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Schisandra Lignans- and MSCs-Laden Microgels Attenuate Inflammation on LPS-Induced HepG2 Cells in a PEGNB Hydrogel Model

Xingdan Wang1,#, Lei Yang1,#, Renmeng Liu1, Yuheng Du1, Zhihuan Li1, Xinyue Zhang1, Linhao Zhu1, Ni Ren2,*
1 Department of Chemical Engineering, University of Science and Technology Liaoning, Anshan, China
2 Department of Applied Technology, University of Science and Technology Liaoning, Anshan, China
* Corresponding Author: Ni Ren. Email: email
# These authors contributed equality to this work
(This article belongs to the Special Issue: Polymer Materials for Tissue Engineering and Cell Encapsulation)

Journal of Polymer Materials https://doi.org/10.32604/jpm.2026.081663

Received 06 March 2026; Accepted 25 June 2026; Published online 20 July 2026

Abstract

Hepatitis has imposed a substantial burden on human health. Tumor necrosis factor-α (TNF-α) drives the inflammatory response by triggering downstream signaling, particularly the nuclear factor kappa B (NF-κB) pathway. Suppressing NF-κB activation represents a promising therapeutic strategy. PEGNB, a polymeric hydrogel, exhibits significant potential due to its superior cytocompatibility. We developed a controlled-delivery microgel platform by encapsulating Schisandra lignans (SLs) and mesenchymal stromal cells (MSCs) in polyethylene glycol-norbornene (PEGNB) microgels. To mimic an inflammatory hepatic microenvironment in vitro, Lipopolysaccharide (LPS)-induced HepG2 cells were encapsulated in bulk PEGNB hydrogel. The microgel–cell system enabled localized co-delivery of SLs and MSCs paracrine factors to LPS-induced cell-laden hydrogel constructs. SLs were extracted from Schisandra chinensis raw powder, yielding 0.83 mg/g of deoxyschisandrin and 2.51 mg/g of schisandrin. Based on the MTT assay, concentrations ≤ 5.6 μM were selected as a non-cytotoxic working range for subsequent in vitro studies. Microfluidic technology was used to fabricate PEGNB microgels with high monodispersity and diameters ranging from 130–170 μm. PEGNB-based microgels enabled the co-delivery of SLs and MSCs, serving as a polymeric platform for attenuating hepatic inflammatory responses while maintaining high cell viability above 70% and achieving sustained SLs release of 82.31 ± 4.35% over 14 days. In this model, SLs–MSC-laden microgels significantly reduced TNF-α and Interleukin-6 (IL-6) expression compared with untreated controls, and the combined SLs–MSC treatment produced a greater reduction than either SLs or MSCs alone. These results support PEGNB-based microgel co-delivery of SLs and MSCs as a promising strategy to attenuate inflammatory responses in an in vitro hepatic inflammation model.

Keywords

PEGNB hydrogel; mesenchymal stromal cells; microfluidics; hepatitis; anti-inflammation
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