A topologically engineered hydrogel platform targeting IL11 promotes renal repair after partial nephrectomy
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Updated: Oct 31, 2026
Microdissection of Primary Renal Tissue Segments and Incorporation with Novel Scaffold-free Construct Technology
Published on: March 27, 2018
Zeming Yu1, Xianhao Dong2, Feiyi Li2
1School of Medicine, Institute of Transplant Medicine, Department of Surgical Intensive Care Unit, 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.
