Modular Bioreactor Vascularizing Tissue Constructs
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Solution Overview
Problem
Current tissue engineering strategies fail to pre-build a functional vasculature within tissue constructs, limiting their ability to efficiently diffuse oxygen and nutrients, and existing bioreactors do not provide sufficient perfusion paths for microvessels to form organized and functional networks.
Innovation Solution
A modular bioreactor system with upper, intermediate, and lower biochambers, each with inflow and outflow ports, allows for indirect and direct perfusion of tissue constructs, enabling the growth of a vascular network by positioning a tissue construct with a conduit in the intermediate biochamber and using flared connectors to maintain perfusion and maturity of vessels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Volume of moving object
If a tissue construct is made larger than a few millimeters, then it can provide more functional tissue volume, but oxygen and nutrients cannot efficiently diffuse into the construct cells from the external environment and surrounding host tissue
Solution Approach 1:
The bioreactor system divides the tissue construct into multiple segments or zones with different perfusion characteristics. The construct is organized into a three-dimensional network of channels that segment the tissue into perfusable units, allowing efficient nutrient and oxygen delivery throughout the entire volume while maintaining diffusion efficiency in each local segment.
Solution Approach 2:
The invention transitions from two-dimensional surface diffusion to three-dimensional internal perfusion. By incorporating a three-dimensional network of perfusion channels throughout the construct volume, the system enables efficient nutrient and oxygen delivery in all spatial dimensions, overcoming the diffusion limitation that only affects the outer surfaces of larger constructs.
2Quantity of substance
If existing bioreactors are used to build microvessels in vitro, then microvessel segments can be embedded in a three-dimensional collagen matrix, but the bioreactors fail to provide sufficient perfusion paths through the constructs such that flow through the construct is maintained and the microvessels segments subsequently propagate into an organized and functional network
Solution Approach 1:
The bioreactor system establishes perfusion paths and flow conditions before the microvessel segments need to propagate and organize. By pre-configuring the three-dimensional channel network and initiating perfusion flow beforehand, the system creates the necessary hydraulic and biochemical environment that guides and accelerates the self-organization of microvessel segments into functional networks.
Solution Approach 2:
The bioreactor introduces an intermediary perfusion system consisting of temporary channels and flow mechanisms that mediate between the external culture medium and the developing microvessel network. This intermediary perfusion system provides the necessary flow paths and biochemical gradients that enable microvessel segments to propagate and organize into functional networks without requiring direct external manipulation.
3Shape
If known methods and devices are used to build vessels in vitro, then microvessels can be built within a preformed scaffold, but the methods have not sufficiently addressed how to build an organized network of microvessels such that a particular construct can then be implanted into an existing tissue and readily perfused
Solution Approach 1:
The bioreactor system dynamically changes key parameters including flow rate, shear stress, and biochemical concentration gradients during the vascularization process. By progressively adjusting these parameters to mimic in vivo conditions, the system guides the development of microvessel networks with appropriate structural organization, maturity, and functional characteristics for successful implantation and integration into host tissue.
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 bioreactor system effectively promotes the formation of a dense and functional vascular network within tissue constructs, enhancing their viability and ability to perfuse nutrients and oxygen, addressing the limitations of existing methods by maintaining vessel maturity and density.
Implementation Method 1
The upper and lower biochambers are then perfused with a cell culture media for a predetermined time period such that the tissue construct is indirectly perfused and undergoes vascularization
Data Source
AI summary
A modular bioreactor is provided that includes an upper biochamber; a lower biochamber; and an intermediate biochamber that is positioned between the upper biochamber and the lower biochamber. Each biochamber of the bioreactor is in fluid communication with each other biochamber of the bioreactor and includes an interior wall, which defines a centrally-disposed cavity for each biochamber, and an inflow port and an outflow port that are in fluid communication with each centrally disposed cavity. Systems and methods for vascularizing a tissue construct are also provided.