3D-bioprinted cell-laden blood vessel with dual drug delivery nanoparticles for advancing vascular regeneration

Abstract

Vascular regeneration plays a critical role in the treatment of cardiovascular diseases and in tissue engineering applications. In this study, we fabricated and characterized statin/curcumin-loaded nanoparticles for potential applications in vascular regeneration. The nanoparticles exhibited consistent spherical shape and sizes, indicating reproducibility and stability of the fabrication process. The sustained release of the loaded drugs from the nanoparticles indicated their suitability for controlled and prolonged drug delivery. Biocompatibility assessments revealed that the nanoparticles were nontoxic even at high concentrations and over extended periods. Moreover, the incorporation of statin within the nanoparticles enhanced the proliferative capacity and functional abilities of endothelial progenitor cells, thereby promoting angiogenesis and vascular repair. Co-administration of curcumin with statin further augmented the therapeutic effects by reducing intracellular reactive oxygen species levels and providing antioxidant protection against oxidative stress. Furthermore, we successfully integrated these nanoparticles into artificial blood vessels (ABVs) using three-dimensional printing technology, creating customizable constructs capable of supporting vascular regeneration. The viability and proliferative capacity of cells within the ABVs were preserved, which has potential for targeted drug delivery and localized therapy. In in vivo models of hindlimb ischemia, transplantation of nanoparticle-loaded ABVs resulted in significant improvements in terms of recovery speed and blood flow. Histological analysis confirmed the enhanced expression of vascular-related markers, indicating improved angiogenesis. Collectively, our findings demonstrate the potential of statin/curcumin-loaded nanoparticles as a promising approach for vascular tissue engineering and regenerative medicine. These nanoparticles offer controlled drug delivery, biocompatibility, and enhanced regenerative properties, suggesting that they are valuable tools for promoting vascular regeneration and advancing therapeutic interventions for cardiovascular diseases. Further research is required to fully elucidate the mechanisms of action and optimize their clinical applications.