Engineered Extracellular Matrices with Controlled Fibril Properties
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Solution Overview
Problem
It has been challenging to obtain a lyophilized composition that maintains bioactivity for the mass production of solubilized extracellular matrix components for specific tissue graft applications, as existing methods fail to preserve the ability of these components to form fibrils in vitro and remodel tissue in vivo.
Innovation Solution
The method involves solubilizing extracellular matrix material with an acid, followed by systematic variation of polymerization conditions such as pH, phosphate concentration, temperature, buffer composition, and ionic strength to form engineered matrices with specific micro-structural and mechanical properties, including controlled collagen fibril area fraction and elastic modulus, which are then lyophilized to maintain bioactivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If existing lyophilization methods are used on extracellular matrix components, then the composition can be preserved for storage, but the bioactivity and ability to form fibrils in vitro are lost
Solution Approach 1:
The patent applies parameter changes by systematically varying lyophilization conditions including pH (adjusted to specific ranges), temperature (controlled during freezing and drying phases), and chemical additives (such as sugars or amino acids as cryoprotectants) to preserve the bioactivity of extracellular matrix components while achieving stable storage. These parameter modifications prevent denaturation and maintain the ability to form fibrils after lyophilization.
2Productivity
If solubilized extracellular matrix components are processed for mass production, then quantity and consistency are improved, but the ability to remodel tissue in vivo is compromised
Solution Approach 1:
The patent applies preliminary action by pre-forming collagen fibrils under controlled conditions before lyophilization. The method involves allowing solubilized collagen to self-assemble into fibrillar structures at specific pH and temperature ranges prior to the lyophilization process, thereby preserving the fibril-forming capability and tissue remodeling ability in the final dried product while enabling consistent mass production.
Solution Approach 2:
The patent systematically controls multiple parameters during processing including pH (maintained in specific ranges to favor fibril formation), temperature (controlled during both fibril formation and lyophilization), ionic strength, and concentration of extracellular matrix components. These parameter changes ensure that the processed material retains bioactivity and tissue remodeling capability while achieving consistent mass production.
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 approach allows for the production of bioactive, lyophilized extracellular matrix components that can be used to create engineered matrices with desired properties for tissue graft applications, enhancing tissue repair and regeneration by promoting cell proliferation, migration, and differentiation.
Implementation Method 1
systematic variation of polymerization conditions... to form engineered matrices with specific micro-structural and mechanical properties, including controlled collagen fibril area fraction
Implementation Method 2
lyophilized to maintain bioactivity
Data Source
AI summary
The invention relates to engineered matrices comprising collagen fibrils with specific characteristics, including, but not limited to, a specific fibril area fraction (i.e., density) and/or a specific elastic or linear modulus (i.e., stiffness). The invention also relates to methods of preparation and use of the matrices.