Fabrication of highly interconnected porous silk fibroin scaffolds for potential use as vascular grafts

• Published in: Acta biomaterialia Vol. 10; no. 5; pp. 2014 - 2023
• Main Authors: Zhu, Meifeng, Wang, Kai, Mei, Jingjing, Li, Chen, Zhang, Jiamin, Zheng, Wenting, An, Di, Xiao, Nannan, Zhao, Qiang, Kong, Deling, Wang, Lianyong
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2014
• Subjects: Alcohols - pharmacology; Animals; Blood Vessel Prosthesis; Bombyx; Cell Adhesion - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; Compressive Strength - drug effects; Fibroins - pharmacology; Freeze-drying; Freezing; Heparin; Heparin - pharmacology; Humans; Materials Testing - methods; Mice; Microscopy, Electron, Scanning; Myocytes, Smooth Muscle - cytology; Myocytes, Smooth Muscle - drug effects; Neovascularization; Neovascularization, Physiologic - drug effects; Porosity; Prothrombin Time; Silk fibroin scaffolds; Spectroscopy, Fourier Transform Infrared; Tissue Scaffolds - chemistry; Vascular graft; Neovascularization; Heparin; Freeze-drying; Vascular graft; Silk fibroin scaffolds
• ISSN: 1742-7061; 1878-7568; 1878-7568
• DOI: 10.1016/j.actbio.2014.01.022

In this study, an easy-to-adopt and mild approach based on modified freeze-drying method was developed to fabricate a silk fibroin (SF) scaffold with high porosity, proper pore size and highly interconnected pores. The preparation conditions were optimized by pre-selecting the freezing temperature, SF concentrations, the choice of various alcohols as solvent and its working concentrations. Heparin was also successful incorporated into SF scaffold. The heparin-loaded SF scaffolds exhibited excellent anticoagulant property, cell infiltration and in vivo capillary formation, implicating a promising potential use as vascular grafts. Silk fibroin (SF) scaffolds have been designed and fabricated for multiple organ engineering owing to SF’s remarkable mechanical property, excellent biocompatibility and biodegradability, as well as its low immunogenicity. In this study, an easy-to-adopt and mild approach based on a modified freeze-drying method was developed to fabricate a highly interconnected porous SF scaffold. The physical properties of the SF scaffold, including pore morphology, pore size, porosity and compressive modulus, could be adjusted by the amount of ethanol added, the freezing temperature and the concentration of SF. Fourier transform infrared spectroscopy illustrated that treatment of the lyophilized scaffolds with 90% methanol led to a structure transition of SF from silk I (random coil) to silk II (beta-sheet), which stabilized the SF scaffolds in water. We also incorporated heparin during fabrication to obtain a heparin-loaded scaffold which possessed excellent anticoagulant property. The heparin that was incorporated into the SF scaffolds could be released in a sustain manner for approximately 7days, inhibiting the proliferation of human smooth muscle cells within the scaffold in vitro while promoting neovascularization in vivo. We therefore propose that the SF porous scaffold fabricated here may be an attractive candidate for use as a potential vascular graft for implantation based on its high porosity, excellent blood compatibility and mild fabrication process.