Emerging blood substitutes in emergency medicine: engineering erythrocytes to overcome scarcity

Trauma and substantial blood loss are major causes of mortality in emergency settings, underscoring the need for rapid blood replacement to stabilize patients. The global shortage of blood significantly disrupts health care, prompting scientists to explore synthetic blood substitutes to address issues related to allogenic blood transfusions, including the decline in voluntary donors and disease transmission risks. Recent research has focused on enhancing blood supplies through various substitutes, such as hemoglobin-based oxygen carriers and perfluorocarbons, with limited success. This review evaluates the biological structure and functions of these substitutes, exploring the methodologies involved in their fabrication. It discusses strategies for recreating the size, shape, and deformability of red blood cells through innovative particle design. This review discusses advances in engineered erythrocytes (EEs) and categorizes approaches into natural, synthetic, and hybrid methods, examining their safety and scalability as well as the implementation of nanotechnology to replicate the functional capabilities of natural EEs. Additionally, it evaluates the biological characteristics of these substitutes, and the techniques used to replicate the size, shape, and functionality of natural red blood cells through innovative design and synthetic biology. In emergency settings, artificial blood could provide critical support for patients awaiting compatible donor blood or undergoing surgical stabilization.