{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:10:39Z","timestamp":1788952239921,"version":"build-2803163510"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100023652","name":"Sveu\u010dili\u0161te u Rijeci","doi-asserted-by":"publisher","award":["18-213; 6145"],"award-info":[{"award-number":["18-213; 6145"]}],"id":[{"id":"10.13039\/501100023652","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>\n                    Surgically induced acute kidney injury (AKI) may involve both ischemia\u2013reperfusion and direct mechanical damage to the renal parenchyma, potentially affecting subsequent tissue repair and remodeling. Although bone morphogenetic protein-7 (BMP-7) has shown renoprotective effects in experimental models of acute kidney injury, most studies have evaluated systemic administration in relatively homogeneous injury models. The effects of local BMP-7 delivery in the setting of combined ischemic and surgical parenchymal injury remain insufficiently defined. In this study, a rat model combining transient renal ischemia\u2013reperfusion with a standardized parenchymal incision was used to investigate renal repair following surgical injury. Recombinant human BMP-7 (rhBMP-7) was applied locally to the injured renal parenchyma using Surgicel as a carrier. Serum renal function measures, tubular injury, proliferative activity, fibrosis-associated remodeling, and selected repair- and BMP-associated signaling markers were evaluated at 7 and 28 days after injury. Local Surgicel\/rhBMP-7 application was associated with lower serum blood urea nitrogen and creatinine levels at day 7 compared with the suturing-only surgical-injury group. Histopathological tubular injury was observed in both groups, without significant between-group differences. Increased numbers of proliferating cell nuclear antigen (PCNA)-positive tubular epithelial cells were observed in the Surgicel\/rhBMP-7 group at both analyzed time points. Compared with the suturing-only group, the Surgicel\/rhBMP-7 group showed higher Wnt-4 immunoreactivity at both time points and higher phosphorylated Smad1\/5\/8 immunoreactivity at day 28, compatible with differences in BMP-associated signaling. Histological analysis demonstrated a reduced collagen-positive area in the Surgicel\/rhBMP-7 group, accompanied by a time-dependent pattern of\n                    <jats:italic>\u03b1<\/jats:italic>\n                    -SMA expression. In conclusion, local Surgicel\/rhBMP-7 delivery was associated with differences in functional, tubular proliferative, repair-associated signaling, and histological remodeling responses following combined renal ischemia\u2013reperfusion and surgical parenchymal injury. These findings support further evaluation of this localized delivery approach in more comprehensively controlled models of surgical kidney injury.\n                  <\/jats:p>","DOI":"10.3389\/fmed.2026.1941191","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:16:54Z","timestamp":1788949014000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Local Surgicel\/rhBMP-7 delivery is associated with renal repair responses after surgically induced acute kidney injury"],"prefix":"10.3389","volume":"13","author":[{"given":"Ante","family":"Jak\u0161i\u0107","sequence":"first","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, University of Rijeka","place":["Rijeka, Croatia"]},{"name":"Department of Urology, Clinical Hospital Center Rijeka","place":["Rijeka, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragica","family":"Bobinac","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, University of Rijeka","place":["Rijeka, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vedran","family":"Micek","sequence":"additional","affiliation":[{"name":"Institute for Medical Research and Occupational Health","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"\u0106eli\u0107 \u010crnac","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, University of Rijeka","place":["Rijeka, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirna","family":"Bobinac","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Reanimatology, Emergency and Intensive Care Medicine, Faculty of Medicine, University of Rijeka","place":["Rijeka, Croatia"]},{"name":"Clinic for Anesthesia, Intensive Care Medicine and Pain Management, Clinical Hospital Center Rijeka","place":["Rijeka, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marin","family":"O\u0161tri\u0107","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine, University of Rijeka","place":["Rijeka, Croatia"]},{"name":"Department of Cardiothoracic Surgery, Clinical Hospital Center Rijeka","place":["Rijeka, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josip","family":"\u0160panjol","sequence":"additional","affiliation":[{"name":"Department of Urology, Clinical Hospital Center Rijeka","place":["Rijeka, Croatia"]},{"name":"Department of Urology, Faculty of Medicine, University of Rijeka","place":["Rijeka, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Pilipovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Basic and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Rijeka","place":["Rijeka, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1146\/annurev-med-050214-013407","article-title":"Acute kidney injury","volume":"67","author":"Zuk","year":"2016","journal-title":"Annu Rev Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"699192","DOI":"10.3389\/fimmu.2021.699192","article-title":"Comprehensive molecular and cellular characterization of acute kidney injury progression to renal fibrosis","volume":"12","author":"Wu","year":"2021","journal-title":"Front Immunol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"114","DOI":"10.3389\/fphys.2015.00114","article-title":"Role of bone morphogenetic protein-7 in renal fibrosis","volume":"6","author":"Li","year":"2015","journal-title":"Front Physiol"},{"key":"B4","doi-asserted-by":"crossref","first-page":"3095","DOI":"10.1016\/j.bbadis.2017.09.011","article-title":"BMP7-induced-Pten inhibits Akt and prevents renal fibrosis","volume":"1863","author":"Higgins","year":"2017","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"B5","doi-asserted-by":"publisher","first-page":"117860","DOI":"10.1016\/j.lfs.2020.117860","article-title":"Renal ischemia\/reperfusion injury: an insight on in vitro and in vivo models","volume":"256","author":"Shiva","year":"2020","journal-title":"Life Sci"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2097","DOI":"10.1681\/ASN.2019020204","article-title":"Gentamicin-induced acute kidney injury in an animal model involves programmed necrosis of the collecting duct","volume":"31","author":"Huang","year":"2020","journal-title":"J. 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