Scaffold-Free Multilayer Vascular Tubes via Bioprinting
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Solution Overview
Problem
There is a need for replacement blood vessels for small diameter arteries and abdominal organs, particularly for diameters less than six millimeters, as existing artificial materials face high rates of thrombosis, and current tissue-engineered vascular grafts lack compliance and cannot withstand physiological blood pressures without synthetic scaffolds.
Innovation Solution
Engineered multilayer vascular tubes are created using a bioprinter with layers of differentiated adult fibroblasts, smooth muscle cells, and endothelial cells, with a specific ratio of endothelial to smooth muscle cells (5:95 to 45:55) and without pre-formed scaffolds, ensuring compliance and ability to withstand physiological pressures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If pre-formed scaffolds are used in tissue-engineered vascular grafts, then structural support is provided, but compliance and ability to withstand physiological blood pressures are compromised
Solution Approach 1:
The invention removes pre-formed scaffolds from the tissue-engineered vascular graft construction process. Instead of using synthetic or decellularized matrix scaffolds as templates, the method relies on self-assembly of living cells into functional vascular structures through bioprinting and in situ organization, thereby eliminating the compliance limitations imposed by scaffold materials.
Solution Approach 2:
The invention enables living cells to self-organize and self-assemble into functional vascular structures without requiring pre-formed scaffolds. The bioprinted cell layers spontaneously differentiate and organize into mature vascular tissue with proper compliance characteristics, allowing the tissue to serve itself in creating the necessary structural properties.
2Ease of manufacture
If artificial materials are used for small diameter arteries, then replacement is possible, but high rates of thrombosis occur
Solution Approach 1:
The invention creates a composite living tissue structure composed of multiple cell types (endothelial cells, smooth muscle cells, fibroblasts) organized in physiologically relevant layers. This living composite material replaces inert artificial materials, providing both manufacturability for small diameter vessels and thrombosis resistance through the natural anticoagulant properties of the endothelial cell layer.
Solution Approach 2:
The invention changes the fundamental parameter of graft material from inert synthetic polymer to living biological tissue. This parameter change transforms the surface properties and hemocompatibility characteristics, eliminating the thrombogenic response associated with artificial materials while maintaining the ability to manufacture small diameter grafts.
3Adaptability or versatility
If bioprinting is used to create multilayer vascular tubes, then scaffold-free construction is achieved, but manufacturing complexity increases
Solution Approach 1:
The invention segments the vascular wall into distinct cell layers (intima, media, adventitia) and prints each layer separately using bioprinting technology. This segmentation approach enables scaffold-free construction of complex multilayer structures while managing manufacturing complexity through systematic layer-by-layer fabrication rather than attempting to create the entire structure simultaneously.
Solution Approach 2:
The invention transitions from two-dimensional cell culture to three-dimensional vascular structure fabrication using bioprinting. By adding the vertical dimension through layered deposition, the method achieves scaffold-free construction of tubular structures with proper wall thickness and lumen formation, managing complexity through spatial organization rather than procedural complexity.
Data Source
AI summary
Described herein are engineered multilayered vascular tubes comprising at least one layer of differentiated adult fibroblasts, at least one layer of differentiated adult smooth muscle cells, wherein any layer further comprises differentiated adult endothelial cells, wherein said tubes have the following features: (a) a ratio of endothelial cells to smooth muscle cells of about 1 : 99 to about 45:55; (b) the tube is compliant; (c) the internal diameter of the tube is about 6 mm or smaller; (d) the length of the tube is up to about 30 cm; and (e) the thickness of the tube is substantially uniform along a region of the tube; provided that the engineered multilayered vascular tube is free of any pre-formed scaffold. Also described herein are methods of forming said tubes and uses for said tubes including methods for treating patients, comprising providing such a tube into to a patient in need thereof.