Automated ECM Scaffold Decellularization With Freeze-Thaw Cycles
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Solution Overview
Problem
Current decellularization protocols for extracellular matrix (ECM) scaffolds are lengthy, disruptive to ECM components, and lack standardization, leading to variability in product quality and reproducibility, which hinders their widespread clinical and research applications.
Innovation Solution
An automated decellularization system using a bioreactor with inline filtration, stirring mechanism, and controlled reagent dosing, along with real-time monitoring, to optimize the decellularization process, reducing exposure time and maintaining ECM integrity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If prolonged exposure to chemical or biological washes is used for decellularization, then cellular content is effectively removed, but ECM components are disrupted and bioactivity decreases
Solution Approach 1:
The patent applies periodic action by using cyclic freezing and thawing conditions to achieve decellularization. The tissue is subjected to repeated freeze-thaw cycles that mechanically disrupt cellular structures while preserving ECM integrity, eliminating the need for prolonged chemical exposure that would damage ECM components.
Solution Approach 2:
The patent replaces chemical and biological washes with a physical mechanism (freezing and thawing) to achieve decellularization. This mechanical substitution avoids the use of chemicals that disrupt ECM ultrastructure while effectively removing cellular content through ice crystal formation and mechanical stress.
2Adaptability or versatility
If manual decellularization protocols are used, then flexibility in protocol optimization is maintained, but production time is prolonged and variability increases
Solution Approach 1:
The patent changes the fundamental parameter of decellularization from chemical concentration and exposure time to freezing temperature and thawing duration. This parameter change enables standardized automated processing while maintaining protocol adaptability, as the freeze-thaw cycles can be easily adjusted for different tissue types without requiring complex chemical protocol optimization.
3Reliability
If chemical decellularization reagents are used, then cellular and nuclear content is removed, but ECM ultrastructure is affected and collagens are damaged
Solution Approach 1:
The patent replaces chemical reagents with a mechanical process involving freezing and thawing. The mechanical stress from ice crystal formation and thermal expansion/contraction effectively removes cellular content while preserving the ECM ultrastructure and collagen integrity, avoiding the damaging effects of chemical detergents and enzymes.
Solution Approach 2:
The patent utilizes phase transitions of water (freezing and thawing) as the decellularization mechanism. The repeated transitions between solid and liquid phases create mechanical stress that disrupts cellular structures and releases cellular content while leaving the ECM framework intact and bioactive.
Data Source
AI summary
Provided herein are systems, devices and methods to automate and optimize the decellularization process of representative tissues, such as soft tissues, for extracellular matrix (ECM)-based scaffold and biomaterial production. The automated decellularization processes and devices significantly reduce the exposure time to reagents, minimize lot-to-lot variability, and largely preserve the native composition of the ECM from the decellularized tissue or species.