The use of human cells for the construction of 3D organ models in vitro based on cell self-assembly and engineering design has recently increased in popularity in the field of biological science. Although the organoids are able to simulate the structures and functions of organs in vitro, the 3D models have difficulty in forming a complex vascular network that can recreate the interaction between tissue and vascular systems. Therefore, organoids are unable to survive, due to the lack of oxygen and nutrients, as well as the accumulation of metabolic waste. Organoids-on-a-chip provides a more controllable and favorable design platform for co-culture of different cells and tissue types in organoid systems, overcoming some of the limitations present in organoid culture. However, the majority of them has vascular networks that are not adequately elaborate to simulate signal communications between bionic microenvironment (e.g., fluid shear force) and multiple organs. Here, we will review the technological progress of the vascularization in organoids and organoids-on-a-chip and the development of intravital 3D and 4D bioprinting as a new way for vascularization, which can aid in further study on tissue or organ development, disease research and regenerative medicine.

During myocardial infarction, microcirculation disturbance in the ischemic area can cause necrosis and formation of fibrotic tissue, potentially leading to malignant arrhythmia and myocardial remodeling. Here, we report a microchanneled hydrogel suture for two-way signal communication, pumping drugs on demand, and cardiac repair. After myocardial infarction, our hydrogel suture monitors abnormal electrocardiogram through the mobile device and triggers nitric oxide on demand via the hydrogel sutures’ microchannels, thereby inhibiting inflammation, promoting microvascular remodeling, and improving the left ventricular ejection fraction in rats and minipigs by more than 60% and 50%, respectively. This work proposes a suture for bidirectional communication that acts as a cardio-patch to repair myocardial infarction, that remotely monitors the heart, and can deliver drugs on demand.

There is no effective and noninvasive solution for thrombolysis because the mechanism by which certain thrombi become tissue plasminogen activator (tPA)-resistant remains obscure. Endovascular thrombectomy is the last option for these tPA-resistant thrombi, thus a new noninvasive strategy is urgently needed. Through an examination of thrombi retrieved from stroke patients, we found that neutrophil extracellular traps (NETs), ε-(γ-glutamyl) lysine isopeptide bonds and fibrin scaffolds jointly comprise the key chain in tPA resistance. A theranostic platform is designed to combine sonodynamic and mechanical thrombolysis under the guidance of ultrasonic imaging. Breakdown of the key chain leads to a recanalization rate of more than 90% in male rat tPA-resistant occlusion model. Vascular reconstruction is observed one month after recanalization, during which there was no thrombosis recurrence. The system also demonstrates noninvasive theranostic capabilities in managing pigs’ long thrombi (>8 mm) and in revascularizing thrombosis-susceptible tissue-engineered vascular grafts, indicating its potential for clinical application. Overall, this noninvasive theranostic platform provides a new strategy for treating tPA-resistant thrombi.

Tissue-engineered vascular grafts (TEVGs) have enormous potential for vascular replacement therapy. However, thrombosis and intimal hyperplasia are important problems associated with TEVGs especially small diameter TEVGs (<6 mm) after transplantation. Endothelialization of TEVGs is a key point to prevent thrombosis. Here, we discuss different types of endothelialization and different seed cells of tissue-engineered vascular grafts. Meanwhile, endothelial heterogeneity is also discussed. Based on it, we provide a new perspective for selecting suitable types of endothelialization and suitable seed cells to improve the long-term patency rate of tissue-engineered vascular grafts with different diameters and lengths.

The transplant of small‐diameter tissue engineering blood vessels (small‐diameter TEBVs) (<6 mm) in vascular replacement therapy often fails because of early onset thrombosis and long‐standing chronic inflammation. The specific inflammation state involved in small‐diameter TEBVs transplants remains unclear, and whether promoting inflammation resolution would be useful for small‐diameter TEBVs therapy need study. The neural protuberant orientation factor 1 (Netrin‐1) is found present in endothelial cells of natural blood vessels and has anti‐inflammatory effects. This work generates netrin‐1‐modified small‐diameter TEBVs by using layer‐by‐layer self‐assembly to resolve the inflammation. The results show that netrin‐1 reprograms macrophages (MΦ) to assume an anti‐inflammatory phenotype and promotes the infiltration and subsequent efflux of MΦ from inflamed sites over time, which improves the local microenvironment and the function of early homing endothelial progenitor cells (EPCs). Small‐diameter TEBVs modified by netrin‐1 achieve endothelialization after 30 d and retain patency at 14 months. These findings suggest that promoting the resolution of inflammation in time is necessary to induce endothelialization of small‐diameter TEBVs and prevent early thrombosis and problems associated with chronic inflammation. Furthermore, this work finds that the MΦ‐derived exosomes can target and regulate EPCs, which may serve as a useful treatment for other inflammatory diseases.