Oxygen plays a crucial role in human embryogenesis, homeostasis, and tissue regeneration. The review explores the biological relevance of oxygen at both cellular and tissue levels, emphasizing the importance of controlled oxygen delivery via engineered biomaterials and devices. Recent advances and future trends in tissue-engineered constructs that can meet metabolic demands to facilitate regeneration are discussed. The challenges of ensuring mass transport of nutrients and molecular oxygen to cells in engineered tissues are highlighted, particularly the issue of oxygen tension decreasing towards the center of the graft or bioscaffold, leading to hypoxia and necrosis. Efforts to mimic the vascular network and integrate with host tissue are crucial for effective oxygen distribution and nutrient exchange. The review also covers the development of oxygen-generating biomaterials and devices, such as peroxides and perfluorocarbons, which can provide sustained oxygen delivery. Biological molecules like hemoglobin, myoglobin, neuroglobin, and enzymes that modulate oxygen delivery are explored, along with their potential in tissue engineering. The role of ROS in cell signaling and pathology is discussed, and the mechanisms of oxygen delivery from secondary materials, including nanobubbles and hydrogels, are analyzed. The review concludes by discussing oxygen-perfusing and oxygen-generating devices, such as bioreactors and microfluidic systems, which play a vital role in supporting tissue engineering and regenerative medicine.Oxygen plays a crucial role in human embryogenesis, homeostasis, and tissue regeneration. The review explores the biological relevance of oxygen at both cellular and tissue levels, emphasizing the importance of controlled oxygen delivery via engineered biomaterials and devices. Recent advances and future trends in tissue-engineered constructs that can meet metabolic demands to facilitate regeneration are discussed. The challenges of ensuring mass transport of nutrients and molecular oxygen to cells in engineered tissues are highlighted, particularly the issue of oxygen tension decreasing towards the center of the graft or bioscaffold, leading to hypoxia and necrosis. Efforts to mimic the vascular network and integrate with host tissue are crucial for effective oxygen distribution and nutrient exchange. The review also covers the development of oxygen-generating biomaterials and devices, such as peroxides and perfluorocarbons, which can provide sustained oxygen delivery. Biological molecules like hemoglobin, myoglobin, neuroglobin, and enzymes that modulate oxygen delivery are explored, along with their potential in tissue engineering. The role of ROS in cell signaling and pathology is discussed, and the mechanisms of oxygen delivery from secondary materials, including nanobubbles and hydrogels, are analyzed. The review concludes by discussing oxygen-perfusing and oxygen-generating devices, such as bioreactors and microfluidic systems, which play a vital role in supporting tissue engineering and regenerative medicine.