Design strategies for small diameter vascular grafts are converging toward native-inspired tissue engineered grafts. A new automated technology is presented that combines a dip-spinning methodology for depositioning concentric cell-laden hydrogel layers, with an adapted solution blow spinning (SBS) device for intercalated placement of aligned reinforcement nanofibres. This additive manufacture approach allows the assembly of bio-inspired structural configurations of concentric cell patterns with fibres at specific angles and wavy arrangements. The middle and outer layers were tuned to structurally mimic the media and adventitia layers of native arteries, enabling the fabrication of small bore grafts that exhibit the J-shape mechanical response and compliance of human coronary arteries. This scalable automated system can fabricate cellularized multilayer grafts within 30 min. Grafts were evaluated by hemocompatibility studies and a preliminary in vivo carotid rabbit model. The dip-spinning-SBS technology generates constructs with native mechanical properties and cell-derived biological activities, critical for clinical bypass applications.
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We want to thank all the researchers in the Cells for Cells, Dr. Valenzuela (Pontificia Universidad Católica de Chile), the Bio-Active Materials group (The University of Manchester, UK) and Dr. García’s (Universidad de Santiago de Chile) laboratories for insightful discussions and suggestions. We thank Dr. Gowsihan Poologasundarampillai for assistance with synchrotron-CT and the Diamond Light Source for beamtime (MT15507) on the I13 Diamond-Manchester Branchline and the staff there for all of the assistance with data collection. This work was made possible by the facilities and support provided by the Diamond-Manchester Collaboration and the Research Complex at Harwell, funded in part by the Engineering and Physical Sciences Research Council (EPSRC) (EP/M023877/1). We acknowledge financial support from CORFO 18COTE-97983, FONDEF IDEA I15I10545, CONICYT by the grants FONDECYT Nos 3160680, 1170608, FONDEQUIP EQM130028 and Newton-Picarte REDES No. 140144 and the Universidad de los Andes PMI program UAN1301.
© 2019, The Author(s).