DNA-Modified Hydrogel for Dynamic 3D Cell Culture
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Solution Overview
Problem
Existing three-dimensional cell culture matrices, particularly those based on Matrigel, lack the ability to dynamically adjust composition, porosity, and mechanical properties, leading to restricted applications in regenerative medicine and batch-to-batch variations.
Innovation Solution
A hydrogel material with main chain polymers modified with anchor modules in the form of functionalized DNA single strands, allowing for crosslinking through intermolecular DNA double strand formation, which can be dynamically controlled by adding further DNA components and using temperature-dependent DNA blocking strands.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If biologically created cell culture matrices (Matrigel) are used, then organoid structures can be produced, but the material properties cannot be adapted or changed and batch-to-batch variations occur
Solution Approach 1:
The patent applies parameter changes by using DNA sequence design to precisely control hydrogel properties. By modifying DNA sequences (particularly the number of N-bases and base combinations at specific positions), the invention enables systematic adjustment of crosslinking strength, mechanical properties, and degradation rates, thereby achieving adaptability while maintaining compositional consistency across batches.
Solution Approach 2:
The invention creates a composite material system combining synthetic polymers with functionalized DNA molecules. This composite approach allows the hydrogel to integrate the structural stability of synthetic polymers with the programmable, adaptive properties of DNA, resolving the contradiction between adaptability and compositional stability.
2Ease of manufacture
If Matrigel is used for organoid production, then cell culture matrices are available, but undesirable components cannot be easily removed and regenerative medicine applications are restricted
Solution Approach 1:
The patent extracts and eliminates the problematic biological components from Matrigel by replacing them with fully synthetic polymer-DNA composite materials. This extraction of undesirable components while retaining the essential hydrogel functionality enables easier manufacturing and removes restrictions for regenerative medicine applications.
Solution Approach 2:
The invention employs synthetic, programmable DNA components that can be precisely controlled and discarded after use, replacing the complex, hard-to-purify biological materials. This approach simplifies manufacturing processes and eliminates concerns about residual undesirable components.
3Reliability
If three-dimensional cell culture matrices are used, then cell growth is better simulated, but the composition and mechanical properties cannot be dynamically changed
Solution Approach 1:
The patent implements dynamics by incorporating temperature-responsive DNA blocking strands that can be reversibly activated. By changing temperature, the blocking strands undergo conformational changes that dynamically adjust DNA crosslinking, thereby enabling real-time modification of hydrogel mechanical properties and composition while maintaining reliable physiological simulation.
Solution Approach 2:
The invention utilizes phase transitions of DNA blocking strands in response to temperature changes. These phase transitions enable the hydrogel to dynamically switch between different structural states, allowing composition and mechanical property adjustments without compromising the physiological environment simulation.
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 hydrogel material can adapt its properties to meet the needs of cells, providing a customizable matrix for 3D cell cultures and organoid structures with improved mechanical strength, homogeneity, and reduced batch variations, suitable for regenerative medicine applications.
Implementation Method 1
the main chain polymers can be crosslinked with one another by intermolecular DNA double strand formation
Implementation Method 2
a DNA sequence of the anchor modules... is blocked by a temperature-dependent DNA blocking strand
Data Source
AI summary
A modifiable hydrogel material has main chain polymers which are modified with anchor modules in the form of predetermined functionalized single strands of DNA. The main chain polymers can be crosslinked with one another by intermolecular DNA double strand formation. A DNA sequence of the anchor modules has a predetermined number of specific sequence positions N with different base combinations and/or is blocked by a temperature-dependent DNA blocking strand. In a method for producing a hydrogel with the modifiable hydrogel material, DNA modules in the form of free DNA single strands or DNA modules in the form of predetermined DNA single strand pairs which bind to anchor modules in a complementary manner are employed for crosslinking the main chain polymers, which form an intermolecular DNA double strand at a common binding domain.