Shear-Thinning Hydrogels with Stimulus-Triggered Covalent Crosslinking
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Solution Overview
Problem
Current shear-thinning hydrogel systems suffer from instability due to bio-erosion, where the gel structures break down over time due to the longer-term instability of non-covalent crosslinking, leading to premature degradation and loss of functionality in clinical applications.
Innovation Solution
Development of settable, shear-thinning hydrogels with non-covalent crosslinks that can undergo chemical covalent cross-linking reactions, either spontaneously or upon stimulus, to stabilize the hydrogel network, enhancing mechanical stability and resistance to bio-erosion.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If non-covalent crosslinks are used in shear-thinning hydrogels to enable injectability and shear-thinning behavior, then the hydrogels can be delivered via minimally invasive methods, but the hydrogels suffer from bio-erosion and structural instability over time
Solution Approach 1:
The patent applies preliminary action by incorporating latent covalent crosslinking moieties into the hydrogel network before delivery. These moieties remain dormant during injection but are activated after implantation to form stable covalent crosslinks, thereby preventing bio-erosion while maintaining injectability. This is achieved through pre-functionalization of polymer chains with reactive groups that can undergo crosslinking reactions upon exposure to physiological conditions or external stimuli.
Solution Approach 2:
The patent implements dynamics by creating a time-dependent evolution of the hydrogel structure. Initially, the hydrogel relies on reversible non-covalent crosslinks that allow shear-thinning and injection. Over time, these dynamic bonds are replaced by stable covalent crosslinks through in situ crosslinking reactions. This dynamic transition from non-covalent to covalent networking resolves the contradiction between initial injectability and long-term stability.
2Speed
If non-covalent crosslinking is used to achieve shear-thinning properties, then the hydrogel can flow under shear stress for injection, but the gel structures break down with time due to instability
Solution Approach 1:
The patent applies parameter changes by utilizing the time-dependent transformation of crosslinking strength. The hydrogel system transitions from weak non-covalent interactions (allowing flow) to strong covalent bonds (preventing breakdown). This parameter change in bond strength over time enables the material to exhibit both rapid flow under shear during injection and prolonged structural integrity during sustained release, resolving the contradiction between speed of delivery and duration of functionality.
3Strength
If the hydrogel structure is stabilized with covalent crosslinks, then mechanical stability is improved, but the ability to undergo shear-thinning and injection is reduced
Solution Approach 1:
The patent applies segmentation by separating the crosslinking function into two distinct phases: (1) temporary non-covalent crosslinks that provide shear-thinning during injection, and (2) permanent covalent crosslinks that provide mechanical stability after implantation. This segmentation of crosslinking mechanisms allows the hydrogel to exhibit appropriate rheological properties at different stages of its lifecycle, resolving the contradiction between injectability and mechanical strength.
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 hydrogels exhibit improved mechanical stability, reduced bio-erosion, and controlled release of therapeutic agents, maintaining structural integrity and functionality for extended periods, suitable for biomedical applications such as drug delivery and tissue engineering.
Implementation Method 1
at least one set of chemical moieties being capable of participating in at least one chemical covalent cross-linking reaction
Implementation Method 2
shear-thinning hydrogels, each hydrogel comprising a hydrophilic polymer network, said hydrophilic polymer network comprising non-covalent crosslinks
Data Source
AI summary
The present inventions are directed to shear-thinning and stabilizing hydrogels, especially for use in drug delivery and therapy. Various embodiments provide settable, shear-thinning hydrogels, each hydrogel comprising a hydrophilic polymer network, said hydrophilic polymer network comprising non-covalent crosslinks and at least one set of chemical moieties being capable of participating in at least one chemical covalent cross-linking reaction. In certain embodiments, these settable shear-thinning hydrogels are triggerable to cross-link by the application of a stimulus.