Silk Fibroin as Adjuvant in the Fabrication of Mechanically Stable Fibrin Biocomposites

Abstract

Fibrin is a very attractive material for the development of tissue-engineered scaffolds due to its exceptional bioactivity, versatility in the fabrication, affinity to cell mediators; and the possi-bility to isolate it from blood plasma, making it autologous. However, fibrin application is greatly limited due to its low mechanical properties, fast degradation, and strong contraction in the pres-ence of cells. In this study, we present a new strategy to overcome these drawbacks by combining it with another natural polymer: silk fibroin. Specifically, we fabricated biocomposites of fibrin (5 mg/mL) and silk fibroin (0.1, 0.5 and 1% w/w) by using a dual injection system, followed by ethanol annealing. The shear elastic modulus increased from 23 ± 5 Pa from fibrin alone, to 67 ± 22 Pa for fibrin/silk fibroin 0.1%, 241 ± 67 Pa for fibrin/silk fibroin 0.5% and 456 ± 32 Pa for fibrin/silk fibroin 1%. After culturing for 27 days with strong contractile cells (primary human arterial smooth muscle cells), fibrin/silk fibroin 0.5% and fibrin/silk fibroin 1% featured minimal cell-mediated contraction (ca. 15 and 5% respectively) in contrast with the large surface loss of the pure fibrin scaffolds (ca. 95%). Additionally, the composites enabled the formation of a proper endothelial cell layer after culturing with human primary endothelial cells under standard culture conditions. Overall, the fi-brin/silk fibroin composites, manufactured within this study by a simple and scalable biofabrication approach, offer a promising avenue to boost the applicability of fibrin in tissue engineering.