{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T16:33:09Z","timestamp":1787157189409,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30 AG021334"],"award-info":[{"award-number":["P30 AG021334"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["T32AG058527"],"award-info":[{"award-number":["T32AG058527"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["S10OD023548"],"award-info":[{"award-number":["S10OD023548"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1S10OD02522601"],"award-info":[{"award-number":["1S10OD02522601"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG046441"],"award-info":[{"award-number":["R01AG046441"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Wound Repair Regeneration"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic wounds are a common and debilitating condition associated with aging populations that impact more than 6.5 million patients in the United States. We have previously demonstrated the efficacy of daily topical 1% valsartan in treating wounds in diabetic mouse and pig models. Despite these promising results, there remains a need to develop an extended\u2010release formulation that would reduce patient burden by decreasing the frequency of daily applications. Here, we used nanotechnology to self\u2010assemble valsartan amphiphiles into a filamentous structure (val\u2010filaments) that would serve as a scaffold in wound beds and allow for steady, localised and tunable release of valsartan amphiphiles over 24\u2009days. Two topical treatments of this peptide\u2010based hydrogel on full\u2010thickness wounds in Zucker Diabetic Fatty rats resulted in faster rates of wound closure. By day 23, all val\u2010filament treated wounds were completely closed, as compared to one wound closed in the placebo group. Mechanistically, we observed enrichment of proteins involved in cell adhesion and energetics pathways, downregulation of Tgf\u2010\u03b2 signalling pathway mediators (pSmad2, pSmad3 and Smad4) and increased mitochondrial metabolic pathway intermediates. This study demonstrates the successful synthesis of a sustained\u2010release valsartan filament hydrogel, its impact on mitochondrial energetics and efficacy in treating diabetic wounds.<\/jats:p>","DOI":"10.1111\/wrr.12974","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T08:54:40Z","timestamp":1634806480000},"page":"927-937","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Valsartan\n                    <scp>nano\u2010filaments<\/scp>\n                    alter mitochondrial energetics and promote faster healing in diabetic rat wounds"],"prefix":"10.1111","volume":"29","author":[{"given":"Lolita S.","family":"Nidadavolu","sequence":"first","affiliation":[{"name":"Division of Geriatrics and Gerontology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Stern","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; Biomolecular Engineering Johns Hopkins University  Baltimore Maryland USA"},{"name":"Institute for NanoBioTechnology Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; Biomolecular Engineering Johns Hopkins University  Baltimore Maryland USA"},{"name":"Institute for NanoBioTechnology Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; Biomolecular Engineering Johns Hopkins University  Baltimore Maryland USA"},{"name":"Institute for NanoBioTechnology Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; Biomolecular Engineering Johns Hopkins University  Baltimore Maryland USA"},{"name":"Institute for NanoBioTechnology Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqiong","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Geriatrics and Gerontology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sela","family":"Marin","sequence":"additional","affiliation":[{"name":"Division of Geriatrics and Gerontology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjorie J.","family":"Antonio","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayane","family":"Yenokyan","sequence":"additional","affiliation":[{"name":"Johns Hopkins Biostatistics Center Johns Hopkins Bloomberg School of Public Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Boronina","sequence":"additional","affiliation":[{"name":"Mass Spectrometry and Proteomics Facility Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Cole","sequence":"additional","affiliation":[{"name":"Mass Spectrometry and Proteomics Facility Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Brian","family":"Foster","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3758-2425","authenticated-orcid":false,"given":"Conover","family":"Talbot","sequence":"additional","affiliation":[{"name":"Institute for Basic Biomedical Sciences Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaroslaw","family":"Jedrych","sequence":"additional","affiliation":[{"name":"Department of Dermatology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Smith","sequence":"additional","affiliation":[{"name":"Cell Biology Imaging Facility Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Rini","sequence":"additional","affiliation":[{"name":"Department of Art as Applied to Medicine, Division of Cellular and Molecular Medicine Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honggang","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; Biomolecular Engineering Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy D.","family":"Walston","sequence":"additional","affiliation":[{"name":"Division of Geriatrics and Gerontology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8186-0066","authenticated-orcid":false,"given":"Peter M.","family":"Abadir","sequence":"additional","affiliation":[{"name":"Division of Geriatrics and Gerontology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.avsg.2015.11.025"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.13332"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-47771-8_27"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9610(98)00183-4"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-010-9428-z"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2014.00439"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2017.09.030"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201900104"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz8985"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.9b01689"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/wrr.12272"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.6b00149"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euprot.2015.02.002"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.8b00702"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi0813s47"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100868"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1611406113"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glaa156"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-475X.2011.00703.x"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2013.0485"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a021873"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2012.0406"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002227"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2015.00170"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1101507108"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/wrr.12299"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1088\/1748-6041\/11\/4\/041001"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0229545"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-10882-1"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.30.1395"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.05.070"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1067-1927.2004.12601.x"},{"key":"e_1_2_9_35_1","volume-title":"Graph Clustering by Flow Simulation","author":"Van Dongern SM","year":"2009"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-7-488"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-436"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.03.036"}],"container-title":["Wound Repair and Regeneration"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/wrr.12974","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/wrr.12974","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/wrr.12974","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T16:11:37Z","timestamp":1787155897000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/wrr.12974"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,20]]},"references-count":37,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["10.1111\/wrr.12974"],"URL":"https:\/\/doi.org\/10.1111\/wrr.12974","archive":["Portico"],"relation":{},"ISSN":["1067-1927","1524-475X"],"issn-type":[{"value":"1067-1927","type":"print"},{"value":"1524-475X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,20]]},"assertion":[{"value":"2021-01-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}