Sacrificial Fiber Vascular Network Preform Fabrication
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Solution Overview
Problem
Current tissue engineering techniques face challenges in creating vascularized constructs that can be scaled up beyond a few millimeters in size, as they lack a functional microvascular network, restricting the size and thickness of artificial tissue implants due to limited nutrient diffusion, and require host vessel ingrowth for vascularization, which is slow and unreliable.
Innovation Solution
A method involving the use of sacrificial water-soluble sugar fiber structures to create a 3D vascular network preform with scalable, customizable channels that mimic native capillaries and arterioles, allowing for the formation of larger vascularized constructs that can be anastomosed directly to the host vasculature, using a matrix that is poured over the fiber network and then dissolved to create channels of varying diameters.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Volume of moving object
If tissue constructs are made larger than a few millimeters in size, then the construct can provide more functional tissue, but the construct cannot survive due to limited nutrient diffusion from host vessels
Solution Approach 1:
The patent applies preliminary action by pre-forming a functional microvascular network within the tissue construct before implantation. sacrificial fibers are embedded in the matrix to create channels that will become blood vessels, allowing the construct to be self-sufficient from the start rather than relying on slow host vessel ingrowth after implantation
Solution Approach 2:
The patent uses sacrificial fibers as an intermediary structure to create the vascular network. These water-soluble fibers are temporarily embedded in the tissue matrix, then dissolved to leave behind hollow channels that are subsequently perfused with endothelial cells to form functional blood vessels
2Reliability
If a de novo microvascular network is created, then the network can supply oxygen and nutrients to deeper portions, but the network remains microscopic and cannot be anastomosed to host vasculature
Solution Approach 1:
The patent applies segmentation by creating a hierarchical vascular network with different scale levels. The sacrificial fiber network creates a segmented structure of interconnected channels that can be perfused with cells to form a complete microvascular system, while larger caliber vessels are created separately for anastomosis to host vasculature
3Ease of manufacture
If host vessel ingrowth is used for vascularization, then the process is simple, but the pace is slow and the reliability is low
Solution Approach 1:
The patent applies self-service by providing the tissue construct with its own pre-formed vascular network that can immediately perfuse itself with oxygen and nutrients upon implantation. The construct does not need to wait for host vessels to grow into it, as the sacrificial fiber channels are already in place to support immediate cellular perfusion
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 vascularized constructs that can be immediately perfused and survive beyond several millimeters in size, overcoming the limitations of diffusion-limited growth and providing a rapid, inexpensive method for fabricating tissue scaffolds with integrated vascular networks.
Implementation Method 1
A method involving the use of sacrificial water-soluble sugar fiber structures to create a 3D vascular network preform with scalable, customizable channels that mimic native capillaries and arterioles, allowing for the formation of larger vascularized constructs that can be anastomosed directly to the host vasculature, using a matrix that is poured over the fiber network and then dissolved to create channels of varying diameters.
Data Source
AI summary
The first aspect of the present invention is directed to a method of producing a vascular network preform (VNP). This method involves forming a network of elongate fibers and at least one elongate structure from a sacrificial material. The diameter of the elongate structure is greater than that of the elongate fibers. The network of elongate fibers is placed in contact with at least one elongate structure either following or during forming the network of elongate fibers or forming the at least one elongate structure. A matrix is applied around the network of elongate fibers, in contact with the at least one elongate structure. The network of elongate fibers and elongate structure, within the matrix is sacrificed to form a preform. The resulting preform contains a vascular network of fine diameter tubes in contact with at least one elongate passage having a diameter greater than that of the fine diameter tubes. The resulting solid preform and methods of using it are also disclosed.