Biomimetic Vascular Network for Tissue Engineering
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Solution Overview
Problem
Current tissue engineering techniques face challenges in creating artificial organs with a vascular network that mimics natural organs, leading to issues with oxygen and nutrient delivery, resulting in organ malfunction and thrombosis, especially in tissue-engineered solid organs like livers and kidneys.
Innovation Solution
The development of a biomimetic vascular network using a substrate with channels designed according to Murray's law, where the height and width of channels vary to optimize fluid dynamics, shear stress, and velocity, and a semi-permeable membrane for cell-to-cell signaling, replicating the physiological structure of natural blood vessels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If cells are grown in a three-dimensional container near a blood vessel, then the structure is simple and easy to implant, but only cells in close proximity to the blood vessel will survive due to limited diffusion distance of oxygen and nutrients
Solution Approach 1:
The vascular network is segmented into multiple hierarchical levels (arteries, arterioles, capillaries, venules, veins) with progressively smaller diameters, allowing oxygen and nutrients to reach cells at increasing distances from the main blood vessel while maintaining manageable structural complexity
Solution Approach 2:
The vascular network transitions from a two-dimensional surface structure to a three-dimensional hierarchical branching structure, enabling cells throughout the volume of the tissue to be within diffusion distance of a vessel while maintaining overall structural simplicity for implantation
2Reliability
If a vascular network is designed from inlet vessels to smallest vessels to perfuse parenchymal cells, then oxygen and nutrient delivery is improved, but the device complexity increases
Solution Approach 1:
The vascular network parameters (vessel diameter, wall thickness, branching angles) are systematically changed according to Murray's law at each hierarchical level, optimizing fluid dynamics and shear stress while following natural physiological patterns to reduce complexity
Solution Approach 2:
The vascular network copies the physiological branching patterns and structural organization of natural blood vessels, utilizing established biological design principles to create an efficient network without requiring complex artificial engineering solutions
3Reliability
If channels are designed according to Murray's law with varying height and width, then fluid dynamics and shear stress are optimized, but manufacturing precision requirements increase
Solution Approach 1:
Channel dimensions (height and width) are systematically varied according to Murray's law parameters, creating a gradient structure that optimizes fluid dynamics and shear stress while following mathematical relationships that simplify manufacturing compared to arbitrary dimension changes
Solution Approach 2:
The channel design copies natural blood vessel geometry and dimensional relationships, utilizing physiological design principles that have been optimized by evolution, thereby reducing the need for complex manufacturing precision requirements
4Reliability
If a thick solid organ is created with adequate blood vessel proximity to parenchymal cells, then organ function is sustained, but the organ volume and implantation complexity increase
Solution Approach 1:
The organ is conceptually segmented into functional units (lobules) surrounded by vascular networks, allowing each unit to be independently perfused and function autonomously, thereby sustaining overall organ function without requiring excessive total volume
Solution Approach 2:
The vascular network utilizes three-dimensional branching to penetrate deep into the organ tissue, ensuring that cells throughout the organ volume (not just at the surface) are within diffusion distance of blood vessels, thereby sustaining organ function without increasing overall organ size
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
This approach enables the creation of tissue-engineered organs with improved oxygen and nutrient delivery, reduced thrombosis, and sustained function, addressing the limitations of existing vascular networks in artificial organs.
Implementation Method 1
The diffusion distance of oxygen and nutrients from a blood vessel through tissue is very short (e.g., a few hundred microns)
Implementation Method 2
a semi-permeable membrane for cell-to-cell signaling
Data Source
AI summary
The invention provides method of fabricating a scaffold comprising a fluidic network, including the steps of: (a) generating an initial vascular layer for enclosing the chamber and providing fluid to the cells, the initial vascular layer having a network of channels for fluid; (b) translating the initial vascular layer into a model for fluid dynamics analysis; (c) analyzing the initial vascular layer based on desired parameters selected from the group consisting of a characteristic of a specific fluid, an input pressure, an output pressure, an overall flow rate and combinations thereof to determine sheer stress and velocity within the network of channels; (d) measuring the sheer stress and the velocity and comparing the obtained values to predetermined values; (e) determining if either of the shear stress or the velocity are greater than or less than the predetermined values, and (f) optionally modifying the initial vascular layer and repeating steps (b)-(e). The invention also provides compositions comprising a vascular layer for use in tissue lamina as well as a medical devices having a vascular layer and kits.