ArticleAdvanced healthcare materials2026
siRNA Delivery via Cross-Linked Gelatin Microparticles Enables Targeted Modulation of Osteogenic-Vascular Cross-Talk: An Advanced Human 3D in Vitro Test System for Therapeutic siRNA.
Article in Advanced healthcare materials, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Small interfering RNAs (siRNAs) have drawn particular attention for their ability to transiently and sequence-specifically silence target genes, not only for systemic but also for localized application. For bone regeneration, targeting inhibitory regulators by siRNAs offers opportunities to improve osteogenic-angiogenic coupling. Conventional experimental models often oversimplify this interaction as they fail to capture these multicellular tissue dynamics. To address this, we established a human three-dimensional co-culture model composed of osteogenic and vascular microtissues embedded in fibrin hydrogels to investigate siRNA effects on microtissue interaction. Local siRNA delivery to microtissues was achieved by oligomer-stabilized calcium phosphate nanoparticles (CaP-NP) loaded onto cross-linked gelatin microparticles (cGM). siRNA/CaP-NP-loaded cGM were assembled with human mesenchymal stem cells (hMSCs) to microtissues. This approach was demonstrated by silencing two antagonists with distinct expression profiles: Chordin, a low-abundance BMP inhibitor, and WWP-1, a highly expressed E3 ligase. Only Chordin siRNA improved the osteogenic-vascular cross-talk, whereas WWP-1 siRNA effects were limited to osteogenic effects. Next-generation sequencing (NGS) supported these results. We demonstrate that this co-culture platform permits systematic investigation of siRNA-mediated modulation of osteogenic-endothelial interactions, offering a relevant human model for preselecting therapeutic siRNA targets to advance vascularized bone tissue regeneration.
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