Leaf-inspired microcontact printing vascular patterns

Abstract

The vascularization of tissue grafts is critical for maintaining viability of the cells within a transplanted graft. A number of strategies are currently being investigated including very promising microfluidics systems. Here, we explored the potential for generating a vasculature-patterned endothelial cells that could be integrated into distinct layers between sheets of primary cells. Bioinspired from the leaf veins, we generated a reverse mold with a fractal vascular-branching pattern that models the unique spatial arrangement over multiple length scales that precisely mimic branching vasculature. By coating the reverse mold with 50 μg ml of fibronectin and stamping enabled selective adhesion of the human umbilical vein endothelial cells (HUVECs) to the patterned adhesive matrix, we show that a vascular-branching pattern can be transferred by microcontact printing. Moreover, this pattern can be maintained and transferred to a 3D hydrogel matrix and remains stable for up to 4 d. After 4 d, HUVECs can be observed migrating and sprouting into Matrigel. These printed vascular branching patterns, especially after transfer to 3D hydrogels, provide a viable alternative strategy to the prevascularization of complex tissues.

A Facile Strategy for Fabricating Tissue Engineering Scaffolds with Sophisticated Prevascularized Networks for Bulk Tissue Regeneration

“…The distribution of vasculature is complex for bulk tissue. The vascular structure in tissues is hierarchical and resembles tree branches . Thus, the multi‐level bifurcation morphology and spatial degree have already exceeded those of a lot of previous research of hydrogel vascularization scaffolds .…”

“…The vascular structure in tissues is hierarchical and resembles tree branches. [10,38,39] Thus, the multi-level bifurcation morphology and spatial degree have already exceeded those of a lot of previous research of hydrogel vascularization scaffolds. [4,23,26,47] In addition, the compressive strength values of four different branch spatial gelation scaffold (Table 1), respectively.…”

“…The final shape and spatial structure of the channels in the engineered scaffolds is limited to the receiving platform. The structures of tissues and organs are complex; normal adult vasculature systems present as a hierarchical vascular structure with different multi‐level branched networks, and the distribution shape of vasculature like as the leaf skeleton . From the above, autonomous spatial distribution and multi‐level branched structures are two basic issue, which should be addressed in fabricating the prevascularized network construct ( Figure ).…”

“…The structures of tissues and organs are complex; normal adult vasculature systems present as a hierarchical vascular structure with different multi-level branched networks, [34][35][36][37] and the distribution shape of vasculature like as the leaf skeleton. [10,38,39] From the above, autonomous spatial distribution and multi-level branched structures are two basic issue, which should be addressed in fabricating the prevascularized network construct (Figure 1). Therefore, there is still the need to develop a novel approach able to produce sophisticated multi-level branched prevasculature architectures within hydrogel scaffolds for production of 3D constructs with spatial structure for specific bulk tissue engineering applications.…”

Advanced Bottom‐Up Engineering of Living Architectures

“…Precisely engineered culturing and harvesting substrates can direct the spatial arrangement of different cell populations in cell sheets design, contributing toward more complex and in vivo‐like assemblies. In this context, straightforward approaches such as microcontact printing of ECM proteins using rationally designed stamps have been explored to enable spatial control over cellular adhesion layouts during cell sheet manufacturing . By controlling nonadhesive and cell adhesive areas, researchers engineered hepatocyte modules surrounded by endothelial cells, achieving a co‐patterned liver‐like microtissue that maintained the ability to synthesize albumin and urea ( Figure A,B) .…”