Injectable Macroporous Hydrogels via Phase Separation
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Solution Overview
Problem
Current methods for producing injectable, tissue-compatible macroporous hydrogels for regenerative medicine are limited by harsh processing conditions, non-injectable formulations, slow pore formation, and limited control over pore sizes, which hinder their use in clinical applications.
Innovation Solution
A method involving an aqueous solution of cross-linkable polyethylene glycol (PEG) derivatives and polysaccharide kosmotropic agents, such as hyaluronan, with a cross-linking reagent to initiate gelation and phase-separation, allowing for the formation of injectable, macroporous hydrogels with tunable pore sizes and improved biocompatibility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Shape
If established methods (salt leaching, freeze drying, gas pocket formation) are used to form macroporous hydrogels, then macroporous structure is achieved, but the process requires prior material templating in harsh conditions and is not injectable
Solution Approach 1:
The patent utilizes phase separation between two aqueous phases (PEG-rich and polysaccharide-rich) that occurs during gelation to create macropores. The phase transition from homogeneous solution to separated phases generates the porous structure without requiring harsh templating conditions, making the hydrogel injectable while maintaining macroporosity
Solution Approach 2:
The system self-assembles into macroporous structure through spontaneous phase separation during cross-linking. The PEG and polysaccharide components automatically separate into distinct phases, with the PEG forming the gel matrix and polysaccharide creating pores, eliminating the need for external templating or complex processing steps
2Ease of operation
If microparticle fusion or sacrificial porogen inclusion methods are used, then cell-compatible injectable hydrogels are produced, but preprocessing is heavy or pore formation is slow
Solution Approach 1:
The patent combines gelation and phase separation into a single simultaneous process. The cross-linking of PEG triggers phase separation between PEG-rich and polysaccharide-rich phases, creating macropores during gel formation rather than requiring separate preprocessing steps or slow degradation processes
Solution Approach 2:
The rapid phase separation that occurs during gelation enables fast pore formation. The system transitions from a homogeneous aqueous solution to separated phases within minutes, creating the porous structure quickly without requiring heavy preprocessing or slow porogen degradation
3Shape
If two-phase systems are used to produce porous gels, then pore structure is formed, but the conditions are not compatible with injectability and cell encapsulation
Solution Approach 1:
The patent optimizes the composition and concentration parameters of the aqueous phases to achieve phase separation under physiological conditions. By adjusting PEG and polysaccharide concentrations and molecular weights, the system forms macropores while maintaining isotonicity and biocompatibility, enabling injectability and cell encapsulation
Solution Approach 2:
The hydrogel combines PEG (forming the gel matrix) with polysaccharides (forming pores) to create a composite macroporous structure. This composite system maintains the benefits of both components: PEG provides gelation and structural integrity, while polysaccharides create porosity and facilitate transport, all under cell-compatible conditions
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 creation of biocompatible, injectable macroporous hydrogels with controlled pore sizes, enhanced stability, and compatibility for cell encapsulation, facilitating tissue regeneration and neural network formation with improved neurite outgrowth and stability.
Implementation Method 1
adding to this mixture a cross-linking reagent able to cross-link said cross-linkable derivative of a PEG, thus simultaneously initiating gelation of the cross-linkable derivative of a PEG
Implementation Method 2
adding to this mixture a cross-linking reagent able to cross-link said cross-linkable derivative of a PEG, thus simultaneously initiating gelation of the cross-linkable derivative of a PEG and phase-separation
Data Source
Figure 1a~2d
Figure 3a~4d
Figure 5a~5c
AI summary
The invention relates to a method for providing a macroporous hydrogel, comprising the steps of a) providing an aqueous solution comprising a cross-linkable derivative of a polyethylene glycol (PEG) and a polysaccharide kosmotropic agent, and b) adding a crosslinking reagent able to cross-link said cross-linkable derivative of a PEG, thus simultaneously initiating gelation and phase-separation.