Search for: All records

Abstract In oxygen (O₂)‐controlled cell culture, an indispensable tool in biological research, it is presumed that the incubator setpoint equals the O₂tension experienced by cells (i.e., pericellular O₂). However, it is discovered that physioxic (5% O₂) and hypoxic (1% O₂) setpoints regularly induce anoxic (0% O₂) pericellular tensions in both adherent and suspension cell cultures. Electron transport chain inhibition ablates this effect, indicating that cellular O₂consumption is the driving factor. RNA‐seq analysis revealed that primary human hepatocytes cultured in physioxia experience ischemia‐reperfusion injury due to cellular O₂consumption. A reaction‐diffusion model is developed to predict pericellular O₂tension a priori, demonstrating that the effect of cellular O₂consumption has the greatest impact in smaller volume culture vessels. By controlling pericellular O₂tension in cell culture, it is found that hypoxia vs. anoxia induce distinct breast cancer transcriptomic and translational responses, including modulation of the hypoxia‐inducible factor (HIF) pathway and metabolic reprogramming. Collectively, these findings indicate that breast cancer cells respond non‐monotonically to low O₂, suggesting that anoxic cell culture is not suitable for modeling hypoxia. Furthermore, it is shown that controlling atmospheric O₂tension in cell culture incubators is insufficient to regulate O₂in cell culture, thus introducing the concept of pericellular O₂‐controlled cell culture. 

Abstract Solid tumors are protected from antitumor immune responses due to their hypoxic microenvironments. Weakening hypoxia‐driven immunosuppression by hyperoxic breathing of 60% oxygen has shown to be effective in unleashing antitumor immune cells against solid tumors. However, efficacy of systemic oxygenation is limited against solid tumors outside of lungs and has been associated with unwanted side effects. As a result, it is essential to develop targeted oxygenation alternatives to weaken tumor hypoxia as novel approaches to restore immune responses against cancer. Herein, injectable oxygen‐generating cryogels (O₂‐cryogels) to reverse tumor‐induced hypoxia are reported. These macroporous biomaterials are designed to locally deliver oxygen, inhibit the expression of hypoxia‐inducible genes in hypoxic melanoma cells, and reduce the accumulation of immunosuppressive extracellular adenosine. The data show that O₂‐cryogels enhance T cell‐mediated secretion of cytotoxic proteins, restoring the killing ability of tumor‐specific cytotoxic T lymphocytes, both in vitro and in vivo. In summary, O₂‐cryogels provide a unique and safe platform to supply oxygen as a coadjuvant in hypoxic tumors and have the potential to improve cancer immunotherapies. 

Abstract Cardiovascular diseases (CVDs) are known as the major cause of death worldwide. In spite of tremendous advancements in medical therapy, the gold standard for CVD treatment is still transplantation. Tissue engineering, on the other hand, has emerged as a pioneering field of study with promising results in tissue regeneration using cells, biological cues, and scaffolds. 3D bioprinting is a rapidly growing technique in tissue engineering because of its ability to create complex scaffold structures, encapsulate cells, and perform these tasks with precision. More recently, 3D bioprinting has made its debut in cardiac tissue engineering, and scientists are investigating this technique for development of new strategies for cardiac tissue regeneration. In this review, the fundamentals of cardiac tissue biology, available 3D bioprinting techniques and bioinks, and cells implemented for cardiac regeneration are briefly summarized and presented. Afterward, the pioneering and state‐of‐the‐art works that have utilized 3D bioprinting for cardiac tissue engineering are thoroughly reviewed. Finally, regulatory pathways and their contemporary limitations and challenges for clinical translation are discussed. 

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has led to an unprecedented global health crisis, resulting in a critical need for effective vaccines that generate protective antibodies. Protein subunit vaccines represent a promising approach but often lack the immunogenicity required for strong immune stimulation. To overcome this challenge, it is first demonstrated that advanced biomaterials can be leveraged to boost the effectiveness of SARS‐CoV‐2 protein subunit vaccines. Additionally, it is reported that oxygen is a powerful immunological co‐adjuvant and has an ability to further potentiate vaccine potency. In preclinical studies, mice immunized with an oxygen‐generating coronavirus disease 2019 (COVID‐19) cryogel‐based vaccine (O₂‐Cryogel_VAX) exhibit a robust Th1 and Th2 immune response, leading to a sustained production of highly effective neutralizing antibodies against the virus. Even with a single immunization, O₂‐Cryogel_VAXachieves high antibody titers within 21 days, and both binding and neutralizing antibody levels are further increased after a second dose. Engineering a potent vaccine system that generates sufficient neutralizing antibodies after one dose is a preferred strategy amid vaccine shortage. The data suggest that this platform is a promising technology to reinforce vaccine‐driven immunostimulation and is applicable to current and emerging infectious diseases.