Engineered Microvessel Fabrication via Dynamic Culture
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Solution Overview
Problem
Current methods for preparing engineered microvessels face challenges such as differences in physiological properties, difficulty in achieving a micro-scale inner diameter, and instability of the self-formed vascular lumen structure due to endothelial cell apoptosis.
Innovation Solution
A method involving the mixing of thrombin, vascular endothelial cells, cardiomyocytes, and a mixed culture medium with fibrinogen and collagen to create a gel pre-polymerisation solution, which is then cured to form an engineered microvessel entity. This entity is subjected to static and dynamic cultures to promote the formation and maintenance of a stable microvascular network.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Shape
If biological or polymer materials are used to create an engineered vessel with a tubular structure, then the structural similarity to real blood vessels is improved, but the physiological properties (stiffness and elasticity) deteriorate due to lack of cellular attachment
Solution Approach 1:
The patent combines biological materials (fibrinogen, collagen) with living cells (endothelial cells, smooth muscle cells, fibroblasts) to create a hybrid construct that maintains both structural integrity and physiological functionality. The biological materials provide the tubular framework while the cellular components confer natural physiological properties including stiffness, elasticity, and contractility.
Solution Approach 2:
The engineered microvessel is constructed as a composite system comprising extracellular matrix proteins (fibrinogen, collagen) and multiple cell types. This composite structure integrates the structural advantages of biological materials with the functional capabilities of living cells, achieving both shape fidelity and physiological reliability.
2Shape
If decellularization is performed on an engineered microvessel from a donor, then the structural framework is obtained, but the ability to endothelialize deteriorates
Solution Approach 1:
Instead of decellularizing after construction, the patent performs preliminary endothelialization during the construction phase by incorporating endothelial cells into the vessel wall from the beginning. This preliminary action ensures the vessel remains endothelialized throughout the process, eliminating the need for subsequent endothelialization steps.
3Shape
If self-formed vascular lumen structure is created by endothelial cells, then the lumen formation occurs, but the structure becomes unstable and collapses over time due to endothelial cell apoptosis
Solution Approach 1:
The patent applies different cell types to specific locations within the vessel wall: endothelial cells are positioned at the luminal surface to maintain lumen integrity, while smooth muscle cells and fibroblasts are placed in the outer layers to provide structural support. This localized cell distribution ensures both lumen formation and structural stability.
Solution Approach 2:
The patent merges multiple cell types (endothelial cells, smooth muscle cells, fibroblasts) into a single engineered vessel construct. The endothelial cells form and maintain the lumen structure, while the smooth muscle cells and fibroblasts provide mechanical support and prevent collapse, creating a stable composite structure.
4Manufacturing precision
If equipment precision is increased to achieve micro-scale inner diameter, then the manufacturing precision is improved, but the device complexity and cost increase
Solution Approach 1:
The patent controls the inner diameter by adjusting parameters of the gel pre-polymerisation solution, including fibrinogen concentration (2.5-10 mg/mL), collagen concentration (0.1-0.5 mg/mL), and cell densities. By varying these biochemical parameters, micro-scale diameters are achieved without requiring complex microfabrication equipment.
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
The method results in engineered microvessels with improved physiological characteristics, including stiffness, elasticity, and perfusability, which can maintain a stable microvascular structure for an extended period.
Implementation Method 1
obtaining a gel pre-polymerisation solution by mixing the first dispersion and the second dispersion, and obtaining a cellular entity by curing the gel pre-polymerisation solution
Implementation Method 2
The engineered microvessels are subjected to a pulsatile tensile stress generated by the contraction of the cardiomyocytes
Implementation Method 3
The engineered microvessels are then dynamically cultured in the mixed culture medium to form a microvascular network
Data Source
AI summary
A method for preparing an engineered microvessel is provided. The method includes: obtaining a first dispersion by mixing a thrombin solution, a vascular endothelial cell suspension, a cardiomyocyte suspension, and a portion of a mixed culture medium, and obtaining a second dispersion by mixing a fibrinogen solution, a collagen solution, and another portion of the mixed culture medium, wherein the mixed culture medium includes a vascular endothelial cell culture medium and a cardiomyocyte culture medium; obtaining a gel pre-polymerisation solution by mixing the first dispersion and the second dispersion, and obtaining a cellular entity by curing the gel pre-polymerisation solution; and obtaining an engineered microvascular entity by placing the cellular entity in the mixed culture medium at a static status for static culture, and then placing the cellular entity in the mixed culture medium at a flowing status for dynamic culture.