Anchored Cell Sheet Remodeling for Stable 3D Constructs
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Solution Overview
Problem
Detached cell sheets tend to fold and form crumpled agglomerates over time, reducing cell viability and functionality, and are difficult to manipulate for in vivo applications due to uncontrolled shape transformation and fragility.
Innovation Solution
A cell culture device with a membrane and anchors is used to grow cell constructs, where cells attach, fuse, and remodel into a different shape attached to anchors, allowing controlled remodeling into stable 3D constructs without external scaffolds.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If cell sheets are detached from substrate and cultured without anchor, then cell sheets can be moved for in vivo application, but cell sheets fold and form crumpled agglomerates reducing cell viability and functionality
Solution Approach 1:
The patent introduces anchors as intermediary structures that mediate between the cell sheet and the external environment. These anchors provide a stable attachment point that prevents uncontrolled folding and agglomeration, thereby maintaining cell viability while still allowing the construct to be manipulated and transferred for in vivo applications.
Solution Approach 2:
The patent changes the physical state and configuration parameters of the cell construct by introducing anchored support points. This transforms the cell sheet from a completely free-floating fragile structure into an anchored construct with controlled geometry, preventing harmful crumpling while maintaining manipulability.
2Adaptability or versatility
If cell sheets are detached from substrate, then cell sheets can be used for in vivo applications, but the transformation to agglomerates is irreversible and sheets become fragile
Solution Approach 1:
Anchors serve as intermediary support structures that maintain structural integrity during manipulation and transfer. The anchors prevent irreversible transformation into agglomerates by providing stable attachment points that preserve the sheet-like or 3D construct architecture throughout the process.
Solution Approach 2:
The anchored structure provides beforehand cushioning and protection against the harmful effects of uncontrolled folding and mechanical stress during manipulation. This pre-established support system prevents structural failure before it occurs during transfer and implantation procedures.
3Stability of the object's composition
If cell layers remain attached to planar substrate in bioreactor, then cell sheets are stable, but cells have unnatural basal-apical morphology not representing in vivo cells
Solution Approach 1:
The anchors act as intermediary support structures that replace the planar substrate attachment. This allows cells to maintain stable attachment while adopting more natural 3D morphologies and orientations that better represent in vivo conditions, as the anchors provide point-based support rather than continuous planar contact.
Solution Approach 2:
The patent transitions from 2D planar substrate attachment to 3D anchored construct configuration. This dimensional change allows cells to develop more physiologically relevant basal-apical morphology and spatial organization while maintaining stability through the anchored support structure.
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 stable, physiologically relevant 3D cell constructs with aligned cells and ECM, suitable for in vitro modeling and in vivo applications like regenerative medicine, maintaining cell functionality and ease of manipulation.
Implementation Method 1
cells are grown, optionally in layers, and attach or fuse to each other to form a cell sheet
Implementation Method 2
a membrane and a plurality of anchors... The membrane may be treated or formed to first allow cell attachment and then to facilitate detachment of cells and their secreted ECM as a cell sheet from the membrane
Data Source
AI summary
Scaffold-free cell constructs are made from cell sheets. A device has a membrane and anchors located inside of a perimeter or wall of the membrane. The membrane allows cell attachment followed by detachment of cells and secreted ECM as a cell sheet. In a method, cells are grown into a cell sheet. The cell sheet is located around two or more anchors. The cell sheet remodels into a cell construct of a different shape attached to the anchors. When a cell sheet is grown in the device, the anchors form and pass through openings in the cell sheet. Detaching the cell sheet locates the cell sheet around the around the anchors. The cell construct can be used with or without decellularization and while attached to the anchors, for example as in vitro models, or after being removed from the anchors, for example in regenerative medicine or tissue engineering.