A topologically engineered hydrogel platform targeting IL11 promotes renal repair after partial nephrectomy
6 affiliations
- 1School of Medicine, Institute of Transplant Medicine, Department of Surgical Intensive Care Unit, Tianjin First Central Hospital, Nankai University, Tianjin, 300071, China
- 2State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, 300071, China
- 3Tingo Regenerative Medicine Technology Co. LTD, Tianjin, 300301, China
- 4Shandong Qilu Stem Cell Engineering Co. LTD, Jinan, 250101, China
- 5Department of Surgical Intensive Care Unit, Tianjin First Central Hospital, Nankai University, Tianjin, 300071, China
- 6Department of Nephrology, Tianjin First Central Hospital, Nankai University, Tianjin, 300071, China
Abstract
Partial nephrectomy (PN) is the gold standard for treating renal tumors and trauma; however, massive nephron loss and persistent fibrosis readily lead to chronic kidney disease (CKD). Current therapeutic options remain non-curative and costly, as nearly half of PN patients inevitably progress to end-stage renal failure. Here, we present an innovative regenerative platform for PN-induced CKD, integrating structural biomimicry with targeted molecular inhibition. Harnessing light-based bioprinting of gelatin and hyaluronic acid methacrylates coupled with removable alginate microfiber, we constructed a hierarchical channel scaffold (HCS) that features precisely patterned macrochannels and template-derived microchannels, which closely mimics native kidney architecture, provides structural support, and remarkably enhances cell migration (∼5.45-fold) and rapid neovascularization (∼7.66-fold) over unidirectional channel structures. Moreover, interleukin 11 (IL11) was identified as a novel therapeutic target in kidney fibrosis after PN. Thus, extracellular vesicles (EVs) derived from mesenchymal stem cells loaded with IL11 small interfering RNA (siIL11) were homogeneously encapsulated into HCS, achieving over 4-fold higher renal retention than systemic delivery in PN-induced CKD mice. Furthermore, sustained local release of EV-siIL11 and hierarchically channeled HCS guided synergistic regenerative effects that remarkably inhibited fibrosis, cell cycle arrest, and immune responses, thereby potently preventing kidney atrophy and restoring renal structure with newly aligned nephrons and vasculature, ultimately recovering kidney function. Further analysis revealed that IL11 silencing reversed epithelial‒mesenchymal transition by suppressing the STAT3-ERK-GSK3β-SNAI1 axis. This topological multifunctional hydrogel platform offers a localized, sustained, and clinically translatable strategy for postsurgical kidney regeneration.
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BibTeX
@article{yu2026topologically,
title = {{A topologically engineered hydrogel platform targeting IL11 promotes renal repair after partial nephrectomy}},
author = {Zeming Yu and Xianhao Dong and Feiyi Li and Yanwen Zhang and Shuxin Dai and Ning Cao and Xiaopeng Jia and Jie Zhao and Bing Wang and Wenxiu Chang and Deling Kong and Yuebing Wang},
journal = {Bioactive materials},
year = {2026},
month = oct,
doi = {10.1016/j.bioactmat.2026.10.024},
url = {https://europepmc.org/article/PMC/PMC13717047},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - A topologically engineered hydrogel platform targeting IL11 promotes renal repair after partial nephrectomy
AU - Zeming Yu
AU - Xianhao Dong
AU - Feiyi Li
AU - Yanwen Zhang
AU - Shuxin Dai
AU - Ning Cao
AU - Xiaopeng Jia
AU - Jie Zhao
AU - Bing Wang
AU - Wenxiu Chang
AU - Deling Kong
AU - Yuebing Wang
PY - 2026
DA - 2026/10/22
JO - Bioactive materials
DO - 10.1016/j.bioactmat.2026.10.024
UR - https://europepmc.org/article/PMC/PMC13717047
AB - Partial nephrectomy (PN) is the gold standard for treating renal tumors and trauma; however, massive nephron loss and persistent fibrosis readily lead to chronic kidney disease (CKD). Current therapeutic options remain non-curative and costly, as nearly half of PN patients inevitably progress to end-stage renal failure. Here, we present an innovative regenerative platform for PN-induced CKD, integrating structural biomimicry with targeted molecular inhibition. Harnessing light-based bioprinting of gelatin and hyaluronic acid methacrylates coupled with removable alginate microfiber, we constructed a hierarchical channel scaffold (HCS) that features precisely patterned macrochannels and template-derived microchannels, which closely mimics native kidney architecture, provides structural support, and remarkably enhances cell migration (∼5.45-fold) and rapid neovascularization (∼7.66-fold) over unidirectional channel structures. Moreover, interleukin 11 (IL11) was identified as a novel therapeutic target in kidney fibrosis after PN. Thus, extracellular vesicles (EVs) derived from mesenchymal stem cells loaded with IL11 small interfering RNA (siIL11) were homogeneously encapsulated into HCS, achieving over 4-fold higher renal retention than systemic delivery in PN-induced CKD mice. Furthermore, sustained local release of EV-siIL11 and hierarchically channeled HCS guided synergistic regenerative effects that remarkably inhibited fibrosis, cell cycle arrest, and immune responses, thereby potently preventing kidney atrophy and restoring renal structure with newly aligned nephrons and vasculature, ultimately recovering kidney function. Further analysis revealed that IL11 silencing reversed epithelial‒mesenchymal transition by suppressing the STAT3-ERK-GSK3β-SNAI1 axis. This topological multifunctional hydrogel platform offers a localized, sustained, and clinically translatable strategy for postsurgical kidney regeneration.
SN - 2452-199X
ER -