Gelatin-containing porous polycaprolactone PolyHIPEs as substrates for 3D breast cancer cell culture and vascular infiltration

Caitlin E Jackson; Iona Doyle; Hamood Khan; Samuel F Williams; Betül Aldemir Dikici; Edgar Barajas Ledesma; Helen E Bryant; William R English; Nicola H Green; Frederik Claeyssens

doi:10.3389/fbioe.2023.1321197

Gelatin-containing porous polycaprolactone PolyHIPEs as substrates for 3D breast cancer cell culture and vascular infiltration

Front Bioeng Biotechnol. 2024 Jan 8:11:1321197. doi: 10.3389/fbioe.2023.1321197. eCollection 2023.

Authors

Caitlin E Jackson^{1

2}, Iona Doyle¹, Hamood Khan¹, Samuel F Williams³, Betül Aldemir Dikici⁴, Edgar Barajas Ledesma⁵, Helen E Bryant⁶, William R English⁷, Nicola H Green^{1

2}, Frederik Claeyssens^{1

2}

Affiliations

¹ The Kroto Research Institute, Materials Science and Engineering, University of Sheffield, Sheffield, United Kingdom.
² Insigneo Institute for in Silico Medicine, The Pam Liversidge Building, University of Sheffield, Sheffield, United Kingdom.
³ Department of Infection, Immunity and Cardiovascular Disease, Royal Hallamshire Hospital, The University of Sheffield, Sheffield, United Kingdom.
⁴ Department of Bioengineering, Izmir Institute of Technology, Urla, Türkiye.
⁵ Department of Chemistry, The University of Sheffield, Sheffield, United Kingdom.
⁶ School of Medicine and Population Health, University of Sheffield, Sheffield, United Kingdom.
⁷ Norwich Medical School, University of East Anglia, Norwich, United Kingdom.

Abstract

Tumour survival and growth are reliant on angiogenesis, the formation of new blood vessels, to facilitate nutrient and waste exchange and, importantly, provide a route for metastasis from a primary to a secondary site. Whilst current models can ensure the transport and exchange of nutrients and waste via diffusion over distances greater than 200 μm, many lack sufficient vasculature capable of recapitulating the tumour microenvironment and, thus, metastasis. In this study, we utilise gelatin-containing polymerised high internal phase emulsion (polyHIPE) templated polycaprolactone-methacrylate (PCL-M) scaffolds to fabricate a composite material to support the 3D culture of MDA-MB-231 breast cancer cells and vascular ingrowth. Firstly, we investigated the effect of gelatin within the scaffolds on the mechanical and chemical properties using compression testing and FTIR spectroscopy, respectively. Initial in vitro assessment of cell metabolic activity and vascular endothelial growth factor expression demonstrated that gelatin-containing PCL-M polyHIPEs are capable of supporting 3D breast cancer cell growth. We then utilised the chick chorioallantoic membrane (CAM) assay to assess the angiogenic potential of cell-seeded gelatin-containing PCL-M polyHIPEs, and vascular ingrowth within cell-seeded, surfactant and gelatin-containing scaffolds was investigated via histological staining. Overall, our study proposes a promising composite material to fabricate a substrate to support the 3D culture of cancer cells and vascular ingrowth.

Keywords: CAM assay; PCL (polycaprolactone); angiogenesis; gelatin; polyHIPE; vascularisation.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by EPSRC, grant number: EP/S022201/1 and EP/R513313/1, the Royal Society, grant number: SRF\R1\221053, The Department of Scientific Research Projects of Izmir Institute of Technology (IZTECH-BAP, 2021-IYTE-1-0110 and 2022-IYTE-2-0025), Health Institutes of Turkey (TUSEB-2022B02-22517) and IzTech Integrated Research Centers (IzTech IRC), the Center for Materials Research.