Can electrospun scaffolds be used for the support of breast tissue culture in a Breast-on-a-Chip model?

Abstract

Breast cancer remains a significant global health challenge, that requires the improvement and development of novel techniques to enhance our understanding of disease progression and to develop effective therapeutic strategies. This research outlines recent advancements in the development of pre-clinical research models to study breast tumorigenesis, with particular attention to the incorporation of synthetic polymeric electrospun scaffolds within a pioneering Breast-on-a-Chip (BoC) device. Seeking alternative membranes to the vastly used animal-derived extra cellular matrix, MatrigelTM; synthetic scaffolds were produced using Polyvinyl Alcohol (PVA), Polyurethane (PU), Gelatin (Ge), and Poly-(Ɛ-caprolactone) (PCL) through the versatile electrospinning process. Extensive characterisation studies were undertaken using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (ATR-FTIR), and degradation tests to understand the scaffolds' biocompatibility with MCF-12A (epithelial), HMF (fibroblasts) and HMMEC (endothelial) cell cultures. Results demonstrated the HMF morphological organisation is mirrored by PU and PVA scaffolds, as demonstrated by microscopy examination. These cell types were selected for their ability to recreate a simplistic model of healthy breast tissue. MCF-12A seeding onto PU scaffolds demonstrated favourable acini formation, critical for tissue and disease modelling. Similarly, endothelial cells displayed enhanced survival rates on PVA membranes, resembling MatrigelTM controls. The novel integration of synthetic polymeric electrospun scaffolds into a BoC system emerges as a breakthrough. Leveraging PU and PVA-derived scaffold, this three-dimensional (3D) microenvironment brings it a step closer to emulating in vivo conditions, surpassing the limitations of traditional 2D cultures and static 3D models. Breast-derived cell lines demonstrated diverse behaviours, underlining the necessity of 3D microenvironments in capturing the complexity of biological interactions. This study establishes the viability of synthetic electrospun scaffolds in breast cancer research, highlighting their potential within BoC systems. The integration of these scaffolds into an innovative platform holds promise for transforming in vitro modelling by providing a physiologically relevant tool for studying breast cancer progression and therapeutic responses. These findings contribute to ongoing efforts to refine breast cancer research methodologies.