Distinctive fish collagen drives vascular regeneration by polarizing macrophages to M2 phenotype via TNF-α/NF-κB pathway

Collagen is a structural protein that plays a critical role in tissue regeneration and is widely utilized in biomedical applications. Recent studies have demonstrated that collagen can modulate macrophage polarization; however, most studies have focused on mammalian collagen such as type I collagen derived from bovine and pig sources. In this study, we performed a comprehensive investigation of the role of collagen derived from aquatic sources, specifically fish swim bladder-derived collagen (SCC), in modulating macrophage inflammation using in vitro and in vivo experiments. First, collagen-coated and collagen-incorporated electrospun poly(ε-caprolactone) (PCL) films were prepared. RNA-Seq analysis showed that SCC could promote M0 and M1 phenotype macrophage transition into M2 through the activation of TNF-α/NF-κB and the downstream signaling pathways. Subcutaneous implantation and artery replacement were also performed. Moreover, SCC prolonged coagulation and synergistically reduces the risk of stenosis. Finally, mouse carotid artery replacement demonstrated that the SCC-modified vascular graft exhibited higher patency in combination with rapid endothelialization and reduced inflammatory responses in vivo. Taken together, we provided strong evidence that fish swim bladder-derived collagen has the capability to modulate macrophage polarization and shows great potential for tissue remodeling and regeneration.