Welcome! We created this “who is who” interview series to help our community connect better and learn about SilkFusion, its partners and its experts.
|Organization||University of Pavia|
The demand for human platelets for medical research and clinical applications is massive and growing. Why?
Platelets are necessary for blood to clot and stop bleeding. They are generated from giant cells called megakaryocytes that reside in the blood marrow of our bones. When bone marrow is unable to produce enough platelets, the body bruises and bleeds more easily, for example blood won’t clot when you get a cut and the chance of internal bleeding during surgery or after a big trauma increase.
Millions of platelet transfusions are needed each year to treat people suffering from hematological diseases, viral infections or chemotherapy. Today the main source of platelets is from healthy donors and immunological matches are a big issue. Platelet shortage is common when donation rates are down, mainly during summer, or during public health emergencies, such as pandemics – think of the effect the lockdown had on donations this year!
Platelets cannot be stored for more than a few days and only at room temperature. Given their short shelf lifespan, platelets must be screened for bacteria and viruses quickly and delivered immediately to individuals who need them. This translates into a recurring shortage worldwide.
SilkFusion is focused on solving this demand with a novel 3D solution for large-scale ex-vivo platelet production, transfusion and drug research. How does SilkFusion work?
SilkFusion is engineering a groundbreaking platform which combines the use of silk, 3D nanotechnologies and 3D printing to recreate the environment of the human bone marrow where platelets are produced. We believe that we can program lab grown megakaryocytes to believe they are inside a human body and have them produce platelets on-demand, in greater quantities, with better control of quality, safety and compatibility with recipients than with donor platelets.
SilkFusion is the first industrialisable 3D silk-fibroin technology for ex-vivo large-scale production of blood platelets. Why will SilkFusion revolutionize personalized medicine?
Some individuals with rare blood diseases need precisely matched transfusions that come from specific donors. You can imagine, as it gets scaled up and industrialized, SilkFusion could have systems generating personalized platelets for patients on demand or systems generating universally compatible platelets.
Our 3D technology is especially exciting for researchers and clinicians by allowing them to conduct pharmacological studies on human cells. Testing efficacy of new drugs costs millions of dollars for a single drug compound and often animal models are poor predictors of outcomes in humans. Bypassing animals, the SilkFusion technology provides a sensitive system for ex-vivo screening of new therapeutic options directly on patients’ megakaryocytes, thus leading to the choice of the best therapeutic course for patients and ultimately to improvements in clinical care.
SilkFusion solution combines three technologies developed by the consortium partners. Could you tell us about them?
The SilkFusion consortium is the result of the synergic collaboration between European academic research teams and companies. The University of Pavia, in Italy, provides the know-how in using silk as biomaterial to mimic the bone marrow and together with CELLINK, a world leading bioink company with headquarters in Sweden, is looking to create the first 3D printable human bone marrow. The silk-bone marrow will house cells developed by the University of Cambridge in UK and the INSERM in France. Both have long-term experience in generating human cells able to produce unlimited quantities of megakaryocytes, whose quality and safety are strictly controlled by the Italian Biobank ISENET. We believe that collaborative research leveraging the strengths of multiple investigators is critical to make our outstanding technology to come to large scale fruition. Also, the participation of an extremely talented and motivated group of graduate students and postdoctoral researchers makes a big contribution to this challenge.
SilkFusion´s hypothesis is that platelet production ex-vivo can be precision tailored and optimized by providing megakaryocytes embedded within the correct physical and biochemical environment. Why is this so interesting?
Human megakaryocytes like to lay on soft and smooth surfaces when they produce platelets. You need to put together the right signals, morphology and features to get megakaryocytes to behave properly ex-vivo. Silk protein possesses a unique molecular structure that allows it to be modeled in a wide variety of forms and stiffnesses. Silk is biocompatible and has the ability to incorporate and stabilize molecules that support the formation the platelets. SilkFusion can model and ‘functionalize’ the silk by adding the necessary molecules directly within its fibers to drive maximum platelet production.
How does SilkFusion to prove this hypothesis?
SilkFusion can model silk to create different 3D environments having a resilient structure and variable stiffness. Megakaryocytes hook up to the silk fibers that they think are their native bone marrow environment, send out long projectiles through the 3D space and shed platelets into a flowing artificial blood stream. To prove our ability to produce platelets, we are growing human megakaryocytes into the SilkFusion system and testing how they behave in terms of numbers of platelets collected.
Why is silk so important?
The silk of bombyx mori silkworms is totally compatible with human cells and easily customized to a wide variety of organic structures. The silk itself is interesting for our 3D printing technology because it gives us just the right chemistry and structure to avoid overstimulating megakaryocytes and platelets. You can’t just use any material because they prevent megakaryocytes from producing platelets or cause premature exhaustion of newly formed platelets. With SilkFusion you can 3D print megakaryocytes into a liquid silk-based medium which then solidifies and keeps the 3D structure that supports the physiologic process of natural platelet production.
What is your role in this project?
I am the coordinator of the project. For 15 years my research has focused on understanding the mechanisms of platelet production in bone marrow and on the clinical aspects of human diseases related to platelets and clotting processes. After starting a collaboration with the Department of Biomedical Engineering of Tufts University, in Boston (USA), I had the intuition that silk could be potentially great to recreate the bone marrow ex-vivo. The synergy between my expertise in blood cells, hematological diseases and in silk processing has led to the development of early models of silk-bone marrow able to produce human platelets that laid the groundwork for SilkFusion to create systems which not only yield more platelets but are also more scalable and programmable.