3D-Printed Evacuable Scaffolds for Perfusion Tissue Constructs
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current drug screening and disease studies using animal models often yield inconsistent results due to their inability to accurately represent human equivalents, and existing three-dimensional tissue models are limited by diffusion constraints and nutritional requirements, making them poorly suited for co-culture.
Innovation Solution
A printed tissue construct comprising living cells or tissue fragments encapsulated in a hydrogel-based extracellular matrix substitute with hollow lumens, allowing for perfusion with specific growth media and mimicking in vivo vasculature, constructed using methods such as 3D-printed poly-vinyl alcohol or alginate-pluronic structures that are dissolvable in aqueous solvents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If three-dimensional tissue models are constructed to improve biological complexity representation, then the accuracy of human disease modeling is improved, but diffusion limitations of nutrients and cell viability are worsened due to increased structural size
Solution Approach 1:
The tissue construct is divided into multiple segments by incorporating a three-dimensional network of hollow channels (lumens) throughout the hydrogel matrix. These channels segment the tissue into smaller regions that are closer to nutrient sources, ensuring that no cell is more than a certain distance from perfusion. This segmentation resolves the contradiction by maintaining small effective diffusion distances while allowing the overall construct to achieve large size for biological complexity.
Solution Approach 2:
A perfusion system acts as an intermediary to deliver nutrients and remove waste products through the hollow channels embedded in the hydrogel matrix. This intermediary perfusion network resolves the diffusion limitation problem by providing an active transport mechanism that bypasses the passive diffusion constraints of solid tissue, thereby maintaining cell viability in large-scale three-dimensional constructs.
2Reliability
If vascularized three-dimensional tissue models are constructed to overcome diffusion limitations, then nutrient delivery is improved, but the complexity of construction and perfusion system integration is worsened
Solution Approach 1:
The hollow channels are pre-formed within the hydrogel matrix before cell seeding and tissue construction. The three-dimensional network of lumens is established in advance as part of the scaffold architecture, eliminating the need for complex post-construct vascularization procedures. This preliminary action resolves the contradiction by simplifying the overall construction process while ensuring reliable nutrient delivery pathways are already in place.
Solution Approach 2:
The hydrogel material properties are modified to enable seamless integration of the perfusion system. The hydrogel's porosity, permeability, and mechanical properties are tuned to allow easy incorporation of hollow channels and facilitate perfusion flow. This parameter change resolves the contradiction by making the construction process more straightforward while maintaining reliable nutrient delivery through the modified material properties.
3Productivity
If large-scale tissue constructs are created to improve scalability, then model scalability is improved, but diffusion constraints and cell survival are worsened
Solution Approach 1:
The large-scale tissue construct is segmented into multiple smaller functional units by the three-dimensional network of hollow channels. Each segment or region is closely connected to the perfusion system through this channel network, ensuring that even in large-scale constructs, no cell is far from nutrient supply. This segmentation allows scalability to be achieved while maintaining cell survival rates.
Solution Approach 2:
A hydraulic perfusion system is implemented to actively pump nutrients and fluids through the hollow channels embedded in the hydrogel matrix. This hydraulic system overcomes the passive diffusion limitations that would normally constrain large-scale tissue construction. By introducing active fluid flow, the system enables large-scale scalability while maintaining cell survival through continuous nutrient delivery and waste removal.
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 creates a more accurate and scalable in vitro model that overcomes diffusion limitations, enabling sustained growth and perfusion of cells and tissues, mimicking in vivo conditions and facilitating the study of human diseases.
Implementation Method 1
The free-standing filament structure is dissolved and removed from the hydrogel after the hydrogel is gelated to a solid phase
Implementation Method 2
the hydrogel can include at least one lumen created by loading a free-standing evacuable filament structure in the hydrogel while the hydrogel is in a liquid phase
Implementation Method 3
The hollow channels may or may not be lined with endothelial cells or epithelial cells of various types in order to better mimic in vivo vasculature or other organ constructs
Data Source
AI summary
The present disclosure provides information on the methodology used in the fabrication of three-dimensional cellularized tissue constructs from free-standing evacuable 3D printed composites and/or scaffolds embedded in an extracellular matrix mimic generated from biocompatible materials. The purposes of using these composite and/or scaffold materials is to generate complex embedded lumens that allow for complete perfusion of the matrix construct by standard cell culture media, thereby allowing for maintenance of large-scale 3D cell cultures in specific geometric forms. The use of biological extracellular matrix materials is to provide essential biological and mechanical signals needed to regulate the behavior of encapsulated cells. Furthermore, the methodology can be adapted such that the lumens generated are capable of being seeded with various endothelial and epithelial cell types as desired, thereby allowing for mimicry of in vivo vasculature, intestinal tracts, and other lumen-containing constructs. This disclosure provides the methodology for generating the tissue constructs.