Bioprinting of high cell‐density constructs leads to controlled lumen formation with self‐assembly of endothelial cells. (17th July 2019)

• Record Type: Journal Article
• Authors: Tröndle, Kevin; Koch, Fritz; Finkenzeller, Günter; Stark, G. Björn; Zengerle, Roland; Koltay, Peter; Zimmermann, Stefan
• Is Part Of: Journal of tissue engineering and regenerative medicine. Volume 13:Number 10(2019)
• Page Start: 1883
• Page End: 1895
• Publication Date: 2019-07-17
• Subjects: drop on demand -- lumen formation -- self‐assembly -- suspension bioink; Tissue engineering -- Periodicals; Regeneration (Biology) -- Periodicals; 610.28
• DOI: 10.1002/term.2939
• Languages: English
• ISSNs: 1932-6254

Abstract

Abstract: Active nutrient supply and waste product removal are key requirements for the fabrication of long‐term viable and functional tissue constructs of considerable size. This work aims to contribute to the fabrication of artificial perfusable networks with a bioprinting process, based on drop‐on‐demand (DoD) printing of primary endothelial cell (EC) suspension bioink (25 × 10 6 ± 3 × 10 6 cells/ml). The process results in prescribed lumen between two hydrogel layers, allowing its integration in common layering based bioprinting processes. Low volume bioink droplets (appr. 10 nl) as building blocks were deposited between two fibrin or Collagen I layers to realize shapeable, cell‐rich aggregates. Unattainable with manual positioning, DoD printing allowed precise fabrication of various designs, such as spheroidal‐, line‐shaped, and Y‐branch cellular structures, with a mean lateral extension of 285 ± 81 μm. For basic characterization, the cell suspension building blocks were systematically compared with preformed spheroids of the same cell type, passage, and number. Post printing investigations of initially loose cell arrangements showed self‐assembly and formation of central lumen with a mean cross‐sectional area of Ølumen = 6, 400 μm 2 at Day 3, lined by a single layer of CD31 positive ECs, as evaluated by confocal microscopy. Originating from this main lumen smaller, undirected side branches (Øbranches = 740 μm 2 ) were formed by sprouting cells, inducing a first step towards a simplistic hierarchically organized network. These lumen could prospectively help for tissue construct perfusion in vitro or, potentially, as niche for angiogenesis of host vascularization in implants.