Exploring the Potential of PEG-Heparin Hydrogels To Support Long-term Ex Vivo Culture of Patient-derived Breast Explant Tissues.

Breast cancer is a complex, highly heterogenous, and dynamic disease and the leading cause of cancer-related death in women worldwide. Evaluation of the heterogeneity of breast cancer and its various subtypes is crucial to identify novel treatment strategies that can overcome the limitations of currently available options. Explant cultures of human mammary tissue have been known to provide important insights for the study of breast cancer structure and phenotype as they include the context of the surrounding microenvironment, allowing for the comprehensive exploration of patient heterogeneity. However, the major limitation of currently available techniques remains the short-term viability of the tissue owing to loss of the structural integrity. Here, we present an ex vivo culture model using star-shaped poly(ethylene glycol) and maleimide-functionalized heparin (PEG-HM) hydrogels to provide structural support to the explant cultures. The mechanical support allowed the culture of the human mammary tissue for up to 3 weeks and prevented disintegration of the cellular structures including the epithelium and surrounding stromal tissue. Further, we observed maintenance of epithelial phenotype and hormonal receptors for up to 2 weeks of culture which makes them relevant for testing therapeutic interventions. Through this study, we reiterate the importance of donor-to-donor variability and intra-patient tissue heterogeneity. This article is protected by copyright. All rights reserved.