Exploring the Potential of PEG‐Heparin Hydrogels to Support Long‐Term Ex Vivo Culture of Patient‐Derived Breast Explant Tissues

• Published in: Advanced healthcare materials Vol. 12; no. 14; pp. e2202202 - n/a
• Main Authors: Koch, Maria K., Ravichandran, Akhilandeshwari, Murekatete, Berline, Clegg, Julien, Joseph, Mary Teresa, Hampson, Madison, Jenkinson, Mitchell, Bauer, Hannah S., Snell, Cameron, Liu, Cheng, Gough, Madeline, Thompson, Erik W., Werner, Carsten, Hutmacher, Dietmar W., Haupt, Larisa M., Bray, Laura J.
• Format: Journal Article
• Language: English
• Published: Germany 01.06.2023
• Subjects: Biocompatible Materials; breast cancer; Breast Neoplasms - drug therapy; ex vivo cultures; Female; Heparin - pharmacology; Humans; hydrogels; Hydrogels - chemistry; Hydrogels - pharmacology; patient‐derived explants; Polyethylene Glycols - chemistry; Polyethylene Glycols - pharmacology; Tumor Microenvironment; ex vivo cultures; breast cancer; hydrogels; patient-derived explants
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.202202202

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 structural integrity. Here, 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 is presented. The mechanical support allows the culture of the human mammary tissue for up to 3 weeks and prevent disintegration of the cellular structures including the epithelium and surrounding stromal tissue. Further, maintenance of epithelial phenotype and hormonal receptors is observed for up to 2 weeks of culture which makes them relevant for testing therapeutic interventions. Through this study, the importance of donor‐to‐donor variability and intra‐patient tissue heterogeneity is reiterated. Patient‐derived normal breast and breast cancer explant tissues are embedded within poly(ethylene glycol)‐heparin‐maleimide (PEG‐HM) hydrogels and cultured ex vivo for a period of 3 weeks. Evaluating tissue integrity, functionality, and proliferation of embedded versus non‐embedded explant tissues allows for the study and development of alternative methods for long‐term cultures of patient‐derived breast tissues.