Bioactive Granular Hydrogel Scaffolds with Light-Free Assembly
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Conventional hydrogel scaffolds made from gelatin methacryloyl (GelMA) are thermally unstable and dissolve at physiological temperatures, limiting their use in tissue engineering and 3D bioprinting applications that require stability and assembly within tissues without light exposure.
Innovation Solution
The formation of hydrogel microparticles (HMP) is achieved through chemical crosslinking followed by non-light-mediated assembly using enzymatic activation, such as Factor XIII-mediated glutamyl-lysine bond formation, allowing for the creation of stable granular hydrogel scaffolds (GHS) that can mimic tissue physiochemical and biological characteristics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If GelMA hydrogel microparticles are physically crosslinked by lowering temperature below sol-gel temperature, then the microparticles can be formed and packed, but they dissolve at physiological temperature and cannot form stable granular hydrogel scaffolds
Solution Approach 1:
The patent applies preliminary action by performing chemical crosslinking of GelMA microparticles at low temperature (4°C) using EDC/NHS chemistry before they are subjected to physiological conditions. This pre-crosslinking creates stable covalent bonds that prevent dissolution at physiological temperature, allowing the microparticles to maintain their structural integrity when formed into granular hydrogel scaffolds.
Solution Approach 2:
The patent changes the chemical parameters of the GelMA system by introducing carbodiimide crosslinking chemistry (EDC/NHS) that creates stable amide bonds between carboxyl and amine groups. This chemical modification transforms the physically crosslinked, thermally unstable microparticles into chemically crosslinked, thermally stable structures that can form stable granular hydrogel scaffolds at physiological temperature.
2Reliability
If conventional GelMA scaffolds are used, then tissue engineering applications can be performed, but light exposure is required for scaffold formation which limits noninvasive application
Solution Approach 1:
The patent replaces the light-based photopolymerization system with a chemical crosslinking system using EDC/NHS chemistry. This substitution eliminates the requirement for light exposure during scaffold formation, enabling noninvasive injection and in situ formation of granular hydrogel scaffolds within tissues without the need for surgical access or light delivery systems.
Solution Approach 2:
The patent introduces EDC (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide) and NHS (N-hydroxysuccinimide) as chemical intermediaries that mediate the crosslinking reaction between GelMA microparticles. These intermediaries enable covalent bond formation without requiring light activation, allowing the scaffold formation process to occur in the dark within the body through simple injection and chemical reaction.
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 enables the formation of stable hydrogel scaffolds that can be injected into tissues without light access, facilitating noninvasive or minimally invasive tissue regeneration, vascularization, and tissue function improvement, with enhanced bioactivity through encapsulation of biologics and colloidal particles.
Implementation Method 1
A polymer can first be converted to stable microgels (micro-scale hydrogel particles) via chemical crosslinking
Implementation Method 2
followed by non-light-mediated assembly using enzymatic activation, such as Factor XIII-mediated glutamyl-lysine bond formation
Data Source
AI summary
Embodiments relate to a method of forming a granular hydrogel scaffold (GHS). The method comprises converting polymers to form hydrogel microparticles (HMP) via a first crosslinking and assembling the HMP to form GHS via non-light-mediated crosslinking with or without coating or embedding them with any biologies or nanoparticles.