Ctrl + P: Blood

Dear Impossible Readers,

Global demand for blood continues to rise, driven by ageing populations, complex surgeries, and cancer treatments. The WHO estimates that over 40 per cent of global blood donations originate from just 16 per cent of the world’s population. Regular donors are ageing, and younger generations donate less frequently. Competing demands from plasma centres increase pressure. Maintaining a motivated, voluntary donor base is becoming a significant public health challenge worldwide. Donation rates fluctuate during holidays, pandemics, and crises. In many developing countries, hospitals receive only a fraction of the blood they require each year.

Matching donor and recipient blood types involves more than just the ABO system. For people with rare phenotypes such as Rh-null or Bombay, finding a compatible donor can take weeks. Maintaining rare-donor registries and cold-chain storage is costly and logistically challenging. Every donation must be tested for transfusion-transmissible infections like HIV, hepatitis B/C, and syphilis. Low-resource regions often lack the latest screening tools, creating safety gaps. Emerging pathogens require testing protocols to adapt continuously. Blood must be collected, processed, tested, stored, and transported under strict temperature control. Power outages, transport delays, or refrigeration failures can spoil supplies. Rural and conflict-affected areas face the greatest challenges due to weak logistics. Blood components have limited shelf lives: red blood cells last 42 days, platelets 5-7 days, and plasma up to one year if frozen.

These challenges demonstrate why the ability to print blood on demand is essential. Imagine a world where hospitals can print compatible, pathogen-free blood ready for transfusion. Currently, we cannot print blood itself, but we can produce the environment and components necessary for blood to function. Researchers have already developed plasma-based 3D printable materials, often enriched with platelets, that facilitate wound healing or support cell growth. Some laboratories can produce individual plasma proteins, such as albumin or clotting factors, using recombinant techniques, but combining them into a functional, transfusable plasma remains a future objective. Blood is considerably more complex than plasma alone. It is a living suspension of plasma, red and white blood cells, and platelets. What has been printed are red blood cell models at the microscale for studying oxygen transport and vascular networks, which could one day carry synthetic or donor-based plasma.

Plasma is chemically complex, but blood is both chemically and mechanically complex. From a printing or synthetic perspective, blood is harder to replicate because it requires reproducing the plasma composition, the cellular components, and their interactions, as well as their mechanical behaviour. Lab-grown red blood cells must carry oxygen, deform properly, and survive long enough to be effective. Printed blood cells degrade more quickly than natural ones, limiting practical application. Additionally, any printed blood or plasma must be sterile and immunologically compatible.

Printing blood and plasma could transform medicine. It could eliminate shortages, provide personalised transfusions, and deliver life-saving therapies anywhere. Perhaps we do not need to print every single drop of blood? Instead of recreating every cell and protein outside the body, we could print its precursors or boosters that the body itself multiplies into functional blood.
One promising approach uses hematopoietic stem cells (HSCs), the progenitors of red cells, white cells, and platelets. In the lab, these cells can be expanded into millions of functional blood cells. Imagine printing or injecting a small number of these stem cells and letting them grow into a full complement of blood components inside a bioreactor or in the patient’s own body.

Other strategies focus on oxygen carriers. Haemoglobin-based molecules and perfluorocarbon emulsions can temporarily transport oxygen without needing full red blood cells. Meanwhile, engineered platelet or plasma precursors could act as bio-boosters, stimulating the body to produce its own clotting factors and immune components. Furthermore, implantable micro-bioreactors are being researched. Tiny devices seeded with precursor cells could continuously produce blood components on demand, potentially reducing the need for donor blood entirely.

We may not need to print every drop of blood. By combining printing technology with the body’s natural biology, we can create a system where a small, engineered input multiplies into a complete, functional lifeblood.

Blood is life,
Yours Possibly

Further Reading

Ahlfeld, T., Cubo-Mateo, N., Cometta, S., Guduric, V., Vater, C., Bernhardt, A., Akkineni, A.R., Lode, A. and Gelinsky, M., 2020. A novel plasma-based bioink stimulates cell proliferation and differentiation in bioprinted, mineralized constructs. ACS applied materials & interfaces, 12(11), pp.12557-12572.
Del Amo, C., Perez-Valle, A., Perez-Garrastachu, M., Jauregui, I., Andollo, N., Arluzea, J., Guerrero, P., de la Caba, K. and Andia, I., 2021. Plasma-based bioinks for extrusion bioprinting of advanced dressings. Biomedicines, 9(8), p.1023.
Kim, E.J., Chen, C., Gologorsky, R., Santandreu, A., Torres, A., Wright, N., Goodin, M.S., Moyer, J., Chui, B.W., Blaha, C. and Brakeman, P., 2023. Feasibility of an implantable bioreactor for renal cell therapy using silicon nanopore membranes. Nature Communications, 14(1), p.4890.
Kim, J.H., Jung, E.A. and Kim, J.E., 2024. Perfluorocarbon-based artificial oxygen carriers for red blood cell substitutes: considerations and direction of technology. Journal of Pharmaceutical Investigation, 54(3), pp.267-282.
Maheshwari, D.T., Kumar, M.Y. and Indushekar, R., 2024. Mini review on Artificial Blood Substitutes: Future perspective of Perfluorocarbon based oxygen carriers. Medical Research Archives, 12(6).
Meaker, G.A. and Wilkinson, A.C., 2024. Ex vivo hematopoietic stem cell expansion technologies: recent progress, applications, and open questions. Experimental hematology, 130, p.104136.
Nalesso, F., Garzotto, F., Cattarin, L., Bettin, E., Cacciapuoti, M., Silvestre, C., Stefanelli, L.F., Furian, L. and Calò, L.A., 2024. The future for end-stage kidney disease treatment: Implantable bioartificial kidney challenge. Applied Sciences, 14(2), p.491.
Sobreiro‐Almeida, R., Santos, S.C., Decarli, M.C., Costa, M., Correia, T.R., Babilotte, J., Custódio, C.A., Moroni, L. and Mano, J.F., 2024. Leveraging Blood Components for 3D Printing Applications Through Programmable Ink Engineering Approaches. Advanced Science, 11(47), p.2406569.
Yokomizo, T. and Suda, T., 2024. Development of the hematopoietic system: expanding the concept of hematopoietic stem cell-independent hematopoiesis. Trends in Cell Biology, 34(2), pp.161-172.
Zhao, M., Liu, H. and Jahr, J.S., 2024. Perfluorocarbon-based oxygen carriers: What is new in 2024?. Journal of Anesthesia and Translational Medicine, 3(1), pp.10-13.
Zhao, M., Wang, J., Zhang, J., Huang, J., Luo, L., Yang, Y., Shen, K., Jiao, T., Jia, Y., Lian, W. and Li, J., 2022. Functionalizing multi-component bioink with platelet-rich plasma for customized in-situ bilayer bioprinting for wound healing. Materials Today Bio, 16, p.100334.