Advanced gelatin-based vascularization bioinks for extrusion-based bioprinting of vascularized bone equivalents

Scientific Reports, vol. 10, pp. 5330

Abstract

Bone tissue is highly vascularized. The crosstalk of vascular and osteogenic cells is not only responsible for the formation of the strongly divergent tissue types but also for their physiological maintenance and repair. Extrusion-based bioprinting presents a promising fabrication method for bone replacement. It allows for the production of large-volume constructs, which can be tailored to individual tissue defect geometries. In this study, we used the all-gelatin-based toolbox of methacryl-modified gelatin (GM), non-modified gelatin (G) and acetylated GM (GMA) to tailor both the properties of the bioink towards improved printability, and the properties of the crosslinked hydrogel towards enhanced support of vascular network formation by simple blending. The vasculogenic behavior of human dermal microvascular endothelial cells (HDMECs) and human adipose-derived stem cells (ASCs) was evaluated in the different hydrogel formulations for 14 days. Co-culture constructs including a vascular component and an osteogenic component (i.e. a bone bioink based on GM, hydroxyapatite and ASCs) were fabricated via extrusion-based bioprinting. Bioprinted co-culture constructs exhibited functional tissue-specific cells whose interplay positively affected the formation and maintenance of vascular-like structures. The setup further enabled the deposition of bone matrix associated proteins like collagen type I, fibronectin and alkaline phosphatase within the 30-day culture.

Authors 5

1. A. Leucht

   University of Stuttgart · Fraunhofer Institute for Interfacial Engineering and Biotechnology

   Affiliation as printed

   Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart, Germany

   Institute of Interfacial Process Engineering and Plasmatechnology IGVP, University of Stuttgart, Stuttgart, Germany

2. Ann‐Cathrin Volz

   Reutlingen University

   Affiliation as printed

   Reutlingen Research Institute, Reutlingen University, Reutlingen, Germany

3. Julia Rogal Aachen

   Fraunhofer Institute for Interfacial Engineering and Biotechnology · RWTH Aachen University

   Affiliation as printed

   Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart, Germany

   RWTH Aachen University, Aachen, Germany

4. Kirsten Borchers

   University of Stuttgart · Fraunhofer Institute for Interfacial Engineering and Biotechnology

   Affiliation as printed

   Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart, Germany

   Institute of Interfacial Process Engineering and Plasmatechnology IGVP, University of Stuttgart, Stuttgart, Germany

5. Petra J. Kluger corresponding

   Fraunhofer Institute for Interfacial Engineering and Biotechnology · Reutlingen University

   Affiliation as printed

   Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart, Germany. petra.kluger@reutlingen-university.de

   Reutlingen Research Institute, Reutlingen University, Reutlingen, Germany. petra.kluger@reutlingen-university.de

   Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart, Germany