Extracellular Matrix Hydrogel Formation Without ECM Protein Damage
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Solution Overview
Problem
Current hydrogel systems used as ECM models do not accurately replicate the structure, physicochemical properties, and biocompatibility of human extracellular matrices, as they either lack native proteins or destroy them, leading to unnatural protein compositions and lack of complexity.
Innovation Solution
A method for producing an extracellular matrix hydrogel involves decellularizing a tissue sample, depolymerizing it with a chaotropic agent and surfactant, and gelling the resulting sol to form a hydrogel that retains intact primary and secondary protein structures, which is then sterilized and modulated for stiffness using a hygroscopic agent.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional hydrogel systems (EHS mouse basement membrane extracts, synthetic polymers, or pepsin-digested human-derived hydrogels) are used to mimic natural tissue scaffolds, then the hydrogels can be produced with varying degrees of structural organization, but they either do not include initial extracellular matrix proteins, destroy the proteins, or have altered primary structure of ECM proteins
Solution Approach 1:
The patent extracts and isolates intact ECM proteins from tissue samples through a specialized process that removes cellular components while preserving the extracellular matrix proteins in their native state, avoiding the protein degradation that occurs in traditional pepsin-digested methods
Solution Approach 2:
The patent changes the processing parameters by using mild extraction conditions, specific enzyme treatments, and controlled pH levels to preserve the primary structure of ECM proteins while still achieving effective decellularization and hydrogel formation
2Stability of the object's composition
If EHS mouse basement membrane extracts are used, then the hydrogels can be produced with some structural organization, but they have unnatural protein compositions compared to human tissue
Solution Approach 1:
The patent uses human tissue samples specifically for producing hydrogels intended for human applications, ensuring the protein composition and structural characteristics are locally optimized for human biocompatibility rather than using universal animal-derived materials
Solution Approach 2:
The patent creates a copy of the natural human ECM structure and composition by extracting and reassembling human ECM proteins into hydrogel formulations that replicate the native tissue architecture and molecular composition
3Ease of manufacture
If synthetic polymers modified with collagen peptide residues are used, then the hydrogels can be produced with controlled properties, but they lack the complexity of natural tissue
Solution Approach 1:
The patent creates composite hydrogel materials that combine purified ECM proteins with appropriate crosslinking agents and additives to achieve both the structural complexity of natural tissue and the manufacturability needed for controlled property adjustment
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 produces ECM hydrogels that accurately model natural tissues, support natural angiogenesis, are recognized by the host immune system, and promote cell attachment, enabling complex cell-based assays and organ-on-chip cultures.
Implementation Method 1
Depolymerizing may include mixing a decellularized tissue mesh with a depolymerizing solution including a chaotropic agent and a surfactant to form a depolymerizing mixture
Implementation Method 2
Gelling may include combining a sol with a gelling solution comprising a kosmotropic agent
Implementation Method 3
A method may include adding a hygroscopic agent to a gelling solution to modulate a stiffness of an extracellular matrix hydrogel
Data Source
AI summary
The present disclosure relates to a method for producing an extracellular matrix hydrogel, the method comprising (a) decellularizing a tissue sample to form a decellularized tissue mesh; (b) depolymerizing the decellularized tissue mesh to form a depolymerized protein dispersion, the depolymerizing comprising mixing the decellularized tissue mesh with a depolymerizing solution comprising a chaotropic agent to form a depolymerizing mixture; mechanically homogenizing the depolymerizing mixture at a chilled temperature to form a homogenized mixture; separating the homogenized mixture into (a) a waste precipitate and (b) a supernatant comprising the depolymerized protein dispersion; (c) filtering the depolymerized protein dispersion to form a sol; and (d) gelling the sol to form the extracellular matrix hydrogel, the gelling comprising combining the sol with a gelling solution comprising a kosmotropic agent; and separating a fluid phase away from the extracellular matrix hydrogel as it forms.