Degradable Scaffold-Mediated Synergistic Matrix Formation by Endogenous Cells: An In Vivo Manufacturing Strategy for Off-the-Shelf Cardiovascular Bypass Grafts to Address Clinical Shortages

Cardiovascular bypass surgery is an important treatment for severe atherosclerosis, but the scarcity of autologous blood vessels restricts its clinical application. Although tissue-engineered vascular grafts (TEVGs) have potential, the long cycle of traditional in vitro culture makes it difficult to achieve "off-the-shelf" supply. This study innovatively proposes a strategy of guiding the in vivo self-assembly of endogenous cells via degradable scaffolds to rapidly construct cardiovascular bypass grafts. After implanting electrospun PLCL nanofibrous elastomer scaffolds subcutaneously in SD rats, host fibroblasts, and abdominal adipose-derived stem cells were recruited in only two weeks. These cells synergistically secreted extracellular matrix, forming an endogenous cell-empowered tissue-engineered PLCL (TE-P) vascular graft. The graft has appropriate stress relaxation and creep properties, and can support the adhesion and migration of arterial endothelial cells. In the abdominal aorta replacement model, TE-P remained patent 90 days after transplantation, with the vessel wall having synchronous contraction function and elasticity, and the effect of tissue structure reconstruction was close to that of the "gold standard" autologous blood vessels. Transcriptome analysis showed that TE-P promotes vascular regeneration through the synergistic mechanisms of energy metabolism, immune balance, cell fate regulation, and matrix remodeling. This conclusion was verified by immunofluorescence, transmission electron microscopy, and flow cytometry. The scalable platform established in this study realizes the rapid in vivo manufacturing of off-the-shelf cardiovascular bypass grafts through the self-assembly of endogenous cells, making its production cycle match the time window of elective surgery, and providing a new solution to break through the bottleneck of clinical shortage of transplant vessels.