Development of a Silk Fibroin‐Small Intestinal Submucosa Small‐Diameter Vascular Graft with Sequential VEGF and TGF‐β1 Inhibitor Delivery for In Situ Tissue Engineering

Abstract

Proper endothelialization and limited collagen deposition on the luminal surface after graft implantation plays a crucial role to prevent the occurrence of stenosis. To achieve these conditions, a biodegradable graft with adequate mechanical properties and the ability to sequentially deliver therapeutic agents isfabricated. In this study, a dual‐release system is constructed through coaxial electrospinning by incorporating recombinant human vascular endothelial growth factor (VEGF) and transforming growth factor β1 (TGF‐β1) inhibitor into silk fibroin (SF) nanofibers to form a bioactive membrane. The functionalized SF membrane as the inner layer of the graft is characterized by the release profile, cell proliferation and protein expression. It presents excellent biocompatibility and biodegradation, facilitating cell attachment, proliferation, and infiltration. The core‐shell structure enables rapid VEGF release within 10 days and sustained plasmid delivery for 21 days. A 2.0‐mm‐diameter vascular graft is fabricated by integrating the SF membrane with decellularized porcine small intestinal submucosa (SIS), aiming to facilitate the integration process under a stable extracellular matrix structure. The bioengineered graft is functionalized with the sequential administration of VEGF and TGF‐β1, and with the reinforced and compatible mechanical properties, thereby offers an orchestrated solution for stenosis with potential for in situ vascular tissue engineering applications.

Decellularized extracellular matrix-based composite scaffolds for tissue engineering and regenerative medicine

“…In another case, Liu et al . [ 170 ] combined SF membrane encapsulating different growth factors (TGF-β1 and VEGF) with dECM membrane as a composite vascular graft by coaxial aqueous electrospinning. The combination of dual growth factors in one membrane was used for promoting endothelialization and preventing collagen over-deposition, indicating the potential for vascular tissue engineering applications.…”

Surface Functionalization of Electrospun Scaffolds by QK-AG73 Peptide for Enhanced Interaction with Vascular Endothelial Cells

“…Constructing a confluent functional endothelium has been considered an attractive strategy to improve the biocompatibility of blood-contacting biomaterials, especially for small-diameter vascular grafts (<6 mm in diameter), which remain challenged with low long-term patency rates due to endothelial loss-induced thrombosis and intimal hyperplasia . Numerous strategies have been developed to improve endothelialization of these blood-contacting surfaces, among which growth factors such as vascular endothelial growth factor (VEGF) played a crucial role in vascularized tissue regeneration due to its potent angiogenic activity and promotion of endothelialization. − However, the use of growth factors usually faces issues related to safety, stability, and cost-effectiveness. , Alternatively, biomimetic peptides composed of natural amino acids hold great promise for their relatively low cost and good stability, ease of synthesis, high bioactivity, and minimized immunogenicity. − …”