Engineering synthetic erythrocytes for blood substitution

Blood shortages are a common occurrence in hospitals worldwide. Situations of war, natural disasters, pandemics, or lack of donors can rapidly disrupt the supply-demand of blood, leading to delays in life-saving treatments. To solve this problem, blood substitutes have been extensively researched, having become progressively more complex in functionality over the years. However, the replication of the function attributed to erythrocytes, the main cellular component of blood, has remained minimal. This thesis delves into the field of erythrocyte engineering, providing an in-depth analysis of the structure and function of erythrocytes, the importance of fully synthetic erythrocytes in blood substitution, and the experimental process of engineering a fully synthetic erythrocyte. The state-of-the-art of the field is reviewed, as well as ethical challenges and fabrication techniques. A new, complex, oxygen-generating erythrocyte is presented from a bottom-up approach, including i) the production and development of safe-to-inject microparticles, ii) the development of synthetic erythrocyte membranes based on lipid coatings, and iii) the final combination of microparticles, lipid coatings, and functional nanomaterials to form a synthetic erythrocyte. The thesis is finalized with an outlook on the results of this work, recommendations for future developments, and secondary achievements with promising applicability in nanomedicine.