Return to search

Fabrication of 3D Multicellular Acute Lymphoblastic Leukemia Disease Models Using Biofunctionalized Peptide-Based Scaffolds

Acute Lymphoblastic Leukemia (ALL) is one of the most common type of hematologic malignancy in children, characterized by an excessive proliferation of unfunctional immature lymphoblasts in the blood and the bone marrow, which leads to a range of severe blood-related complications. Given the remarkable increase in the prevalence of leukemia in the past 20 years, there has been a particular interest in the development of in vitro experimental models for cancer research. Ultra-short self-assembling peptides have shown to be a promising class of synthetic biomaterials due to their biocompatibility, tunable mechanical properties, and the possibility of controlling the scaffold composition. The objective of this study was to create a bioactive but well-defined synthetic 3D model of the bone marrow (BM) microenvironment for the simulation of ALL using biofunctionalized ultrashort self-assembling peptide scaffolds. Different bioactive motifs derived from integral extracellular matrix (ECM) constituents that are known to enhance cell-matrix adhesion, including RGDS from fibronectin, YIGSR from laminin, and GFOGER from collagen, were incorporated into the parent peptide IIZK. These peptides demonstrated to be capable of generating stable hydrogel structures composed of fibrous porous networks, each with unique nanofiber morphology and mechanical properties. All the peptide scaffolds that were investigated in this study exhibited optimal characteristics concerning the cytocompatibility of multiple BM niche cells, including human bone marrow mesenchymal stem cells (MSCs), human umbilical vein endothelial cells (HUVECs), and patient derived ALL cells. The suitability of the scaffolds as drug screening platforms was evaluated, demonstrating their potential as versatile tools for the assessment of drug efficacy.

Identiferoai:union.ndltd.org:kaust.edu.sa/oai:repository.kaust.edu.sa:10754/693407
Date07 1900
CreatorsBaldelamar Juarez, Cynthia Olivia
ContributorsHauser, Charlotte, Biological and Environmental Science and Engineering (BESE) Division, Mahfouz, Magdy M., Habuchi, Satoshi
Source SetsKing Abdullah University of Science and Technology
LanguageEnglish
Detected LanguageEnglish
TypeThesis
Rights2024-08-02, At the time of archiving, the student author of this thesis opted to temporarily restrict access to it. The full text of this thesis will become available to the public after the expiration of the embargo on 2024-08-02.
RelationN/A

Page generated in 0.0026 seconds