Microconvex Dot-Featured Silk Fibroin Films for Promoting Human Umbilical Vein Endothelial Cell Angiogenesis via Enhancing the Expression of bFGF and VEGF

Abstract

Insufficient vascularization of grafts often leads to delayed tissue ingrowth and impaired tissue function in tissue engineering. The surface topography of grafts plays critical roles in angiogenesis. In the present study, we prepared silk fibroin (SF)based microtopography films with the number of convex dots ranging from 37 to 4835/mm 2 . The convex dot-featured topography surfaces were characterized by scanning electron microscopy, a Profilm3D optical profilometer, atomic force microscopy, and a contact angle goniometer. The effect of microtopographic films on the proliferation, adhesion, and expression of angiogenic factors of human umbilical vein endothelial cells (HUVECs) was investigated. Our results demonstrated that the SF film surface with 2899 convex dots/ mm 2 significantly enhanced adhesion, viability, and levels of vascular endothelial growth factors and basic fibroblast growth factors of HUVECs and significantly downregulated the level of α-SMA in human aortic smooth muscle cells, indicating that the microtopographic films could promote angiogenesis. Furthermore, in vitro results showed that HUVEC proliferation was positively correlated with yes-associated protein (YAP) activation, suggesting that the enhanced angiogenesis was mediated via the YAP pathway. Finally, mice subcutaneous embedding model results indicated that the SF film surface with 2899 convex dots/mm 2 could significantly enhance angiogenesis in vivo. Altogether, our results showed that the SF film surface with 2899 convex dots/mm 2 promoted the angiogenesis of HUVECs and offered a novel angiogenesis-promoting strategy of implant surface design for tissue engineering.

Bioinspired silk fibroin materials: From silk building blocks extraction and reconstruction to advanced biomedical applications

“…8 C. Moreover, this regulated gene expression process was proved to be associated with cell shape-regulated Yes-associated protein (YAP) activation. In vivo mouse subcutaneous implantation of the films also confirmed the angiogenesis enhancing effect of this proper convex dot-featured RSF film [ 128 ]. This study offered an effective method in angiogenesis-promotable material modification in tissue engineering.…”

“…Copyright 2020, Hindawi Ltd. Image (C) was modified with permission [ 128 ]. Copyright 2021, American Chemical Society.…”

“…For example, Tang et al. fabricated microconvex dots featured RSF films with the density ranging from 37 to 4835 dots/mm 2 [ 128 ], as schematically illustrated in Fig. 8 C. It indicated that the cells presented spindle shapes on the surface with lower convex dots density and satellite shapes on the surface with higher density.…”

Fabrication of konjac glucomannan‐silk fibroin based biomimetic scaffolds for improved vascularization and soft tissue engineering applications

“…SF has also been combined with other polymers to manufacture composite scaffolds that have promoted desirable cellular behavior 35–37 . Of particular interest is the potential of SF, either solo or in combination with other materials, to promote angiogenesis 38 . Li et al reported an enhancement in the formation of bone on three‐dimensional SF scaffolds triggered by the angiogenic and osteogenic differentiation of human amniotic mesenchymal stem cells 39 .…”

“…Tang et al explored the efficacy of micro‐patterned SF films in promoting the angiogenesis of human umbilical vein endothelial cells. They found that the angiogenic effect of the films was mediated through the expression of basic fibroblast growth factor and vascular endothelial growth factor 38 . Watchararot et al studied the angiogenic effect of SF scaffolds on a chick chorioallantoic membrane (CAM) 41 .…”