Mesh Rolled Scaffold Bioreactor for Low-Shear Cell Expansion
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Solution Overview
Problem
Current bioreactors face challenges in large-scale culturing of adherent cells due to issues such as hydrodynamic shear stress, inefficient nutrient and gas transport, and the inability to separately treat media from cells, leading to unreliable cell expansion and media processing.
Innovation Solution
The development of a mesh rolled scaffold device and bioreactor system that utilizes a cylindrical scaffold constructed from alternating layers of planar film and mesh netting, allowing for uniform mass transfer and reduced shear stress, along with integrated components like dialyzers and heat exchangers for media processing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If the capacity of a bioreactor is increased to support large-scale cell culture, then the cell production capacity is improved, but the surface-to-volume ratio decreases and hydrodynamic shear stress increases, worsening cell viability and proliferation
Solution Approach 1:
The bioreactor is segmented into multiple compartments, each containing a mesh rolled scaffold with a high surface-to-volume ratio. This segmentation allows the system to maintain favorable surface-to-volume ratios in each compartment while achieving large overall capacity through multiple compartments, thereby reducing hydrodynamic shear stress on cells at the local level while maintaining high cell production capacity system-wide
Solution Approach 2:
The invention transitions from traditional two-dimensional planar culture surfaces to a three-dimensional mesh rolled scaffold structure. This dimensional change creates a cylindrical rolled scaffold with alternating film and mesh netting layers that provides high surface area within a compact volume, improving surface-to-volume ratio and reducing shear stress effects while maintaining high cell production capacity
2Quantity of substance
If vigorous stirring and aeration are applied to maintain mass transfer rate for large numbers of cells, then nutrient and gas transport is improved, but hydrodynamic shear stress increases, worsening cell proliferation and viability
Solution Approach 1:
The mesh rolled scaffold provides locally optimized mass transfer conditions through its porous structure, allowing nutrients and gases to diffuse efficiently to cells embedded within the scaffold matrix. This local mass transfer optimization reduces the need for vigorous bulk stirring, thereby maintaining cell viability while achieving adequate nutrient and gas transport
Solution Approach 2:
The mesh rolled scaffold acts as an intermediary structure between the bulk culture medium and the cells. It facilitates mass transfer of nutrients and gases to cells through its porous network while protecting cells from direct exposure to high shear stress conditions in the bulk medium, thus maintaining both mass transfer rate and cell viability
3Object-affected harmful factors
If cells are placed inside protective microstructures to shield them from hydrodynamic shear stress, then cell viability is improved, but uniform availability of nutrients and gases to all cells deteriorates
Solution Approach 1:
The mesh rolled scaffold utilizes a porous structure composed of alternating film and mesh netting layers that provides both mechanical protection from shear stress and adequate porosity for mass transfer. The porous architecture allows nutrients and gases to diffuse uniformly throughout the scaffold while the mesh structure shields embedded cells from hydrodynamic shear stress
Solution Approach 2:
The scaffold is constructed as a composite structure with alternating layers of film and mesh netting materials. This composite architecture combines the protective qualities of the mesh structure with the mass transfer properties of the porous film layers, achieving both shear stress protection and uniform nutrient/gas availability
4Quantity of substance
If traditional stirred bioreactors are used for large-scale cell culture, then cell production capacity is improved, but the ability to treat media separately from cells is lost, worsening media processing efficiency
Solution Approach 1:
The system segments cells and media into separate compartments: cells are contained within the mesh rolled scaffold while media circulates in the external bioreactor vessel. This spatial segmentation enables independent processing of media (through dialysis, heating, cooling, or filtration) without removing the scaffold-containing cells from the culture system, thereby maintaining high cell production capacity while improving media processing efficiency
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 system provides a high surface-to-volume ratio for large-scale cell culture with reduced shear stress, uniform nutrient and gas distribution, and the ability to process media independently, enhancing the reliability and efficiency of cell expansion and media treatment.
Implementation Method 1
The system provides a high surface-to-volume ratio for large-scale cell culture
Implementation Method 2
reduced shear stress
Implementation Method 3
uniform mass transfer and reduced shear stress
Implementation Method 4
integrated components like dialyzers and heat exchangers for media processing
Data Source
AI summary
The present invention provides mesh rolled scaffold devices and bioreactor systems that can provide a large surface-to-volume ratio for expanded cell culture. The mesh rolled scaffolds minimize shear stress on cultured cells and support sufficient and uniform mass transfer rates of gases and nutrients. The mesh rolled scaffolds can be connected to a media source via holders in bioreactor systems to support large-scale expansion and maintenance of cell cultures. The present invention also provides the bioreactor systems that can include dialyzers and heat exchangers to modify media and other fluids passing through the systems. The bioreactor systems include media and other fluid reservoirs that can support high stirring rates between about 100 and 10000 rpm, and the overall systems can be pressurized between about 1 and 10 atm to increase gas exchange rates.