Bioengineered Vascular Network for Thick Tissue Perfusion
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Solution Overview
Problem
Current vascularization strategies for engineered tissues are insufficient for thick tissues as they rely on classical angiogenesis paradigms, which are inadequate for providing a functional vascular network, limiting engineered tissues to thin scales.
Innovation Solution
Development of an in vitro vasculogenic technology using spherical organoids comprising endothelial cells and mesenchymal stem cells embedded in a hydrogel, promoting a multiscale and multiphenotype vascular network with arterial, microvascular, and venous components, capable of distributing energy and mass flow to parenchymal cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If classical angiogenesis paradigm is used with endothelial cells and mural cells, then vascular network can be established in thin tissues, but the vascular network is insufficient for thick engineered tissues
Solution Approach 1:
The invention segments the vascular network into hierarchical levels: macrovascular structures (mm to cm scale) formed by self-assembly of vascular cells in biodegradable scaffolds, and microvascular networks (micrometer scale) formed by endothelial cell sprouting. This segmentation allows each level to address different perfusion requirements, enabling thick tissue vascularization that classical single-scale approaches cannot achieve.
Solution Approach 2:
The invention transitions from two-dimensional monolayer cell cultures to three-dimensional self-assembled vascular structures. The macrovascular networks are constructed in 3D space within biodegradable scaffolds, allowing spatial organization and perfusion pathways that cannot be achieved in planar configurations, thereby supporting thick tissue dimensions.
2Length of stationary object
If engineered tissue thickness is increased for clinical effectiveness, then meaningful clinical effect is achieved, but sufficient vascularization becomes insufficient
Solution Approach 1:
The invention implements preliminary action by pre-forming self-assembled macrovascular networks within biodegradable scaffolds before tissue implantation. These pre-established vascular structures provide immediate perfusion pathways upon implantation, eliminating the lag time associated with de novo angiogenesis in thick tissues and ensuring adequate vascularization from the outset.
Solution Approach 2:
The invention employs a nested hierarchical structure where microvascular networks (formed by endothelial cell sprouting) are nested within and extend from macrovascular structures (self-assembled in scaffolds). This nested architecture allows the microvascular network to access and perfuse deep tissue regions while the macrovascular network provides main perfusion pathways, collectively supporting thick tissue dimensions.
3Length of stationary object
If multi-scale and multi-phenotype vascular network is created, then perfusion to thick tissues is achieved, but device complexity increases
Solution Approach 1:
The invention utilizes self-service mechanisms where vascular cells (endothelial cells, pericytes, smooth muscle cells) spontaneously self-assemble into macrovascular structures within biodegradable scaffolds without external guidance patterns. The endothelial cells then autonomously sprout microvascular networks in response to physiological cues. This self-organization reduces manufacturing complexity compared to techniques requiring precise micropatterning or external control systems.
Solution Approach 2:
The invention leverages parameter changes in cell behavior and material properties: biodegradable scaffolds transition from providing structural support to degrading and releasing vascular cells, which then undergo phenotypic changes from undifferentiated states to specialized vascular cell types. These parameter changes enable the formation of complex multi-scale vascular networks through natural biological processes rather than complex engineering controls.
Data Source
AI summary
Provided herein is technology relating to engineered tissues and particularly, but not exclusively, to methods, compositions, and systems for engineering a biosynthetic vascular network.