Oxygen plays a critical role in human embryogenesis, homeostasis, and tissue regeneration. This review explores the biological relevance of oxygen at the cellular and tissue levels, emphasizing the importance of controlled delivery via engineered biomaterials and devices. Recent advances and future trends in oxygen delivery for tissue engineering are discussed, focusing on tissue-engineered constructs that can meet metabolic demands to facilitate regeneration. Oxygen is essential for cellular energy production and is transported from the lungs to tissues via hemoglobin. However, engineered tissues face challenges in maintaining adequate oxygen supply due to limited vascularization and diffusion limitations. To address this, oxygen-generating biomaterials and devices are being developed to provide a controlled oxygen supply. For example, tissue scaffolds functionalized with peroxides and perfluorocarbons have shown prolonged oxygen delivery (>12 days in vitro). Hemoglobin-based oxygen carriers (HBOCs) have been investigated as blood substitutes, but many initial HBOCs suffered from toxicity and side effects. Recent advances include the use of HBOCs to promote wound healing, particularly for diabetic ulcers. Globin-modified biomaterials have also been tested for neuroprotective and regenerative potential in preclinical models. Myoglobin, another hemoprotein, has higher oxygen affinity than hemoglobin and can be used for oxygen storage in bioengineered tissues. Neuroglobin, a newly discovered globin, has been shown to protect the brain and nervous system from hypoxia and oxidative stress. Enzyme systems modulating oxygen delivery, such as SOD and CAT, help clear reactive oxygen species (ROS) and facilitate oxygen transport. Exogenous enzymes from bacteria, archaea, and plants have also been explored for oxygen delivery to hypoxic tissues. Biomaterials and devices for oxygen generation and perfusion include peroxides, perfluorocarbons, and nanobubbles. These materials can be encapsulated or modified to control oxygen release kinetics. For example, perfluorocarbons have high oxygen solubility and are used as oxygen carriers in tissue engineering. Nanobubbles, when integrated into engineered scaffolds, can provide sustained oxygen release. The review highlights the importance of balancing oxygen delivery to meet cellular demands while avoiding hypoxia and hyperoxia. Future research should focus on optimizing oxygen delivery systems to improve tissue regeneration and clinical applications.Oxygen plays a critical role in human embryogenesis, homeostasis, and tissue regeneration. This review explores the biological relevance of oxygen at the cellular and tissue levels, emphasizing the importance of controlled delivery via engineered biomaterials and devices. Recent advances and future trends in oxygen delivery for tissue engineering are discussed, focusing on tissue-engineered constructs that can meet metabolic demands to facilitate regeneration. Oxygen is essential for cellular energy production and is transported from the lungs to tissues via hemoglobin. However, engineered tissues face challenges in maintaining adequate oxygen supply due to limited vascularization and diffusion limitations. To address this, oxygen-generating biomaterials and devices are being developed to provide a controlled oxygen supply. For example, tissue scaffolds functionalized with peroxides and perfluorocarbons have shown prolonged oxygen delivery (>12 days in vitro). Hemoglobin-based oxygen carriers (HBOCs) have been investigated as blood substitutes, but many initial HBOCs suffered from toxicity and side effects. Recent advances include the use of HBOCs to promote wound healing, particularly for diabetic ulcers. Globin-modified biomaterials have also been tested for neuroprotective and regenerative potential in preclinical models. Myoglobin, another hemoprotein, has higher oxygen affinity than hemoglobin and can be used for oxygen storage in bioengineered tissues. Neuroglobin, a newly discovered globin, has been shown to protect the brain and nervous system from hypoxia and oxidative stress. Enzyme systems modulating oxygen delivery, such as SOD and CAT, help clear reactive oxygen species (ROS) and facilitate oxygen transport. Exogenous enzymes from bacteria, archaea, and plants have also been explored for oxygen delivery to hypoxic tissues. Biomaterials and devices for oxygen generation and perfusion include peroxides, perfluorocarbons, and nanobubbles. These materials can be encapsulated or modified to control oxygen release kinetics. For example, perfluorocarbons have high oxygen solubility and are used as oxygen carriers in tissue engineering. Nanobubbles, when integrated into engineered scaffolds, can provide sustained oxygen release. The review highlights the importance of balancing oxygen delivery to meet cellular demands while avoiding hypoxia and hyperoxia. Future research should focus on optimizing oxygen delivery systems to improve tissue regeneration and clinical applications.