Biotetris: development of bone organoids using bioinspired cell-instructive microbiomaterials as matrix-mimicking building blocks for bottom-up bone regeneration therapies
Description: There is a growing demand in our aging population for bone transplant alternatives to effectively treat critical-sized skeletal defects caused by trauma, cancer removal and diseases. Tissue regeneration (TR) strives to provide such effective treatments. Nevertheless, it remains highly challenging to recapitulate the complex biology and hierarchical, multiscale architecture of bone. Bottom-up TR relies on self- or directed assembly of tissue building blocks into larger structures and has proven a successful strategy to create modular microtissues and organoids with biological complexity and hierarchy similar to those of native tissues and organs. However, similar bottom-up approaches for generating bone microtissues and organoids have been limited. The most advanced examples of bone organoids have been created by using only cells as building blocks, stimulated with osteogenic growth factors (GFs). Unfortunately, these efforts do not consider the extracellular matrix (ECM), which is a determinant for the properties and function of bone tissue. In Biotetris, I aim to develop bona-fide bone organoids by using human induced pluripotent stem cells (hiPSCs) as biological building blocks and engineered microbiomaterials as ECM-mimicking building blocks that provide mechanical support and guide osteogenic differentiation. Inspired by the ECM of native bone, the microbiomaterials will be based on mineralized natural and synthetic polymers. I will tune the microbiomaterials both at the submicron-scale (by adding biomimetic surface topographies or by chemical biofunctionalization) and at the micron-scale (by tailoring the particle size, outer shape and isotropy level) in order to gain further control over hiPSC-microbiomaterial interactions, and, consequently, cell fate. By three-dimensional (3D) culturing of the cells onto these microbiomaterials to direct cell assembly and osteogenic differentiations, spheroidal bone organoids will be generated. Finally, the organoids will be directed to assemble into larger structures using 3D templates inspired by the size and shape of critical-sized bone defects, to form meso-scale bone tissues.
Funding type: grant
Funder scheme: Stimuleringssubsidies Stimuleringssubsidies voor vrouwen in Bèta en Techniek 2020 Vrouwen in Bèta en Techniek - VBT 2020
Start date: 2021-01-01
End date: 2022-06-30
Investigator: Zeinab Niloofar Tahmasebi Birgani
Institution: Maastricht University
Funded outputs count: 11
Funder award ID: 18748
OpenAlex ID: G403007422