High-throughput non-homogenous 3D polycaprolactone scaffold for cancer cell and cancer-associated fibroblast mini-tumors to evaluate drug treatment response

作者：Atena Malakpour‐Permlid, Manuel Marcos Rodriguez, Gavrielle R. Untracht, Peter E. Andersen, Stina Oredsson, Anja Boisen, Kinga Zór · 发表于：Toxicology Reports · 年份：2024 · DOI：10.1016/j.toxrep.2024.101863 · 被引用次数：5 · 研究领域：Bone Tissue Engineering Materials、Graphene and Nanomaterials Applications、3D Printing in Biomedical Research

High-throughput screening (HTS) three-dimensional (3D) tumor models are a promising approach for cancer drug discovery, as they more accurately replicate in vivo cell behavior than two-dimensional (2D) models. However, assessing and comparing current 3D models for drug efficacy remains essential, given the significant influence of cellular conditions on treatment response. To develop in vivo mimicking 3D models, we evaluated two HTS 3D models established in 96-well plates with 3D polycaprolactone (PCL) scaffolds fabricated using two distinct methods, resulting in scaffolds with either homogenous or non-homogenous fiber networks. These models, based on human HeLa cervical cancer cells and cancer-associated fibroblasts (CAFs) cultured as mono- or co-cultures within the 3D scaffolds, revealed that anticancer drug paclitaxel (PTX) exhibited consistently higher inhibitory concentration 50 (IC 50 ) in 3D (≥ 1000 nM) compared to 2D (≥ 100 nM), indicating reduced toxicity on cells cultured in 3D. Interestingly, the toxicity of PTX was significantly lower on mini-tumors in non-homogenous 3D (IC 50 : 600 or 1000 nM) than in homogenous 3D cultures (IC 50 exceeding 1000 nM). Microscopic studies revealed that the non-homogenous scaffolds closely resemble the tumor collagen network than their homogeneous counterpart. Both 3D scaffolds offer optimal pore size, facilitating efficient cell infiltration into the depth of 58.1 ± 1.2 µm (homogenous) and 86.4 ± 9.8 µm (non-homogenous) within 3D c...