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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Bioeng. Biotechnol. | doi: 10.3389/fbioe.2019.00356

Novel Silk Fibroin Tubular Scaffold for the Repair and Regeneration of Small Caliber Blood Vessels: from Design to In Vivo Pilot Tests

Antonio Alessandrino1,  Anna Chiarini2, Marco Biagiotti1, Ilaria Dal Prà2, 3,  Giulia A. Bassani1, Valentina Vincoli1, Piergiorgio Settembrini4, 5,  Pasquale Pierimarchi6,  Giuliano Freddi1* and  Ubaldo Armato2, 3
  • 1Independent researcher, Italy
  • 2Human Histology and Hembrology Unit, Department of Medicine, School of Medicine and Surgery, University of Verona, Italy
  • 3Human Histology and Hembrology Unit, Department of Medicine, School of Medicine and Surgery, University of Verona, Italy
  • 4Department of Vascular Surgery, San Carlo Borromeo Hospital, Italy
  • 5University of Milan, Italy
  • 6Institute of Traslational Pharmacology (CNR), Italy

Silk fibroin (SF) is an eligible biomaterial for the development of small caliber vascular grafts for substitution, repair, and regeneration of blood vessels. This study presents the properties of a newly designed multi-layered SF tubular scaffold for vascular grafting (SilkGraf). The wall architecture consists of two electrospun layers (inner and outer) and an intermediate textile layer. The latter was designed to confer high mechanical performance and resistance on the device, while electrospun layers allow enhancing its biomimicry properties and host's tissues integration. In vitro cell interaction studies performed with adult Human Coronary Artery Endothelial Cells (HCAECs), Human Aortic Smooth Muscle Cells (HASMCs), and Human Aortic Adventitial Fibroblasts (HAAFs) demonstrated that the electrospun layers favor cell adhesion, survival and growth. Once cultured in vitro on the SF scaffold the three cell types showed an active metabolism (consumption of glucose and glutamine, release of lactate), and proliferation for up to 20 days. HAAF cells grown on SF showed a significantly lower synthesis of type I procollagen than on polystyrene, meaning a lower fibrotic effect of the SF substrate. The cytokine and chemokine expression patterns were investigated to evaluate the cells’ proliferative and pro-inflammatory attitude. Interestingly, no significant amounts of truly pro-inflammatory cytokines were secreted by any of the three cell types which exhibited a clearly proliferative profile. Good hemocompatibility was observed by complement activation, hemolysis, and hematology assays. Finally, the results of an in vivo preliminary pilot trial on minipig and sheep to assess the functional behavior of implanted SF-based vascular graft identified the sheep as the more apt animal model for next medium-to-long term preclinical trials.

Keywords: silk fibroin, small caliber vascular graft, Morphological structure, mechanical performance, In vitro biocompatibility, in vivo pilot test

Received: 30 Jul 2019; Accepted: 08 Nov 2019.

Copyright: © 2019 Alessandrino, Chiarini, Biagiotti, Dal Prà, Bassani, Vincoli, Settembrini, Pierimarchi, Freddi and Armato. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Giuliano Freddi, Independent researcher, Lomazzo, Italy, giuliano@silkbiomaterials.com