Vascularized Tissue Chip Layout for In Vitro Microvasculature
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Solution Overview
Problem
Current 3D cell/tissue cultures fail to recreate the biological microvasculature for nutrient delivery, oxygen transport, and metabolic waste removal, making it difficult to mimic the dynamic 3D microenvironment found in vivo.
Innovation Solution
A chip and system designed to produce vascularized tissues by incorporating a culture chamber, inflow and outflow channels, side channels with V-shape bent sections, and reservoirs, utilizing endothelial and stromal cells, and hydrogels to form vascular networks in vitro, with controlled medium flow and rotation to promote neovessel formation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If 3D cell/tissue cultures are used to provide tissue-specific architecture and complex cellular interactions, then the accuracy of in vivo conditions is improved, but the ability to recreate biological microvasculature for nutrient delivery and waste removal deteriorates
Solution Approach 1:
The device segments the culture system into distinct functional zones: a culture chamber for 3D tissue cultivation, side channels for vascular network formation, and reservoirs for medium supply. This segmentation allows independent optimization of tissue culture conditions and vasculature development, resolving the contradiction between maintaining 3D tissue architecture and recreating functional microvasculature.
Solution Approach 2:
The invention implements a nested structure where microvasculatures are formed within the 3D tissue culture system. The side channels with porous walls are positioned adjacent to the culture chamber, allowing endothelial cells to migrate and form vascular networks that are embedded within the 3D tissue matrix, creating a hierarchical nested arrangement of vasculature within tissue.
2Quantity of substance
If microfluidics are integrated as synthetic capillaries in 3D cell/tissue cultures, then nutrient delivery is improved, but the dynamic 3D microenvironment simulation deteriorates
Solution Approach 1:
The device employs dynamic culture medium flow through the side channels and reservoirs to simulate physiological conditions. The continuous flow of medium through the vascular network creates dynamic shear stress and flow patterns that mimic in vivo blood flow, enabling the 3D tissue culture to adapt and respond to physiologically relevant mechanical stimuli while maintaining nutrient delivery.
Solution Approach 2:
The invention utilizes hydraulic principles by implementing a fluid-based vascular network through side channels connected to reservoirs. Culture medium is pumped through this hydraulic system to deliver nutrients and remove waste, creating a pressure-driven flow system that replicates the hydraulic function of biological microvasculature within the 3D tissue culture environment.
3Reliability
If a complex chip structure with multiple channels and reservoirs is designed to produce vascularized tissues, then the vascular network formation is improved, but the device complexity increases
Solution Approach 1:
The chip structure is designed with multi-functionality where the side channels serve multiple purposes: they act as templates for vascular network formation, provide pathways for culture medium flow, and facilitate endothelial cell migration. The reservoirs simultaneously store culture medium and generate flow pressure. This multi-functionality reduces the need for additional dedicated components, thereby managing device complexity while maintaining vascular network formation capability.
Solution Approach 2:
The side channels incorporate porous wall sections that enable endothelial cells to migrate from the channel into the culture chamber, forming vascular networks. The porous structure provides a scaffold for cell attachment and migration while allowing medium permeation, thereby achieving vascularization through a relatively simple structural modification rather than complex multi-component assembly.
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 system effectively recreates vascular networks within 3D tissues, enabling precise simulation of nutrient delivery, oxygen transport, and metabolic waste removal, providing a more accurate model of in vivo conditions.
Implementation Method 1
each side channel has an upstream end, a V-shape bent section and a downstream end... two upstream reservoirs respectively connected to two upstream ends of the first and second side channels
Implementation Method 2
The pressure gradient in the culture chamber allows the 3D tissue to be cultured in a first space... and drives the formation of neovessels in a second space
Implementation Method 3
the inner surface of the V-shape bent section of each side channel is coated with a hydrophobic material, while the inner surface of the rest of the side channel is coated with a hydrophilic material
Implementation Method 4
the inner surface of the V-shape bent section of each side channel is coated with a hydrophobic material, while the inner surface of the rest of the side channel is coated with a hydrophilic material
Implementation Method 5
The chip is then rotated to generate a centrifugal force, so that the 3D tissue in the culture chamber is moved to a position farthest from the rotation center of the chip
Data Source
AI summary
Disclosed herein is a chip for producing vascularized tissues. According to some embodiments of the present disclosure, the chip comprises a loading chamber, a culture chamber, a fluid collection chamber, an inflow channel, at least one outflow channel, two side channels, two upstream reservoirs, and two downstream reservoirs. Also disclosed herein is a system comprising a pair of the present chips, and methods of producing vascularized tissues by using the present chip or system.