Reinforced Cellularized Tissue Using Biocompatible Hydrogel Crosslinking
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Solution Overview
Problem
Existing 3D bioprinting technologies face challenges in creating mechanically robust, thick, vascularized cardiac tissues due to the inferior mechanical properties of natural ECM-based biomaterials, which disintegrate under stress, and cross-linking methods like UV exposure or genipin are harmful or difficult to control.
Innovation Solution
A method involving a biocompatible small-molecule reinforcing agent, such as oxidized sucrose (SOx), is used to chemically interact with ECM-based hydrogels post-assembly, increasing the compressive modulus by at least 10% while maintaining cell viability, allowing for homogeneous reinforcement of engineered cellularized constructs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ECM-based hydrogels are used as scaffold material in tissue engineering, then cell adhesion and maturation are improved, but mechanical strength deteriorates
Solution Approach 1:
The patent combines natural ECM-based hydrogels with synthetic crosslinking agents to create a composite material system. The hydrogel provides biocompatibility and cell adhesion while the synthetic crosslinking agent provides mechanical strength, resolving the contradiction between biological functionality and mechanical robustness.
Solution Approach 2:
The patent modifies the chemical parameters of the ECM hydrogel by introducing crosslinking agents that change the material's mechanical properties. This chemical modification increases the compressive modulus and tensile strength while maintaining the hydrogel's biological functionality through controlled crosslinking density.
2Strength
If cross-linking methods like UV exposure or genipin are used to strengthen ECM hydrogels, then mechanical strength is improved, but cell viability deteriorates
Solution Approach 1:
The patent introduces a crosslinking agent that acts as an intermediary between the ECM hydrogel and the crosslinking process. This mediator enables crosslinking to occur under mild conditions that preserve cell viability, avoiding the harmful effects of direct UV exposure or genipin treatment.
Solution Approach 2:
The patent replaces harsh physical crosslinking methods (UV radiation) with chemical crosslinking mechanisms that occur under physiological conditions. This substitution eliminates the need for high-energy radiation that would damage cells while still achieving the desired mechanical reinforcement.
3Adaptability or versatility
If thick vascularized cardiac tissues are fabricated by 3D bioprinting, then tissue functionality is improved, but mechanical robustness deteriorates
Solution Approach 1:
The patent applies crosslinking treatment as a preliminary action after 3D bioprinting the thick vascularized cardiac tissue. This post-fabrication reinforcement step strengthens the mechanically vulnerable printed structure before implantation, enabling it to withstand physiological stresses while maintaining its complex vascular architecture.
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 method enhances the mechanical strength of 3D bioprinted tissues, ensuring they withstand stress without deformation, making them suitable for transplantation and minimally invasive procedures.
Implementation Method 1
contacting the engineered cellularized construct with a biocompatible small-molecule reinforcing agent that is capable of chemically interacting with the ECM-based hydrogel... to thereby increase a compressive modulus of the ECM-based hydrogel
Data Source
AI summary
A method for generating reinforced engineered cellularized construct, which utilizes a biocompatible small-molecule reinforcing agent that do not affect the viability of the cells, a reinforced engineered cellularized construct obtained thereby and used the engineered cellularized construct are provided.