Revolutionary silk-based bioink for 3D printing of ex vivo bone marrow models to advance drug development and personalized medicine

Informations projet

SILKink

N° de convention de subvention: 101113073

DOI

10.3030/101113073

Projet clôturé

Date de signature de la CE 26 Avril 2023

Date de début 1 Juin 2023

Date de fin 31 Mai 2026

Financé au titre de

• The European Innovation Council (EIC)

Coût total

€ 2 494 687,50

Contribution de l’UE

€ 2 494 687,50

Coordonné par

UNIVERSITA DEGLI STUDI DI PAVIA
Italy

Periodic Reporting for period 1 - SILKink (Revolutionary silk-based bioink for 3D printing of ex vivo bone marrow models to advance drug development and personalized medicine)

Période du rapport: 2023-06-01 au 2024-05-31

Résumé du contexte et des objectifs généraux du projet

Cancer and Hematological Challenges:

Cancer is becoming more prevalent worldwide, especially among the elderly, with over 19 million new cases and 10 million deaths annually. Hematological cancers account for about 7% of these deaths. In Europe, the economic burden of cancer exceeds €100 billion each year. Patients suffering from therapy-induced bone marrow failure incur higher hospitalization costs and face increased mortality. To better understand the mechanisms behind bone marrow failure during cancer treatment, there is a need for advanced in vitro models that accurately replicate the human bone marrow microenvironment. Such models are essential for enhancing drug development in the pharmaceutical industry and advancing personalized medicine in clinical settings.

Challenges in Culturing HSPCs:

Culturing human hematopoietic stem and progenitor cells (HSPCs), which are vital for producing red blood cells and platelets, is challenging. These cells are delicate and require soft, smooth surfaces to differentiate properly. Current methods fail to accurately replicate the bone marrow environment, limiting the development of new drugs and personalized treatments.

SILKink Project Solution:

The SILKink project, funded by the EIC, is developing a new bio-ink made from silk for 3D bioprinting. This innovative material will create accurate models of bone marrow tissue, simulating HSPC functions outside the body.

Key Benefits:

Better Research: Allows consistent culture of human HSPCs.
Versatile Use: Silk's compatibility with 3D printing offers a wide range of culture conditions.
High Efficiency: Supports high-throughput drug discovery.
Human-Specific Testing: Suitable for testing drugs that can't be evaluated in animals.
Low Cell Requirement: Enables screening of new treatments using minimal cells from patients.

This project aims to improve patient care by offering a reliable platform for studying HSPCs and testing new therapies.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

The primary objective of the first year of the project has been to optimize the silk-based bioink for 3D bioprinting with the right balance of viscosity and stiffness to ensure smooth printing, precise layer formation, and gel-like consistency. The bioink has been developed to support HSPC viability, proliferation, and differentiation through appropriate biochemical cues.
Effective printing protocols have been set to ensure high repeatability, standardization, fidelity of constructs, and reliable cell culture. We demonstrated that controlled extrusion of SILKink ensures homogeneous cell embedding, spatial distribution, and efficient nutrient diffusion, vital for proper cell viability, differentiation, and function. Particularly, SILKink supports the controlled differentiation of human HSPCs into platelets. Optical transparency allows high-resolution imaging of platelet generation, and enzymatic sensors enable quantitative analysis of glycolytic metabolism during differentiation, indicated by measurable color changes. Bioprinting samples from patients affected by Inherited Platelet Disorders provided a proof-of-concept of the applicability of the soft bone marrow mode as a tool for classifying thrombocytopenia and automating the assessment of responses to treatments at an individual scale.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

We are currently focused on upscaling the production of SILKink, ensuring a consistent supply for various research and clinical applications. Additionally, we are working on enhancing the long-term stability of the product. This stability is crucial for maintaining the bioink’s efficacy and usability over extended periods. To facilitate this, we are developing silk-compatible packaging that preserves the bioink’s properties during storage. Furthermore, we are optimizing shipment conditions to ensure that SILKink retains its quality and functionality from production to end-use, providing a reliable and effective tool for drug development and personalized medicine, with a particular focus on the treatment of thrombocytopenia.
The writing of the business plan and preparation of the investor slide deck follow the timeline indicated in the grant agreement. The completion of the business case for the clinical market is ongoing. Additionally, we are developing a comprehensive regulatory strategy to facilitate the commercialization of SILKink for personalized diagnostics and personalized therapeutics applications. This strategy includes assessing the investment required to set up GMP manufacturing.

SILKink workflow