Biodegradable Inks in Indirect Three-Dimensional Bioprinting for Tissue Vascularization.

Mature vasculature is important for the survival of bioengineered tissue constructs, both in vivo and in vitro; however, the fabrication of fully vascularized tissue constructs remains a great challenge in tissue engineering. Indirect three-dimensional (3D) bioprinting refers to a 3D printing technique that can rapidly fabricate scaffolds with controllable internal pores, cavities, and channels through the use of sacrificial molds. It has attracted much attention in recent years owing to its ability to create complex vascular network-like channels through thick tissue constructs while maintaining endothelial cell activity. Biodegradable materials play a crucial role in tissue engineering. Scaffolds made of biodegradable materials act as temporary templates, interact with cells, integrate with native tissues, and affect the results of tissue remodeling. Biodegradable ink selection, especially the choice of scaffold and sacrificial materials in indirect 3D bioprinting, has been the focus of several recent studies. The major objective of this review is to summarize the basic characteristics of biodegradable materials commonly used in indirect 3D bioprinting for vascularization, and to address recent advances in applying this technique to the vascularization of different tissues. Furthermore, the review describes how indirect 3D bioprinting creates blood vessels and vascularized tissue constructs by introducing the methodology and biodegradable ink selection. With the continuous improvement of biodegradable materials in the future, indirect 3D bioprinting will make further contributions to the development of this field.

Three-dimensional bioprinting: A cutting-edge tool for designing and fabricating engineered living materials.

The design of engineered living materials (ELMs) is an emerging field developed from synthetic biology and materials science principles. ELMs are multi-scale bulk materials that combine the properties of self-healing and organism adaptability with the designed physicochemical or mechanical properties for functional applications in various fields, including therapy, electronics, and architecture. Among the many ELM design and manufacturing methods, three-dimensional (3D) bioprinting stands out for its precise control over the structure of the fabricated constructs and the spatial distribution of cells. In this review, we summarize the progress in the field, cell type and material selection, and the latest applications of 3D bioprinting to manufacture ELMs, as well as their advantages and limitations, hoping to deepen our understanding and provide new insights into ELM design. We believe that 3D bioprinting will become an important development direction and provide more contributions to this field.

Exosomes in Liquid Biopsy: A Nanotool for Postradiotherapy Cancer Monitoring.

Liquid biopsy has advantages over traditional biopsy, which cannot determine tumor dynamics. As a noninvasive and precise test, liquid biopsy detects biomarkers that carry information on tumor progression and has undergone tremendous development in recent years. Exosome detection is one of the methods of liquid biopsy. Radiotherapy affects the release of exosomes and intercellular communication. Based on the properties, extractability, and detectability of exosomes, key exosomal cargoes after tumor radiotherapy can be used as biomarkers for tumor prognosis. Exosomes after tumor radiotherapy can be used for liquid biopsy. The main applications include (1) predicting radiotherapy efficacy, (2) predicting tumor prognosis, and (3) optimizing the regimen of tumor treatment. This review provides further research directions for liquid biopsy after tumor radiotherapy.

Exosomes and ferroptosis: roles in tumour regulation and new cancer therapies.

Research on the biological role of exosomes is rapidly developing, and recent evidence suggests that exosomal effects involve ferroptosis. Exosomes derived from different tissues inhibit ferroptosis, which increases tumour cell chemoresistance. Therefore, exosome-mediated regulation of ferroptosis may be leveraged to design anticancer drugs. This review discusses three pathways of exosome-mediated inhibition of ferroptosis: (1) the Fenton reaction; (2) the ferroptosis defence system, including the Xc-GSH-GPX4 axis and the FSP1/CoQ10/NAD(P)H axis; and (3) lipid peroxidation. We also summarize three recent approaches for combining exosomes and ferroptosis in oncology therapy: (1) promoting exosome-inhibited ferroptosis to enhance chemotherapy; (2) encapsulating exosomes with ferroptosis inducers to inhibit cancers; and (3) developing therapies that combine exosomal inhibitors and ferroptosis inducers. This review will contribute toward establishing effective cancer therapies.

Irradiated Cell-Derived Exosomes Transmit Essential Molecules Inducing Radiation Therapy Resistance.

Radioresistance has always been a major obstacle in radiation therapy (RT) progress. Radiation therapy (RT) leads to changes in the contents of released exosomes. Research has shown that irradiated cell-derived exosomes influence recipient cell proliferation, migration, cell cycle arrest, and apoptosis. All evidence indicates that exosomes play a significant role in radioresistance. In this review, we describe the potential role of exosomes in cancer. We summarize that the irradiated cell-derived exosomes influence radioresistance in recipient cells by 3 main mechanisms: (1) enhancing DNA repair, (2) regulating cell death signaling pathways, and (3) inducing cancer cells to exhibit stem cell properties. We also discuss that the origin of the phenomenon might be the changes of molecular mechanisms of irradiated cell-derived exosomes formation affected by RT. Further, targeting exosomes as an adjuvant therapy might be a promising way for cancer treatments.

Copper-containing titanium alloys promote angiogenesis in irradiated bone through releasing copper ions and regulating immune microenvironment.

Poor vascularization was demonstrated as a factor inhibiting bone regeneration in patients receiving radiotherapy. Various copper-containing materials have been reported to increase angiogenesis, therefore might improve bone formation. In this study, a Ti6Al4V-1.5Cu alloy was prepared using selective laser melting (SLM) technology. The immunomodulatory and pro-angiogenic effects of the Ti6Al4V-1.5Cu alloys were examined. In vitro, Ti6Al4V-1.5Cu stimulated vascular formation by restraining inflammatory factors and provoking angiogenic factors in non-irradiated and irradiated macrophages. In vivo, the angiogenic effects of the Ti6Al4V-1.5Cu alloy were confirmed using an irradiated rat femur defect model. Moreover, we found that the biological effects of the Ti6Al4V-1.5Cu alloy were partially due to the release of copper ions and associated with PI3K-Akt signaling pathway. In conclusion, this study indicated the potential of the Ti6Al4V-1.5Cu alloy to promote angiogenesis by releasing copper ions and inhibiting inflammation in normal and irradiated tissues.

Exosomes derived from plasma: promising immunomodulatory agents for promoting angiogenesis to treat radiation-induced vascular dysfunction.

Ionizing radiation (IR)-induced vascular disorders slow down tissue regeneration. Exosomes derived from plasma exhibit potential to promote angiogenesis; meanwhile, the immune microenvironment plays a significant role in the process. This study aimed to test the hypothesis that plasma exosomes promote angiogenesis in irradiated tissue by mediating the immune microenvironment. First, we explored the impact of IR on macrophages. We found that cell viability and capacity for promoting angiogenesis were decreased in irradiated macrophages compared to control macrophages. Then, we isolated and characterized rat plasma-derived exosomes (RP-Exos) which were defined as 40-160 nm extracellular vesicles extracted from rat plasma. Afterward, we evaluated the effects of RP-Exos on the behaviors of irradiated macrophages. Our results show that RP-Exos promoted cell proliferation. More importantly, we found that RP-Exos stimulated the immune microenvironment in a manner that improved the angiogenesis-related genes and proteins of irradiated macrophages. The supernatant of macrophage cell cultures was used as conditioned medium to treat human primary umbilical vein endothelial cells, further confirming the pro-angiogenic ability of macrophages receiving RP-Exo intervention. RP-Exos were used in vivo to treat irradiated skin or calvarial defects in irradiated Sprague-Dawley male rats. The results indicated the ability of RP-Exos to enhance angiogenesis and promote tissue regeneration. Our research suggested the potential of plasma exosomes to be used as immunomodulatory agents with angiogenic capacity to treat radiation-associated vascular disorders and facilitate tissue repair.