The formation of the complex and fully functional vascular networks in pivotal organs is a key challenge in tissue engineering research. Functional blood vessels not only maintain oxygen and nutrient delivery but also effectively get rid of waste. Recently, a deep understanding of the vascular tissue structure and tissue microenvironment helps to make several great progress in the construction of highly complex and biomimetic vascularized tissues and organs, using biomaterials such as hydrogels and biomaterial composites. In this review, we summarized the advantages and research progress of biomaterials used in constructing the vascularized tissue in tissue engineering regeneration, ischemic fibrosis, and so on. We also discussed the progression of vascularization in organs and organoids. First, we discuss the applications of biomaterial-based vascularized tissue in bone, skin, and other tissue regeneration. Secondly, we discussed biomaterials and their components in promoting vascularization of ischemic fibrosis organs such as cerebral infarction, myocardial infarction, and renal fibrosis. In addition, we also introduced the strategies and applications that biomaterials function as a biomimetic extracellular matrix performed to construct vascularized tissues or organs in vitro. Finally, coming opportunities and challenges are also discussed and commented on.

Rapid integration into the host tissue is critical for long-term patency after small diameter tissue engineering vascular grafts (sdTEVGs) transplantation. Neural recognition may be required for host integration and functionalization of the graft. However, immune rejection and inflammation hinder nerve regeneration of sdTEVGs. Here, a CRISPR/dCas9-nanocarrier was used for targeted programming of regulatory T cells (Treg cells) in situ to promote nerve regeneration of sdTEVGs by preventing excessive inflammation. Treg cells and (C-C chemokine receptor) CCR2+ macrophage recruitment occurred after transplantation. The nanodelivery system upregulated ten eleven translocation (TET2) in Treg cells in vitro. Reprogrammed Treg cells upregulated anti-inflammatory cytokines and decreased the proportion of CCR2+ macrophages. IL-6 concentrations decreased to the levels required for nerve regeneration. Implantation of CRISPR/dCas9 nanodelivery system-modified sdTEVGs in rats resulted in Treg cell editing, control of excessive inflammation, and promoted nerve regeneration. After 3 months, nerve regeneration was similar to that observed in normal blood vessels; good immune homeostasis, consistency of hemodynamics, and matrix regeneration were observed. Neural recognition promotes further integration of the graft into the host, with unobstructed blood vessels without intimal hyperplasia. Our findings provide new insights into vascular implant functionalization by the host.

Calcification of autologous pathological vessels and tissue engineering blood vessels (TEBVs) is a thorny problem in clinic. However, there is no effective and noninvasive treatment that is available against the calcification of TEBVs and autologous pathological vessels. Gli1 + cells are progenitors of smooth muscle cells (SMCs) and can differentiate into osteoblast-like cells, leading to vascular calcification. Our results showed that the spatiotemporal distribution of Gli1 + cells in TEBVs was positively correlated with the degree of TEBV calcification. An anticalcification approach was designed consisting of exosomes derived from mesenchymal stem cells delivering lncRNA-ANCR to construct the engineered exosome-Ancr/E7-EXO. The results showed that Ancr/E7-EXO effectively targeted Gli1 + cells, promoting rapid SMC reconstruction and markedly inhibiting Gli1 + cell differentiation into osteoblast-like cells. Moreover, Ancr/E7-EXO significantly inhibited vascular calcification caused by chronic kidney disease. Therefore, Ancr/E7-EXO reprogrammed Gli1 + cells to prevent calcification of vascular graft and autologous pathological vessel, providing unique insights for an effective anticalcification.