Embossed Membranes with Vascular Patterns Guide Vascularization in a 3D Tissue Model

Abstract

The vascularization of three-dimensional (3D) tissue constructs is necessary for transporting nutrients and oxygen to the component cells. In this study, a vacuum forming method was applied to emboss a vascular pattern on an electrospun membrane so that guided vascular structures could develop within the construct. Two- or six-layer constructs of electrospun membranes seeded with endothelial cells and pericytes were stacked and subcutaneously implanted into mice. Blood vessel formation in the implanted constructs with six alternating layers of flat membranes and membranes embossed with a blood vessel pattern was observed after two weeks of implantation. The formation of blood vessels was observed along the embossed blood vessel pattern in the structure of the embossed membrane laminated at four weeks and eight weeks. Vascular endothelial growth factor (VEGF) and angiopoietin 1 (Ang-1) were highly expressed in the vascularized structures. Therefore, we demonstrated that a structure capable of producing a desired blood vessel shape with electrospun membranes embossed with a blood vessel pattern can be manufactured, and that a variety of structures can be manufactured using electrospun membranes in the tissue engineering era.

Electrospun Nanofibers for Improved Angiogenesis: Promises for Tissue Engineering Applications

“…The results obtained from confocal microscopy showed an embossed vascular pattern (208.8 ± 44.5 µm in height) up to 3 days post-cell culture. New blood vessel formation and maturation were also confirmed by the upregulation of VEGF and Ang-1 genes in the 6x embossed group [204]. Furthermore, co-culturing of ECs with bone and adipose tissue derived mesenchymal stem cells (BM-MSCs and AD-MSCs) led to promoted endothelial tubulogenesis [205].…”

“…Despite recent advancements of iPSCs in the field of regenerative medicine, a lack of investigation still remains a pressing issue for the use of this cell type in angiogenesis-stimulant nanofibrous mats. Green: Ang-1, red: HUVEC, blue: DAPI (adapted from Hong et al [204]). PCL, poly(ε-caprolactone); EC, endothelial cell.…”

“…( C ) Immunofluorescence images exhibiting differences in angiopoietin 1 (Ang-1) expression in cross-sections of different groups after 1, 2, 4, and 8 weeks of surgery; dashed lines show the edge of transplanted embossed sheets. Green: Ang-1, red: HUVEC, blue: DAPI (adapted from Hong et al [ 204 ]). PCL, poly(ε-caprolactone); EC, endothelial cell.…”

Organ-on-a-chip: recent breakthroughs and future prospects

“…OOAC technology has developed rapidly in recent years and has enhanced our knowledge of all the major organs. Others not discussed in this review include blood vessels [99,114,115], the skin [116,117], the BBB [118,119], skeletal muscle [120,121], and the CNS [122,123].…”

Assessment of the Release of Vascular Endothelial Growth Factor from 3D-Printed Poly-ε-Caprolactone/Hydroxyapatite/Calcium Sulfate Scaffold with Enhanced Osteogenic Capacity

“…In addition, it was also reported that their structures are able to mimic native bones and can effectively help bone repair. For instance, the microstructure of bioceramics allow it to have the ability to promote ossification and neovascularization, and such abilities are critical for osteoinduction, osteoconduction and osseointegration [5]. In recent years, bioceramics combined with three-dimensional (3D) printing is starting to become a popular trend due to its excellent customization, biocompatibility and bioactivity [6].…”