Vascularization of engineered tissues using capillary morphogenesis and endothelialized microchannels within fibrin-collagen co-gels

Event Abstract Back to Event Vascularization of engineered tissues using capillary morphogenesis and endothelialized microchannels within fibrin-collagen co-gels Ross E. Fitzsimmons1, Mark A. Aquilino1, Ronald G. Ireland1 and Craig A. Simmons1, 2, 3 1 University of Toronto, Institute of Biomaterials and Biomedical Engineering, Canada 2 University of Toronto, Department of Mechanical and Industrial Engineering, Canada 3 University of Toronto, Faculty of Dentistry, Canada Introduction: Generating vascularized tissues by seeding endothelial cells (ECs) within microchannels formed in hydrogel scaffolds has the potential to bring high viability tissue constructs to fruition ex vivo. However, solely relying on EC-seeded channels results in tissues with only small artery/vein-like vessels and no capillaries. To avoid non-physiological tissue architectures and instead produce appropriate vessel hierarchies, we are exploring the strategy of eliciting sprouting from EC-seeded channels with the inclusion of angiogenesis-stimulating mesenchymal cells in the hydrogel. This strategy requires a hydrogel optimized to maintain mechanically stable tissues and vasculature while enabling EC sprouting. To this end, we investigated fibrin, collagen, and fibrin-collagen co-gels, as fibrin has the capacity to elicit EC capillary morphogenesis ex vivo and collagen has favorable mechanical properties advantageous for generating stable tissues. Materials and Methods: Scanning electron microscopy of critical point dried hydrogels was performed to assess fibril microstructure. EC-seeded microcarrier beads were encapsulated into hydrogels and co-cultured with bone marrow stromal cells (BMSCs) to assess biomaterial angiogenicity. Since minimizing gel contraction is critical for maintaining channel patency, contraction was assessed under unrestrained conditions using 200,000 BMSC/mL gel. Microchannels were formed by polymerizing gels around a nylon line threaded between needles within a silicone chamber. Once the line was removed, channels could then be seeded with ECs and perfused using syringe or peristaltic pumps. Results and Discussion: Co-gel microstructure resembled both collagen and fibrin, with collagen fibril diameters in the range of ~178-290 nm (Fig.1). Fibrin and co-gels elicited EC sprouting, whereas collagen alone elicited independent EC migration. Both fibrin and co-gels (2.5 mg/mL fibrin + 0.5-3.0 mg/mL collagen) were relatively resistant to cell-mediated contraction compared to collagen alone (p ≤ 0.001) (Fig. 2). However, fibrin alone could not support the formation of smooth, mechanically-robust channels, whereas collagen-fibrin co-gels produced smooth channels that withstood flow rates >100 mL/hr without channel warping, provided that collagen was ≥1.0 mg/mL. Finally, ECs were found to sprout outwards from the channels into the co-gels. Conclusion: The promising features of collagen-fibrin uncovered by this study suggest that such co-gels may be of value for generating vascularized constructs. To further investigate their potential, we have fabricated a custom 3D printer to produce collagen-fibrin constructs with branching channels. Currently, we are optimizing the 3D printing process in conjunction with examining the roles that pulsatile flow and shear stress have in vessel muscularization, with the aim of generating thick tissues with high viability and physiological vascular architectures. Keywords: Tissue Engineering, blood vessel, Bioprinting, 3D scaffold Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Biomaterials in constructing tissue substitutes Citation: Fitzsimmons RE, Aquilino MA, Ireland RG and Simmons CA (2016). Vascularization of engineered tissues using capillary morphogenesis and endothelialized microchannels within fibrin-collagen co-gels. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.02873 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Ross E Fitzsimmons Mark A Aquilino Ronald G Ireland Craig A Simmons Google Ross E Fitzsimmons Mark A Aquilino Ronald G Ireland Craig A Simmons Google Scholar Ross E Fitzsimmons Mark A Aquilino Ronald G Ireland Craig A Simmons PubMed Ross E Fitzsimmons Mark A Aquilino Ronald G Ireland Craig A Simmons Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.