Mineralized cryogels to recapitulate the bone marrow microenvironment in acute myeloid leukemia

• Applicant: Valentina Magno, Ph.D.
• Subject Area: Biomaterials
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 557533144

The proposed project aims to develop and validate an innovative mineralized macroporous cryogel model for in vitro culture of acute myeloid leukemia (AML) cells that recreates the trabecular structure of the spongy bone and mimics the non-cellular microenvironment of the endosteal niche. Based on a highly modular poly(ethylene glycol) (PEG)-sulfated glycosaminoglycans (sGAG) network, the model will provide fine-tuned and sustained gradients of AML-relevant cytokines, offering significant improvements over existing approaches. Furthermore, thanks to a defined mineralization approach, the model will mimic the natural mineral size and composition of the endosteum, allowing the investigation of the role of calcium in regulating leukemic stem cells' fate and function. Finally, to enhance its physiological relevance, AML cells will be cultured within decellularized cryogels derived from AML-mesenchymal stromal cells (MSCs), closely mimicking the native bone marrow microenvironment and providing a foundation for patient-specific preclinical drug screenings. The key objectives can be summarized as follows: 1) Develop engineered endosteal niches using mineralized cryogels (mCRYOs) to study the role of bone-like minerals and sustained cytokine gradients (IL-6, SDF-1) in supporting AML cell self-renewal and survival. 2) Create a more realistic AML microenvironment using ECM-functionalized, decellularized cryogels (dmCRYOs) derived from MSCs of AML patients and healthy donors. Analyze the ECM's role in influencing AML cell behavior. 3) Validate the developed cryogels as drug screening platforms by assessing AML cell response to chemotherapy agents, also focusing on how IL-6 and SDF-1 influence treatment outcomes. 4) Investigate the role of bone minerals and calcium signaling in chemotherapy resistance, combining standard drugs with calcium signaling inhibitors to enhance treatment efficacy.

• DFG Programme: Research Grants
• Co-Investigator: Professorin Manja Wobus