3D-Bioprinting of Stromal Vascular Fraction for Gastrointestinal Regeneration.

Abstract

Intestinal disorders such as inflammatory bowel diseases (IBDs), Crohn's disease, malabsorption syndromes, and gastrointestinal fistulae (GIFs) are often characterized by chronic inflammation, epithelial barrier disruption, impaired stromal remodeling, and defective angiogenesis. These multifactorial alterations hinder tissue repair and contribute to poor clinical outcomes, with limited efficacy from current therapeutic options. Despite recent advances in surgical and endoscopic techniques, current treatment options remain limited and are frequently accompanied by high morbidity and costs. In this context, regenerative medicine offers a promising avenue to support tissue repair and improve patient care Regenerative medicine offers a promising avenue to restore intestinal homeostasis using advanced biomaterials and cell-based therapies. In this study, we developed a 3D-bioprinted model based on patient-derived stromal vascular fraction (SVF) embedded in a GelMA hydrogel, designed to promote intestinal tissue regeneration. To identify the most suitable hydrogel for bioprinting, we initially evaluated the mechanical properties and biocompatibility of four distinct matrices using bone marrow-derived mesenchymal stromal cells (BM-MSCs). Among the tested formulations, GelMA demonstrated optimal support for cell viability, low oxidative stress, and structural stability in physiologically relevant conditions. Based on these results, GelMA was selected for subsequent bioprinting of freshly isolated SVF. The resulting bioprinted constructs enhanced key regenerative processes across multiple compartments. The SVF-laden constructs significantly enhanced intestinal epithelial cell viability and tight junction formation, as shown by increased trans-epithelial electrical resistance (TEER). Co-culture with fibroblasts accelerated wound closure, while endothelial cells exhibited increased tube formation in the presence of SVF. Together with VEGF secretion, indicating strong paracrine and angiogenic effects. By supporting epithelial, stromal, and vascular regeneration, this approach provides a versatile and translational platform for treating a broad spectrum of intestinal pathologies.