3D Perfusable Network Fabrication With Tunable Vascular Diameters
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Solution Overview
Problem
The challenge in fabricating three-dimensional (3D) multicellular structures, particularly perfusable vascular networks, lies in the lack of technology to create multi-scale, branched structures with specified geometry and varying luminal diameters, essential for tissue engineering and in vitro models, due to limitations in oxygen and nutrient diffusion.
Innovation Solution
The method employs crosslinkable polymers and gelling agents in support materials, combined with sacrificial inks and crosslinking initiators, to form 3D perfusable networks through 3D bioprinting, allowing for the fabrication of complex networks with seamless junctions and tunable inner and outer diameters, using photocrosslinking, small molecule, or enzymatic crosslinking mechanisms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Shape
If traditional 3D bioprinting methods are used to fabricate vascular networks, then basic structural formation is achieved, but the ability to create complex multi-scale branched structures with varying diameters and seamless junctions is insufficient
Solution Approach 1:
The fabrication process is divided into two distinct stages: first printing the sacrificial ink structure with the desired complex geometry, then removing the sacrificial material to create the final perfusable network. This segmentation allows independent optimization of printing ease and geometric precision.
Solution Approach 2:
A sacrificial ink composed of gelatin microgels is used as an intermediary material that can be easily printed with complex geometries and then completely removed to leave behind precise hollow channels. The sacrificial material enables seamless junctions by filling entire volumetric regions including branch points.
Solution Approach 3:
The physical state of the sacrificial ink is changed from solid (at printing temperature) to liquid/dissolved (after heating to 37°C), enabling complete removal and creation of perfusable channels. This parameter change allows transition from structural support to material removal.
2Reliability
If sacrificial ink is used to create hollow channels, then perfusable networks are formed, but the structural support during printing is insufficient
Solution Approach 1:
The hydrogel matrix provides localized structural support exactly where needed during printing, while the sacrificial ink maintains its own microgel structure for geometric fidelity. Each material performs its specific function locally without interfering with the other's properties.
Solution Approach 2:
The system uses a composite approach with hydrogel matrix providing macroscopic structural support and gelatin microgels providing microscopic geometric definition. The combination of these two materials enables both structural integrity during printing and precise channel geometry after processing.
3Adaptability or versatility
If existing bioprinting methods are used, then simple structures can be fabricated, but the ability to independently tune inner and outer diameters of channels is limited
Solution Approach 1:
The system enables dynamic control of channel dimensions by varying printing parameters such as nozzle diameter, printing speed, and ink flow rate. The inner diameter is controlled by the printed sacrificial ink filament width, while the outer diameter is controlled by the diffusion distance of crosslinking agents, allowing independent tuning of both dimensions.
Solution Approach 2:
Different physical and chemical parameters can be adjusted to control vessel dimensions: temperature affects microgel packing and filament diameter, crosslinking agent concentration and diffusion time control outer diameter, and printing speed affects inner diameter. This multi-parameter control enables versatile dimension tuning.
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 perfusable networks with controlled channel diameters and branch points, facilitating the transport of fluids or gases, and supports the integration of endothelial and smooth muscle cell structures, enhancing the viability and functionality of 3D bioprinted tissues.
Implementation Method 1
Injecting the printable composition into the support material allows for the diffusion of the crosslinking initiator from the printable composition into the support material
Implementation Method 2
Melting the sacrificial ink in the printable composition encased in the crosslinked polymers, generates 3D hollow (i.e. perfusable) networks
Implementation Method 3
a sacrificial ink comprising gelatin microgels is melted by raising the temperature of the support material to at least about 25° C., at least about 30° C., at least about 33° C., and up to about 37° C.
Implementation Method 4
a sacrificial ink comprising a poloxamer polymer, e.g. Pluronic F-127, is melted by lowering the temperature of the support material to less than about 10° C., less than about 5° C., and down to about 0° C.
Implementation Method 5
exposing the support material to ultraviolet irradiation
Data Source
AI summary
Methods and compositions for fabricating 3D perfusable networks are described. The methods utilize (1) printable compositions comprising gelatin microgels or Pluronic F-127, and crosslinking initiators; and (2) support materials comprising crosslinkable polymers and gelling agents. In some embodiments, the support material further comprises a co-initiator.