Electrospun PLA/PCL Composite Scaffolds as Platforms for Investigating Colorectal Cancer Cell Plasticity

Electrospun nanofibrous scaffolds are promising tools for in vitro cancer modeling due to their tunable architecture and biocompatibility. This study compares the effects of PLA, PCL, and their 1:1 blend (PLA/PCL) scaffolds on colorectal cancer (CRC) cell lines HT-29 and HCT116. Morphological and physicochemical analyses of the scaffolds confirmed uniform, bead-free fibers with slight alterations in crystallinity and hydrophobicity. Scaffold-specific biological responses included differences in cell morphology, viability, proliferation, metabolism, and gene expression related to EMT, stemness, ECM interaction, and adhesion. PLA/PCL scaffolds indicated enhanced cell adhesion and proliferation and retained metabolic activity over time. Gene expression profiling revealed significant upregulation of EMT (VIM, CDH2) and ECM (COL5A1) markers in both cell lines cultured on the PLA/PCL composite, with HT-29 showing elevated stemness (CD133) and adhesion (ICAM1), while HCT116 exhibited a hybrid EMT phenotype. Collectively, this work highlights the potential of PLA/PCL electrospun scaffolds to bridge conventional 2D cultures and complex 3D systems, thereby advancing in vitro colorectal cancer modeling and therapeutic testing for preclinical evaluations.