Dual-crosslinked Hydrogel for Tissue Engineering
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Solution Overview
Problem
Current injectable hydrogel systems for tissue engineering face limitations such as low mechanical strength, rapid degradation, and lack of self-healing capabilities, which restrict their applications due to premature crosslinking and undesirable material properties.
Innovation Solution
A dual-crosslinked hydrogel system is developed using hyaluronic acid functionalized with methacrylate and hydrazide groups, and dextran oxidized to aldehyde groups, allowing for gentle dynamic covalent acylhydrazone bond crosslinking followed by secondary photopolymerization for enhanced mechanical properties and cytocompatibility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If single covalent bonding crosslinking is used, then mechanical strength is improved, but self-healing capability is lost
Solution Approach 1:
The patent combines two crosslinking mechanisms: dynamic reversible crosslinking (for self-healing) and covalent bonding crosslinking (for mechanical strength). The dynamic crosslinks between hyaluronic acid and dextran provide reversibility for self-healing, while the covalent bonds between methacrylate groups provide structural stability and strength.
Solution Approach 2:
The hydrogel forms a composite network structure incorporating both dynamic reversible bonds and permanent covalent bonds. This composite crosslinking system allows the material to exhibit both self-healing properties (from dynamic bonds) and enhanced mechanical strength (from covalent bonds).
2Speed
If fast crosslinking reaction is used, then gelation speed is improved, but premature crosslinking occurs
Solution Approach 1:
The hydrogel components are pre-functionalized with reactive groups (methacrylate, hydrazide, aldehyde) during synthesis, but the actual crosslinking reaction is triggered only after injection through physiological conditions or mild stimulation. This preliminary preparation allows fast gelation when needed while preventing premature reaction during storage and delivery.
Solution Approach 2:
The crosslinking reaction kinetics are controlled by adjusting parameters such as pH, temperature, and presence of catalysts. The reaction proceeds slowly under storage conditions but accelerates upon injection through changes in these parameters, achieving fast gelation without premature crosslinking.
3Strength
If high mechanical strength is achieved, then structural stability is improved, but material complexity increases
Solution Approach 1:
Different regions of the hydrogel network have different crosslinking densities and bond types. The dynamic crosslinks provide local flexibility and self-healing, while covalent crosslinks provide local structural stability. This spatial differentiation of bond characteristics achieves overall structural stability without requiring uniform complexity throughout the material.
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 dual-crosslinked hydrogel exhibits improved mechanical strength with storage moduli up to 1000 kPa, slow mass loss, and high cell viability, making it suitable for tissue engineering applications like cartilage regeneration.
Implementation Method 1
a secondary covalent crosslinking occurs in situ via photopolymerization of methacrylate functional groups
Implementation Method 2
crosslinking the methacrylate and hydrazide group functionalized glycosaminoglycan and the second-polysaccharide-aldehyde to form a dynamic acylhydrazone bond cross-linked hydrogel
Data Source
Figure 1(a)~1(b)
Figure 1(c)~1(d)
Figure 2(a)~2(b)
AI summary
A process to prepare a dual-crosslinked hydrogel, comprising the following steps: 1) functionalizing a glycosaminoglycan such as hyaluronic acid with a methacrylate on hydroxyl group and with a dihydrazide on carboxyl group to obtain a methacrylate and hydrazide group functionalized glycosaminoglycan, wherein the degree of methacrylation is 5-200%, and the degree of hydrazide group modification is 8-70%; oxidizing a second-polysaccharide such as dextran to obtain a second-polysaccharide with aldehyde groups, the degree of aldehyde modification in the second-polysaccharide is 10-95%; 2) crosslinking the methacrylate and hydrazide group functionalized glycosaminoglycan and the second-polysaccharide-aldehyde in an aqueous solvent, to form a dynamic acylhydrazone bond cross-linked hydrogel; and 3) photopolymerizing the dynamic acylhydrazone bond cross-linked hydrogel by irradiation under the presence of a photoinitiator. The dual-crosslinked hydrogel prepared according to the process, a hydrogel precursor to prepare a dual-crosslinked hydrogel, and use thereof are also provided.