Prevascularized Micro‑/Nano‑Sized Spheroid/Bead Aggregates for Vascular Tissue Engineering

Efficient strategies to promote microvascularization in vascular tissue engineering,a central priority in regenerative medicine,are still scarce;nano-and micro-sized aggregates and spheres or beads harboring primitive microvascular beds are promising methods in vascular tissue engineering.Capillaries are the smallest type and in numerous blood vessels,which are distributed densely in cardiovascular system.To mimic this microvascular network,specific cell components and proangiogenic factors are required.Herein,advanced biofabrication methods in microvascular engineering,including extrusion-based and droplet-based bioprinting,Kenzan,and biogripper approaches,are deliberated with emphasis on the newest works in prevascular nano-and micro-sized aggregates and microspheres/microbeads.

Noncoding RNAs and Their Potential Therapeutic Applications in Tissue Engineering

Tissue engineering is a relatively new but rapidly developing field in the medical sciences. Noncoding RNAs(ncRNAs) are functional RNA molecules without a protein-coding function; they can regulate cellular behavior and change the biological milieu of the tissue. The application of ncRNAs in tissue engineering is starting to attract increasing attention as a means of resolving a large number of unmet healthcare needs, although ncRNA-based approaches have not yet entered clinical practice. In-depth research on the regulation and delivery of ncRNAs may improve their application in tissue engineering.The aim of this review is: to outline essential ncRNAs that are related to tissue engineering for the repair and regeneration of nerve, skin, liver, vascular system, and muscle tissue; to discuss their regulation and delivery; and to anticipate their potential therapeutic applications.

Advances in the differentiation of pluripotent stem cells into vascular cells

Blood vessels constitute a closed pipe system distributed throughout the body,transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys.Changes in blood vessels are related to many disorders like stroke,myocardial infarction,aneurysm,and diabetes,which are important causes of death worldwide.Translational research for new appro-aches to disease modeling and effective treatment is needed due to the huge socio-economic burden on healthcare systems.Although mice or rats have been widely used,applying data from animal studies to human-specific vascular physiology and pathology is difficult.The rise of induced pluripotent stem cells(iPSCs)provides a reliable in vitro resource for disease modeling,regenerative medicine,and drug discovery because they carry all human genetic information and have the ability to directionally differentiate into any type of human cells.This review summarizes the latest progress from the establishment of iPSCs,the strategies for differentiating iPSCs into vascular cells,and the in vivo trans-plantation of these vascular derivatives.It also introduces the application of these technologies in disease modeling,drug screening,and regenerative medicine.Additionally,the application of high-tech tools,such as omics analysis and high-throughput sequencing,in this field is reviewed.

Cartilage oligomeric matrix protein enhances the vascularization of acellular nerves

Vascularization of acellular nerves has been shown to contribute to nerve bridging.In this study,we used a 10-mm sciatic nerve defect model in rats to determine whether cartilage oligomeric matrix protein enhances the vascularization of injured acellular nerves.The rat nerve defects were treated with acellular nerve grafting（control group） alone or acellular nerve grafting combined with intraperitoneal injection of cartilage oligomeric matrix protein（experimental group）.As shown through two-dimensional imaging,the vessels began to invade into the acellular nerve graft from both anastomotic ends at day 7 post-operation,and gradually covered the entire graft at day 21.The vascular density,vascular area,and the velocity of revascularization in the experimental group were all higher than those in the control group.These results indicate that cartilage oligomeric matrix protein enhances the vascularization of acellular nerves.

Construction of tissue-engineered vascular grafts with enhanced patency by integrating heparin,cell-adhesive peptide,and carbon monoxide nanogenerators into acellular blood vessels

Small-diameter tissue-engineered vascular grafts(sdTEVGs)have garnered significant attention as a potential treatment modality for vascular bypass grafting and replacement therapy.However,the intimal hyperplasia and thrombosis are two major complications that impair graft patency during transplantation.To address this issue,we fabricated the covalent-organic framework(COF)-based carbon monoxide(CO)nanogenerator-and co-immobilized with LXW-7 peptide and heparin to establish a multifunctional surface on TEVGs constructed from acellular blood vessels for preventing thrombosis and stenosis.The cell-adhesive peptide LXW-7 could capture endothelial-forming cells(EFCs)to promote endothelialization,while the antithrombotic molecule heparin prevented thrombus formation.The reactive oxygen species(ROS)-triggered CO release suppressed the adhesion and activation of macrophages,leading to the reduction of ROS and inflammatory factors.As a result,the endothelial-to-mesenchymal transition(EndMT)triggered by inflammation was restricted,facilitating the maintenance of the homeostasis of the neo-endothelium and preventing pathological remodeling in TEVGs.When transplanted in vivo,these vascular grafts exhibited negligible intimal hyperplasia and remained patent for 3 months.This achievement provided a novel approach for constructing antithrombotic and anti-hyperplastic TEVGs.

Novel magnetic silk fibroin scaffolds with delayed degradation for potential long-distance vascular repair

Although with the good biological properties,silk fibroin(SF)is immensely restrained in long-distance vascular defect repair due to its relatively fast degradation and inferior mechanical properties.It is necessary to construct a multifunctional composite scaffold based on SF.In this study,a novel magnetic SF scaffold(MSFCs)was prepared by an improved infiltration method.Compared with SF scaffold(SFC),MSFCs were found to have better crystallinity,magnetocaloric properties,and mechanical strength,which was ascribed to the rational introduction of iron-based magnetic nanoparticles(MNPs).Moreover,in vivo and in vitro experiments demonstrated that the degradation of MSFCs was significantly extended.The mechanism of delayed degradation was correlated with the dual effect that was the newly formed hydrogen bonds between SFC and MNPs and the complexing to tyrosine(Try)to inhibit hydrolase by internal iron atoms.Besides,theβ-crystallization of protein in MSFCs was increased with the rise of iron concentration,proving the beneficial effect after MNPS doped.Furthermore,although macrophages could phagocytose the released MNPs,it did not affect their function,and even a reasonable level might cause some cytokines to be upregulated.Finally,in vitro and in vivo studies demonstrated that MSFCs showed excellent biocompatibility and the growth promotion effect on CD34-labeled vascular endothelial cells(VECs).In conclusion,we confirm that the doping of MNPs can significantly reduce the degradation of SFC and thus provide an innovative perspective of multifunctional biocomposites for tissue engineering.