Dissolved Matrigel Capillary Fabrication for Vascular Viability
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Solution Overview
Problem
Current in vitro capillary fabrication devices are unable to rapidly create lumenized capillary networks with properties similar to in vivo networks, limiting their application in drug development and tissue engineering, especially for thicker, metabolically demanding organs like the heart and liver, due to limitations in forming controlled-geometry microvessels that can connect with host vessels and maintain vascularization.
Innovation Solution
The development of capillary fabrication devices that use a support-generating medium with a gel-forming material like Matrigel™, dissolved in a cell-culture medium, to form a thin support medium on a cell-culture surface, allowing for the formation of capillary networks with natural or controlled geometries and associated extracellular matrix and basement membrane, which enhances blood perfusion and viability of engineered tissues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If rapid quasi-two-dimensional Matrigel capillary fabrication devices are used, then capillary networks form quickly (1-3 days), but endothelial cells die within 24-48 hours and networks are not viable long-term
Solution Approach 1:
The patent changes the physical state of the Matrigel from solidified gel to dissolved/liquid form, fundamentally altering the culture environment. This parameter change allows endothelial cells to remain viable and form functional capillary networks for extended periods (at least 4 weeks) while maintaining rapid formation capabilities, resolving the contradiction between speed and long-term viability
2Ease of manufacture
If thick layer of Matrigel (0.5 mm) is used, then capillary networks can form, but cell motility is restricted and endothelial cells become abnormally elongated
Solution Approach 1:
The patent changes the concentration and physical state of Matrigel from thick solidified gel to diluted dissolved form. This creates a liquid culture medium that allows free cell motility and migration, enabling endothelial cells to form physiologically accurate, non-elongated morphologies while still supporting capillary network formation
3Productivity
If high concentration of growth factors in Matrigel is used, then capillary formation is promoted, but artifacts are generated and cells are over-stimulated
Solution Approach 1:
The patent extracts endothelial cells from the solidified Matrigel gel and suspends them in a liquid culture medium with controlled, physiological concentrations of growth factors. This separation eliminates the artifacts and over-stimulation caused by high concentrations of ECM-bound growth factors in solid Matrigel, producing artifact-free capillary networks with accurate physiological properties
4Productivity
If current in vitro angiogenesis techniques are used, then capillary networks can be formed, but they cannot rapidly create networks with properties similar to in vivo networks
Solution Approach 1:
The patent changes the culture system from solidified gel-based 2D/3D matrices to a dissolved Matrigel liquid medium system. This fundamental parameter change enables rapid capillary network formation (1-3 days) while simultaneously producing networks with physiologically accurate properties including proper endothelial cell morphology, connectivity, and in vivo-like functional characteristics
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
These devices produce capillary networks with morphological and functional properties similar to in vivo capillaries, maintaining viability for up to four weeks, enabling improved vascularization and blood perfusion in engineered tissues, and are suitable for high-throughput applications and tissue engineering of thicker organs.
Implementation Method 1
a gel forming material and a liquid cell-culture medium, wherein the gel forming material is substantially dissolved in the cell-culture medium
Implementation Method 2
forms a support medium on the cell-culture surface
Data Source
AI summary
Disclosed herein are capillary fabrication devices comprising living cells within a support medium. Culture of the cells produces viable lumenized capillary networks with natural or pre-determined geometries and ECM and basement membrane associated with the capillary networks. The capillary networks and the ECM and basement membrane detachable from the capillary networks are useful for tissue engineering applications.