Giordano Perini, Antonio Minopoli, Giada Di Giulio, Margherita Montescagli, Alberto Augello, Valeria Ferrara, Davide Evangelista, Matteo Marras, Giulia Artemi, Anna Amelia Caretto, Stefano Gentileschi, Dania Nachira, Dario Zambrano, Sana Munir, Valerio Pontecorvi, Cristiano Spada, Loredana Gualtieri, Andreas Rosenkranz, Valentina Palmieri, Ivo Boskoski, Marco De Spirito, Massimiliano Papi
Intestinal disorders such as inflammatory bowel diseases (IBD) and gastrointestinal fistulae (GIFs) are marked by chronic inflammation, barrier dysfunction, and impaired repair, conditions insufficiently addressed by current treatments. Regenerative strategies able to restore epithelial integrity and support stromal and vascular remodeling are therefore highly needed. The stromal vascular fraction (SVF), a heterogeneous and autologous cell population from adipose tissue, offers angiogenic, immunomodulatory, and regenerative properties, while three-dimensional (3D) bioprinting enables its embedding in hydrogels to enhance survival and activity. MXenes (MX), a novel class of two-dimensional materials, can help to add further advantages through their bioactive, antioxidant, and pro-angiogenic features. In this contribution, we engineered 3D bioprinted constructs composed of SVF embedded in GelMA functionalized with MX. After confirming the biocompatibility of MX on multiple cell types, we demonstrated that SVF MX constructs notably promoted wound closure, endothelial tube formation, and epithelial proliferation, while maintaining stable, non-toxic ROS levels and demonstrating excellent cytocompatibility[GP1.1]. These findings highlight MX-enriched SVF constructs as an innovative platform for next-generation regenerative therapies, combining the autologous, low-immunogenic profile of SVF with the multifunctional properties of MX to address complex intestinal disorders.