Extracellular Matrix Hydrogel Terminal Sterilization via Lyophilization
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Solution Overview
Problem
Terminal sterilization of extracellular matrix (ECM) scaffolds inhibits the formation of ECM-derived hydrogels, which are essential for clinical translation and commercialization.
Innovation Solution
Changing the form of ECM material prior to sterilization from a solid sheet to a lyophilized ECM digest facilitates hydrogel formation. This involves freeze-drying the ECM digest, sterilizing the dried material using ethylene oxide gas or other methods, and then reconstituting it in water to produce a gel that reproducibly forms at 37°C.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ECM scaffolds are terminally sterilized using conventional methods (ethylene oxide gas, gamma irradiation, or electron beam radiation), then sterilization is achieved, but hydrogel formation is inhibited
Solution Approach 1:
The ECM material is freeze-dried and sterilized before reconstitution and hydrogel formation. This preliminary sterilization of the dry material prevents microbial contamination during storage and handling, while the sterilization occurs before the hydrogel formation step, thus avoiding interference with the gelation process. The dry state appears to protect the material's ability to form hydrogels after sterilization.
Solution Approach 2:
The patent changes the physical state parameter of the ECM material from solid sheet to lyophilized (freeze-dried) form before sterilization. This parameter change enables the material to withstand terminal sterilization while retaining the capacity to form hydrogels subsequently. The lyophilized state appears to be more resistant to sterilization-induced damage than the solid sheet form.
2Strength
If ECM material is kept in solid sheet form for sterilization, then structural integrity is maintained, but hydrogel formation after sterilization is prevented
Solution Approach 1:
The patent changes the physical form parameter from solid sheet to lyophilized digest. This transformation maintains the structural integrity needed for handling and sterilization while fundamentally altering the material's properties to enable subsequent hydrogel formation. The lyophilized state creates a porous structure that can be reconstituted into hydrogels after sterilization.
Solution Approach 2:
The patent utilizes freeze-drying (lyophilization) to transition the ECM material from solid sheet to a porous dried state, then to hydrogel form after reconstitution. These phase transitions enable the material to survive sterilization in the dried state and then transform into the desired hydrogel form after sterilization, resolving the contradiction between maintaining structural integrity and enabling hydrogel formation.
3Reliability
If terminal sterilization is applied to ECM hydrogels, then clinical safety is ensured, but the beneficial degradation products are lost
Solution Approach 1:
The ECM material is sterilized in its lyophilized state before reconstitution and hydrogel formation, rather than sterilizing the formed hydrogel. This preliminary sterilization approach ensures clinical safety while preserving the ECM degradation products, as the sterilization occurs before the hydrogel is formed and before any potential loss of beneficial substances during hydrogel sterilization.
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
This method allows for reproducible gelation of ECM hydrogels even after terminal sterilization, enabling the development of sterilized, gelled, solubilized ECM compositions suitable for use as cell growth scaffolds.
Implementation Method 1
freeze-drying (lyophilizing) an ECM digest, sterilizing the dried digest
Implementation Method 2
sterilizing the dried digest by exposure to ethylene oxide gas
Implementation Method 3
reconstituting the dried pre-gel in water, produces a digest that reproducibly gels
Implementation Method 4
gelation when neutralized and incubated at 37° C.
Data Source
AI summary
Provided are methods for preparing sterilized, gelled, solubilized extracellular matrix (ECM) compositions useful as cell growth substrates. Also provided are compositions prepared according to the methods as well as uses for the compositions. In one embodiment a device, such as a prosthesis, is provided which comprises an inorganic matrix into which the gelled, solubilized ECM is dispersed to facilitate in-growth of cells into the ECM and thus adaptation and/or attachment of the device to a patient.