An ibuprofen-eluting electrospun membrane prevents ureteral fibrosis by dampening macrophage-associated fibroblast activation
9 affiliations
- 1Department 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
- 2Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer Research, Nanjing, 210029, China
- 3Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, 201620, China
- 4Department of Urology, The Second People's Hospital of Wuhu, Wuhu, Anhui, 241100, China
- 5Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China
- 6Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
- 7Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, 201620, China; Corresponding author.
- 8Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China; Corresponding author.
- 9Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer Research, Nanjing, 210029, China; Corresponding author.
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.
Related
- Lactate-associated fibroblast–macrophage signaling in idiopathic pulmonary fibrosis: evidence boundaries and immunopharmacological opportunities
- An FCN1+ macrophage-associated SEMA3C–NRP1 axis is linked to fibroblast reprogramming in RA-ILD
- Diffuse gastrointestinal hemorrhage associated with emapalumab treatment of macrophage activation syndrome: A case report
- Macrophage Activation Syndrome Associated with Adult-onset Still's Disease Successfully Treated with Plasma Exchange and Canakinumab
- Monocyte-macrophage sensing of calciprotein particles in CKD-associated vascular calcification: lysosomal stress and inflammasome activation
BibTeX
@article{zhang2026ibuprofeneluting,
title = {{An ibuprofen-eluting electrospun membrane prevents ureteral fibrosis by dampening macrophage-associated fibroblast activation}},
author = {Xi Zhang and Da Zhong and Zihao Xu and Yi Li and Jie Zheng and Yuan Tian and Chao Qin and Renjun Pei and Jinglei Wu and Yichun Wang and Ninghong Song},
journal = {Materials Today Bio},
year = {2026},
month = oct,
doi = {10.1016/j.mtbio.2026.103771},
url = {https://doi.org/10.1016/j.mtbio.2026.103771},
note = {CC BY},
}
RIS
TY - JOUR
TI - An ibuprofen-eluting electrospun membrane prevents ureteral fibrosis by dampening macrophage-associated fibroblast activation
AU - Xi Zhang
AU - Da Zhong
AU - Zihao Xu
AU - Yi Li
AU - Jie Zheng
AU - Yuan Tian
AU - Chao Qin
AU - Renjun Pei
AU - Jinglei Wu
AU - Yichun Wang
AU - Ninghong Song
PY - 2026
DA - 2026/10/31
JO - Materials Today Bio
DO - 10.1016/j.mtbio.2026.103771
UR - https://doi.org/10.1016/j.mtbio.2026.103771
AB - 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.
SN - 2590-0064
ER -