated with continuous-infusion schedules. Oncol Rep, 8, 611, 2001.","journal-title":"Oncol Rep"},{"key":"e_1_3_3_19_2","first-page":"631","article-title":"Combined pre-operative chemotherapy with intra-arterial cisplatin and continuous intravenous adriamycin for high grade osteosarcoma","volume":"6","author":"Rha S.Y.","year":"1999","unstructured":"Rha S.Y., , Chung H.C., , Gong S.J., et al. Combined pre-operative chemotherapy with intra-arterial cisplatin and continuous intravenous adriamycin for high grade osteosarcoma. Oncol Rep, 6, 631, 1999.","journal-title":"Oncol Rep"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2001.19.9.2413"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1893"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2009.09.001"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2009.03.022"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2009.09.069"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.06.045"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2004.07.004"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1021\/bm060096a"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1163\/156856201316883476"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/290602"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.1259"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0142-9612(03)00168-6"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1039\/C5RA19406G"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1039\/C5RA00508F"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2009.03.015"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10856-008-3545-8"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1088\/1748-6041\/2\/4\/001"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/bm200464x"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12806"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1590\/S1516-14392007000400023"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/bit.22912"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsmacrolett.6b00736"}],"container-title":["Tissue Engineering Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/ten.tea.2018.0071","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/ten.tea.2018.0071","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/ten.tea.2018.0071","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T04:49:17Z","timestamp":1777697357000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.1089\/ten.tea.2018.0071"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2]]},"references-count":40,"journal-issue":{"issue":"3-4","published-print":{"date-parts":[[2019,2]]}},"alternative-id":["10.1089\/ten.tea.2018.0071"],"URL":"https:\/\/doi.org\/10.1089\/ten.tea.2018.0071","relation":{},"ISSN":["1937-3341","1937-335X"],"issn-type":[{"value":"1937-3341","type":"print"},{"value":"1937-335X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2]]}}}