An Automated and Controlled Three-Dimensional Bioprinting Process to Fabricate Niche-like Acute Myeloid Leukemia Disease Model
Acute myeloid leukemia (AML) is a hematological malignancy that remains a therapeutic challenge due to the high incidence of disease relapse. To better understand resistance mechanisms and identify novel therapies, robust preclinical models mimicking the bone marrow (BM) microenvironment are needed.This study aimed to achieve an automated fabrication process of a three-dimensional (3D) AML disease model that recapitulates the 3D spatial structure of the BM microenvironment and be used in drug screening.To build this model, we investigated a unique class of tetramer peptides with an innate ability to self-assemble into stable hydrogels. The selected peptide hydrogel formed a highly porous network of nanofibers with mechanical properties similar to the BM extracellular matrix (ECM). An automated robotic bioprinting process was established to fabricate a 3D niche-like model comprised of the BM's stromal and endothelial cellular fractions. This model supported the viability and growth of primary leukemic and stromal cells and recapitulated cell-cell and cell-ECM interactions. A unique feature of this model was the ability to induce a quiescence state as well as drug resistance in leukemic cells. In addition, it has promise for drug screening and the development of personalized medicine to test patient-specific therapeutics.