Glycerol-plasticized silk fibroin vascular grafts mimic key mechanical properties of native blood vessels.

Cardiovascular diseases are a major global health challenge. Blood vessel disease and dysfunction are major contributors to this healthcare burden, and the development of tissue-engineered vascular grafts (TEVGs) is required, particularly for the replacement of small-diameter vessels. Silk fibroin (SF) is a widely used biomaterial for TEVG fabrication due to its high strength and biocompatibility. However, the stiffness of SF is much higher than that of native blood vessels (NBVs), which limits its application for vascular tissue engineering. In this study, SF was plasticized with glycerol to produce TEVGs exhibiting similar stiffness and ultimate tensile strength to those of NBVs. The electrospun SF/glycerol TEVGs exhibited mechanical properties comparable to NBVs and supported the in vitro proliferation of essential vascular cells-endothelial and smooth muscle cells. After 5 days of culture, the TEVGs exhibited an endothelial monolayer in the lumen, demonstrating their potential for functional vascular tissue regeneration. Our study demonstrates the feasibility of producing TEVGs from SF with tailored mechanical properties, paving the way for more functional and durable TEVGs for future clinical applications.

Spontaneous Orthogonal Alignment of Smooth Muscle Cells and Endothelial Cells Captures Native Blood Vessel Morphology in Tissue-Engineered Vascular Grafts.

Tissue-engineered vascular grafts (TEVGs) have emerged as a potential alternative to autologous grafts for replacing small-diameter blood vessels during bypass surgery. The axial alignment of endothelial cells (ECs) and the circumferential alignment of smooth muscle cells (SMCs) are crucial for functional native blood vessels (NBVs). However, achieving this cellular alignment in TEVGs remains a formidable challenge. In this study, TEVGs were developed using a low-cost technique that aligned ECs axially and SMCs circumferentially within hours. The TEVGs comprised an electrospun polycaprolactone (PCL) layer and a gelatin methacryloyl (GelMA) cast layer. A freezing-induced alignment technique was developed that partially aligns the electrospun fibers axially, thereby promoting rapid axial alignment of ECs. Furthermore, SMCs cultured in a GelMA layer with intermediate stiffness (5-12 kPa) surrounding a PCL tube could promote conformation of the SMCs to the curvature of the PCL tube, resulting in their spontaneous circumferential alignment. Additionally, the TEVGs demonstrated mechanical properties similar to those of NBVs, which could facilitate future translation. This approach represents a significant advance in tissue engineering, enabling the fabrication of TEVGs with appropriate mechanical properties that recapitulate key NBV cell structural features within hours using a scalable and accessible method.