Fibroblasts alter the physical properties of dermal ECM-derived hydrogels to create a pro-angiogenic microenvironment

Meng Zhang; Fenghua Zhao; Xue Zhang; Linda A Brouwer; Janette K Burgess; Martin C Harmsen

doi:10.1016/j.mtbio.2023.100842

Fibroblasts alter the physical properties of dermal ECM-derived hydrogels to create a pro-angiogenic microenvironment

Mater Today Bio. 2023 Oct 24:23:100842. doi: 10.1016/j.mtbio.2023.100842. eCollection 2023 Dec.

Authors

Meng Zhang^{1

2}, Fenghua Zhao^{2

3}, Xue Zhang^{1

2}, Linda A Brouwer¹, Janette K Burgess^{1

2

4}, Martin C Harmsen^{1

2

4}

Affiliations

¹ University of Groningen, University Medical Centre Groningen, Department of Pathology and Medical Biology, Hanzeplein 1 (EA11), 9713, GZ Groningen, the Netherlands.
² University of Groningen, University Medical Centre Groningen, W.J. Kolff Institute for Biomedical Engineering and Materials Science-FB41, A. Deusinglaan 1, 9713, AV Groningen, the Netherlands.
³ University of Groningen, University Medical Centre Groningen, Department of Biomedical Engineering-FB40, A. Deusinglaan 1, 9713, AV Groningen, the Netherlands.
⁴ University of Groningen, University Medical Centre Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Hanzeplein 1 (EA11), 9713, AV Groningen, the Netherlands.

Abstract

This study aimed to investigate the impact of fibroblasts (MRC-5) on the extracellular matrix (ECM) microenvironment of endothelial cells (ECs) during the vascularization of skin-derived ECM hydrogel in vitro. Two types of ECs were studied: human dermal microvascular endothelial cells (HMEC) and human pulmonary microvascular endothelial cells (HPMEC). Results showed that the presence of MRC-5 fibroblasts increased the stiffness of the hydrogel and led to larger fiber diameters and increased porosity. Extensive collagen fiber remodeling occurred in the ECM hydrogel with MRC-5 fibroblasts. Additionally, higher levels of fibulin-1 and fibronectin were deposited in the hydrogel when co-cultured with MRC-5 fibroblasts. These findings suggest that MRC-5 fibroblasts play a role in modifying the ECM microenvironment, promoting vascularization through dynamic ECM remodeling.

Keywords: Biomechanics; Collagen; ECM hydrogel; Endothelial cells; Extracellular matrix; Fibronectin; Vascularization.