{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:46:49Z","timestamp":1790279209867,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["52025051"],"award-info":[{"award-number":["52025051"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFE0114900"],"award-info":[{"award-number":["2018YFE0114900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small Methods"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Red blood cells (RBCs) play a crucial role in delivering oxygen to tissues with their distinctive shape. However, the mechanisms underlying cellular deformation and rupture due to stress, which lead to diseases such as acute renal failure, pulmonary hypertension, anemia, and gallstone formation, remain poorly understood. Here, we investigate the mechanism of membrane protrusion and present a highly effective method to restore the morphology and function of damaged RBCs. We propose ultrasound\u2010triggered nanodroplets loaded with oxygen and glucose to increase the local concentrations of these substances around RBCs and facilitate the rapid release of their payloads to repair fatigued RBCs under ultrasound. We identify a critical membrane protrusion length threshold of one\u2010third the cell's diameter, beyond which the skeleton structure fractures and prevents repair. Our findings demonstrate how nanodroplets can efficiently deliver oxygen and glucose to expose membrane connection and trigger cytoskeleton reorganization to repair cellular structure. In an in vitro extracorporeal membrane oxygenation (ECMO) model, our method reduces the percentage of abnormal RBCs to 5% and decreases free hemoglobin concentration by 50%. This work offers new insights into RBC rejuvenation and strongly supports the potential of ultrasound\u2010triggered nanodroplets for revitalizing fatigued RBCs, contributing to long\u2010term health and well\u2010being.<\/jats:p>","DOI":"10.1002\/smtd.202502128","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T06:31:03Z","timestamp":1769063463000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Restoring the Morphology and Function of Damaged Red Blood Cells"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4845-6464","authenticated-orcid":false,"given":"Yunfan","family":"Pan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Tribology Department of Mechanical Engineering Tsinghua University  Beijing China"},{"name":"Renal Division and Division of Engineering in Medicine Department of Medicine Brigham and Women's Hospital Harvard Medical School, Harvard University Boston MA USA"},{"name":"Interdisciplinary Institute for Medical Engineering Fuzhou University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjian","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Tribology Department of Mechanical Engineering Tsinghua University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuilin","family":"Meng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Tribology Department of Mechanical Engineering Tsinghua University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Li","sequence":"additional","affiliation":[{"name":"School of Mechanical Engineering University of Science and Technology Beijing  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke P.","family":"Lee","sequence":"additional","affiliation":[{"name":"Renal Division and Division of Engineering in Medicine Department of Medicine Brigham and Women's Hospital Harvard Medical School, Harvard University Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1134-0989","authenticated-orcid":false,"given":"Haosheng","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Tribology Department of Mechanical Engineering Tsinghua University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1910336116"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909533107"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2018.10"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aay7243"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2004.01.002"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2210819119"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMclde1804601"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1600968113"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.50217"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1051\/ject\/200840257"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.23.2.219"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2013.11.022"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1039\/d0lc00411a"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41378\u2010019\u20100097\u20107"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00392\u2010021\u201001862\u20107"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1608438113"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010022\u201005499\u2010y"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201032912\u2010x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202003679"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adf3329"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201043067\u20108"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201701429"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202202281"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200200550"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:DDAS.0000042232.98927.91"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/rb\/rbad045"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551\u2010022\u201000870\u2010w"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/rb\/rbad045"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010018\u201005079\u20107"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2020.06.016"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1247\/csf.06017"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaw4466"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1039\/d1lc00598g"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3672117"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.9.4378"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01148"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200602085"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz3050"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1039\/c1ib00044f"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/aor.13769"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1097\/mat.0000000000000252"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aao1016"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/pcc.0000000000001699"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.9.4378"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.248385"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3672117"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/228726a0"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi201623v"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010025\u201018028\u20104"},{"key":"e_1_2_10_51_1","first-page":"99","volume-title":"Methods in Molecular Biology","author":"Svitkina T.","year":"2016"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2014.06.031"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpc.2016.09.018"}],"container-title":["Small Methods"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/smtd.202502128","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/smtd.202502128","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/smtd.202502128","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T20:27:59Z","timestamp":1773001679000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/smtd.202502128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,21]]},"references-count":52,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/smtd.202502128"],"URL":"https:\/\/doi.org\/10.1002\/smtd.202502128","archive":["Portico"],"relation":{},"ISSN":["2366-9608","2366-9608"],"issn-type":[{"value":"2366-9608","type":"print"},{"value":"2366-9608","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,21]]},"assertion":[{"value":"2025-10-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02128"}}