3D environment with BMP-2-releasing nanocarriers enhances osteogenic commitment of human tendon stem cells

This study introduces a 3D bioprinted scaffold embedding human Bone Morphogenetic Protein-2 (hBMP-2)-loaded Poly-lactic-co-glycolic Acid nanocarriers (PLGA-NCs) to induce the osteogenic differentiation of human Tendon Stem/Progenitor Cells (TSPCs) harvested from tendon explants. The nanocarriers (120 ± 40 nm) were embedded in a Gelatin Methacryloyl (GelMA) matrix and bioplotted under optimized conditions to preserve cell viability (60%). A 3D dynamic culture system, supported by compartmental modelling, enabled continuous perfusion over 21 days, promoting efficient metabolite exchange and removal of catabolic byproducts. This environment enhanced proliferation and osteogenic differentiation, demonstrated by a 20-fold increase in osteopontin (p < 0.05) and an 8-fold increase in osteocalcin (p < 0.05) expression, along with increased calcium deposition observed via Alizarin Red S staining. In contrast, static monolayer cultures with soluble hBMP-2 (20 ng/mL) showed reduced osteogenic activity. These findings suggest that the engineered scaffold offers a promising strategy for regenerating the bone-tendon interface by leveraging the multipotency of TSPCs in a biomimetic 3D environment.