Synthesis and characterization of oxidized alginate hydrogels as in vitro model for breast cancer

  • Chen Zhao

Student thesis: Phd


During the development of breast cancer, the stiffness of breast tissue can increase from 0.2 kPa (normal tissue) to 16 kPa (primary tumour tissue) due to the disrupted cellular environment. The altered microenvironment stimulates abnormal cellular activities and promotes progression of the disease. Three-dimensional (3D) in vitro models are often used to investigate how mechanics of the microenvironment impact on cellular behaviour. Several biomaterials have been reported to be used in 3D models; however, many of them are bioactive and capable to elicit a specific biological response or lack in controlling stiffness values. Alginate and oxidized alginate are biologically inert, biocompatible and able to control resultant stiffness; moreover, oxidized alginate is degradable both in vitro and in vivo. Alginate, oxidized alginate and gelatin were selected to formulate hydrogels with controlled stiffness in the range of 1-20 kPa to model normal and cancerous breast tissues, and mimic variations of mechanical properties during cancer development. The main objectives of this research were identified as: 1) manufacture and characterize oxidized alginates with known degrees of oxidation (Chapter 3); 2) formulate oxidized alginate-gelatin hydrogels with target compressive moduli in the range of 1-20 kPa; and good stability over time in cell culture conditions (Chapter 4), and 3) evaluate cytotoxicity of hydrogels to be further used in 3D in vitro models (Chapter 5). A two-step gelation method was proposed: two different types of oxidized alginate-gelatin (type 2 and type 3) hydrogels were prepared and mechanical properties characterized. Cytotoxicity of selected hydrogels was tested using a human breast cancer cell line (MDA-MB-231). In conclusion, with the increase of degree of oxidation, oxidized alginate shows lower molecular weight and higher aldehyde concentration (Chapter 3). Both type 2 and type 3 hydrogels possess tuneable mechanical properties in the range of interest and with required stability (up to 5 days) (Chapter 4), as well as good compatibility with breast cancer cells (Chapter 5). These hydrogels will enable to model stiffness variations of the breast tumour microenvironment in vitro, allowing a deeper understanding of cell-matrix interaction within the tumour microenvironment and the effects of stiffness to cell behaviour in a more physiologically relevant context.
Date of Award31 Dec 2022
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorKaye Williams (Supervisor), Ayse Latif (Supervisor) & Annalisa Tirella (Supervisor)


  • mechanical properties
  • oxidized alginate
  • hydrogels
  • in vitro model
  • breast cancer

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