Multi-parametric hydrogels support 3D in vitro bioengineered microenvironment models of tumour angiogenesis

Laura J Bray; Marcus Binner; Anja Holzheu; Jens Friedrichs; Uwe Freudenberg; Dietmar W Hutmacher; Carsten Werner

doi:10.1016/j.biomaterials.2015.02.124

Multi-parametric hydrogels support 3D in vitro bioengineered microenvironment models of tumour angiogenesis

Biomaterials. 2015:53:609-20. doi: 10.1016/j.biomaterials.2015.02.124. Epub 2015 Mar 24.

Authors

Laura J Bray¹, Marcus Binner², Anja Holzheu², Jens Friedrichs², Uwe Freudenberg², Dietmar W Hutmacher³, Carsten Werner²

Affiliations

¹ Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Center for Regenerative Therapies Dresden, Hohe Straße 6, 01069 Dresden, Saxony, Germany; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, 2 George Street, Brisbane, Queensland 4000, Australia; Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, Queensland 4059, Australia. Electronic address: bray@ipfdd.de.
² Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Center for Regenerative Therapies Dresden, Hohe Straße 6, 01069 Dresden, Saxony, Germany.
³ Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, Queensland 4059, Australia.

PMID: 25890757
DOI: 10.1016/j.biomaterials.2015.02.124

Abstract

Tumour microenvironment greatly influences the development and metastasis of cancer progression. The development of three dimensional (3D) culture models which mimic that displayed in vivo can improve cancer biology studies and accelerate novel anticancer drug screening. Inspired by a systems biology approach, we have formed 3D in vitro bioengineered tumour angiogenesis microenvironments within a glycosaminoglycan-based hydrogel culture system. This microenvironment model can routinely recreate breast and prostate tumour vascularisation. The multiple cell types cultured within this model were less sensitive to chemotherapy when compared with two dimensional (2D) cultures, and displayed comparative tumour regression to that displayed in vivo. These features highlight the use of our in vitro culture model as a complementary testing platform in conjunction with animal models, addressing key reduction and replacement goals of the future. We anticipate that this biomimetic model will provide a platform for the in-depth analysis of cancer development and the discovery of novel therapeutic targets.

Keywords: Angiogenesis; Carcinogenesis; Cell culture; ECM; Heparin; Hydrogel.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / therapeutic use
Cell Line, Tumor
Humans
Hydrogels*
Models, Biological
Neoplasms / blood supply*
Neoplasms / drug therapy
Neovascularization, Pathologic*
Tumor Microenvironment*

Substances

Antineoplastic Agents
Hydrogels