3D Disease Modelling of Hard and Soft Cancer Using PHA-Based Scaffolds

Area of Science:

• Biomaterials Science
• Cancer Biology
• Tissue Engineering

Background:

• Tumor cells alter shape and lose polarity in 3D cultures, mirroring in vivo tumor progression.
• Studying cancer cells in 3D environments that mimic in vivo conditions is crucial for accurate research.
• Biodegradable polyesters, polyhydroxyalkanoates (PHAs), offer a promising material for creating such 3D models.

Purpose of the Study:

• To establish 3D cancer tumor models using a blend of P(3HO-co-3HD) and P(3HB) polyesters.
• To investigate the cellular behavior and Epithelial Mesenchymal Transition (EMT) marker gene expression in these 3D models.
• To assess the suitability of these PHA scaffolds for mimicking in vivo tumor microenvironments.

Main Methods:

• Fabrication of 3D scaffolds from a blend of P(3HO-co-3HD) and P(3HB) with controlled pore sizes (30-300 µm).
• Culture of breast cancer cell lines (MCF7, MDA-MB-231) and colon cancer cell line (HCT116) within the 3D PHA scaffolds.
• Analysis of cell morphology, growth patterns, and expression levels of EMT marker genes (Wnt-11, Snail, Vim, E-Cadherin).

Main Results:

• The 3D PHA scaffolds facilitated nutrient diffusion and even cell distribution, supporting cell growth within pores.
• Distinct growth patterns were observed: MDA-MB-231 cells formed clusters, MCF7 cells formed dense layers, and HCT116 cells formed large colonies.
• MDA-MB-231 cells showed increased expression of Wnt-11 and mesenchymal markers (Snail, Vim), while MCF7 cells showed increased E-Cadherin expression, consistent with in vivo tumor samples.

Conclusions:

• The developed 3D PHA scaffolds effectively mimic key aspects of the in vivo tumor microenvironment.
• These models accurately represent Epithelial Mesenchymal Transition (EMT) marker expression in cancer cells.
• Future applications include more accurate studies of hypoxic tumors, gene expression, signaling, angiogenesis, and drug responses.