{
  "abstract": "Background: Ureteral stricture is driven by unresolved inflammation and progressive matrix deposition, yet mechanism-guided local therapies remain limited. Methods: We integrated spatial transcriptomics of human normal and stricture ureters with an in-house scRNA-seq reference generated from three stricture specimens and independently evaluated annotation using the normal ureter dataset GSE194129. Urothelial injury-conditioned medium (UICM), primary ureteral fibroblasts, and THP-1-derived macrophages were used to model epithelial-immune-stromal signaling. An ibuprofen-functionalized PCL/gelatin electrospun membrane (P/G-PLL-IBU) was characterized and tested in a rabbit ureteral thermal-injury model. Results: Spatial analysis identified a fibro-inflammatory niche with co-enrichment of fibroblast and macrophage programs in stenotic regions. Low normal-reference feature spots displayed cytoskeletal remodeling-associated signatures. UICM contained increased IL-6 and HMGB1 and elevated LDH release, induced an inflammatory fibroblast-like state, and produced a macrophage activation state dominated by pro-inflammatory features. Conditioned medium from UICM-activated macrophages enhanced FN1, COL1A1, α-SMA, and Smad2/3 phosphorylation in UICM-primed fibroblasts. Soluble ibuprofen suppressed macrophage NF-κB/COX-2-associated activation, and conditioned medium from treated cultures elicited lower profibrotic responses in fibroblasts. PGE 2 add-back partially restored these responses. P/G-PLL-IBU preserved nanofibrous architecture, released ibuprofen for 56 days, and showed favorable hemocompatibility and cytocompatibility. In rabbits, P/G-PLL-IBU reduced early and long-term collagen deposition and upper urinary tract dilation for up to 90 days. Delayed membrane placement produced no detectable reversal of established fibrosis within the 30-day post-treatment observation window. Conclusion: Together, human spatial mapping and stepwise in vitro analyses link macrophage activation to fibroblast Smad2/3-associated remodeling in ureteral stricture, and local ibuprofen delivery via an electrospun membrane can blunt this trajectory after ureteral injury.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China; Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer Research, Nanjing, 210029, China",
    "Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer Research, Nanjing, 210029, China",
    "Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, 201620, China",
    "Department of Urology, The Second People's Hospital of Wuhu, Wuhu, Anhui, 241100, China",
    "Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China",
    "Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China",
    "Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, 201620, China; Corresponding author.",
    "Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China; Corresponding author.",
    "Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer Research, Nanjing, 210029, China; Corresponding author."
  ],
  "article_type": null,
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  "author_total": 11,
  "authors": [
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        0
      ],
      "name": "Xi Zhang"
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    {
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        1
      ],
      "name": "Da Zhong"
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    {
      "affs": [
        0
      ],
      "name": "Zihao Xu"
    },
    {
      "affs": [
        2
      ],
      "name": "Yi Li"
    },
    {
      "affs": [
        3
      ],
      "name": "Jie Zheng"
    },
    {
      "affs": [
        4
      ],
      "name": "Yuan Tian"
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    {
      "affs": [
        5
      ],
      "name": "Chao Qin"
    },
    {
      "affs": [
        4
      ],
      "name": "Renjun Pei"
    },
    {
      "affs": [
        6
      ],
      "name": "Jinglei Wu"
    },
    {
      "affs": [
        7
      ],
      "name": "Yichun Wang"
    },
    {
      "affs": [
        8
      ],
      "name": "Ninghong Song"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/36jbdzcmers6g.bib",
  "cited_by": 0,
  "doi": "10.1016/j.mtbio.2026.103771",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2590006426010161",
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  "issns": [
    "2590-0064"
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  "landing_url": "https://doi.org/10.1016/j.mtbio.2026.103771",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "lcc",
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      "lcc",
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      "2729|Ureteral procedures and complications"
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  "openalex": "W7223272791",
  "pdf_url": null,
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  "pmid": null,
  "published": "2026-10-31",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/36jbdzcmers6g.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T14:22:44Z",
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  "title": "An ibuprofen-eluting electrospun membrane prevents ureteral fibrosis by dampening macrophage-associated fibroblast activation",
  "title_text": "An ibuprofen-eluting electrospun membrane prevents ureteral fibrosis by dampening macrophage-associated fibroblast activation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T14:20:43Z",
  "url": "https://research.draconitic.com/paper/36jbdzcmers6g",
  "venue": "Materials Today Bio",
  "versions": []
}