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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Maria K Koch - , Queensland University of Technology (Author)
  • Akhilandeshwari Ravichandran - , Queensland University of Technology (Author)
  • Berline Murekatete - , Queensland University of Technology (Author)
  • Julien Clegg - , Queensland University of Technology, Translational Research Institute Australia (Author)
  • Mary Teresa Joseph - , Queensland University of Technology (Author)
  • Madison Hampson - , Queensland University of Technology (Author)
  • Mitchell Jenkinson - , Queensland University of Technology (Author)
  • Hannah S Bauer - , Queensland University of Technology (Author)
  • Cameron Snell - , Mater Group Hospitals (Author)
  • Cheng Liu - , University of Queensland (Author)
  • Madeline Gough - , University of Queensland (Author)
  • Erik W Thompson - , Queensland University of Technology, Translational Research Institute Australia (Author)
  • Carsten Werner - , Leibniz Institute of Polymer Research Dresden (Author)
  • Dietmar W Hutmacher - , Max Planck Queensland Center (MPQC) (Author)
  • Larisa M Haupt - , Queensland University of Technology (Author)
  • Laura J Bray - , Max Planck Queensland Center (MPQC) (Author)

Abstract

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.

Details

Original languageEnglish
Article numbere2202202
JournalAdvanced healthcare materials
Volume12
Issue number14
Publication statusPublished - Jun 2023
Peer-reviewedYes
Externally publishedYes

External IDs

PubMedCentral PMC11469079
Scopus 85145734010
ORCID /0000-0003-0189-3448/work/173985679

Keywords

Sustainable Development Goals

Keywords

  • Biocompatible Materials, Breast Neoplasms/drug therapy, Female, Heparin/pharmacology, Humans, Hydrogels/pharmacology, Polyethylene Glycols/pharmacology, Tumor Microenvironment