eCM (Eur Cell Mater / e Cells & Materials) Not-for-profit Open Access
Created by Scientists, for Scientists
 ISSN:1473-2262         NLM:100973416 (link)         DOI:10.22203/eCM

2018   Volume No 35 – pages 335-349

Title: Engineering of a complex bone tissue model with endothelialised channels and capillary-like networks

Authors: BJ Klotz, KS Lim, YX Chang, BG Soliman, I Pennings, FPW Melchels, TBF Woodfield, AJWP Rosenberg, J Malda, D Gawlitta

Address: UMC Utrecht, Heidelberglaan 100, PO Box 85500, 3508GA Utrecht, the Netherlands

E-mail: D.Gawlitta at

Abstract: In engineering of tissue analogues, upscaling to clinically-relevant sized constructs remains a significant challenge. The successful integration of a vascular network throughout the engineered tissue is anticipated to overcome the lack of nutrient and oxygen supply to residing cells. This work aimed at developing a multiscale bone-tissue-specific vascularisation strategy.
Engineering pre-vascularised bone leads to biological and fabrication dilemmas. To fabricate channels endowed with an endothelium and suitable for osteogenesis, rather stiff materials are preferable, while capillarisation requires soft matrices. To overcome this challenge, gelatine-methacryloyl hydrogels were tailored by changing the degree of functionalisation to allow for cell spreading within the hydrogel, while still enabling endothelialisation on the hydrogel surface.
An additional challenge was the combination of the multiple required cell-types within one biomaterial, sharing the same culture medium. Consequently, a new medium composition was investigated that simultaneously allowed for endothelialisation, capillarisation and osteogenesis. Integrated multipotent mesenchymal stromal cells, which give rise to pericyte-like and osteogenic cells, and endothelial-colony-forming cells (ECFCs) which form capillaries and endothelium, were used.
Based on the aforementioned optimisation, a construct of 8 × 8 × 3 mm, with a central channel of 600 µm in diameter, was engineered. In this construct, ECFCs covered the channel with endothelium and osteogenic cells resided in the hydrogel, adjacent to self-assembled capillary-like networks. This study showed the promise of engineering complex tissue constructs by means of human primary cells, paving the way for scaling-up and finally overcoming the challenge of engineering vascularised tissues.

Key Words: Co-culture, endothelial colony-forming cells, mesenchymal stromal cells, capillaries, endothelium, culture medium, osteogenesis, vasculogenesis, gelatine-methacryloyl, hydrogel.

Publication date: June 6th 2018

Article download: Pages 335-349

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