3D Packed Bed Bioreactor with ECM-Coated Porous Scaffold
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Solution Overview
Problem
Current systems for culturing immune cells are limited by high shear stress, low efficacy, limited scalability, and high costs, which can lead to cell damage and make them unsuitable for large-scale applications such as adoptive cell therapies.
Innovation Solution
A 3D packed bed bioreactor system using a porous stationary phase coated with Extra Cellular Matrix (ECM) and immune cell activators, which creates a low shear force environment that mimics the natural growth environment of immune cells, allowing for large-scale expansion and activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional bioreactor systems are used for large-scale immune cell culturing, then scalability is improved, but cell damage increases due to high shear stress
Solution Approach 1:
The patent employs a porous stationary phase (porous beads or scaffolds) as the support structure for immune cell attachment and growth. The porous structure provides a large surface area for cell attachment while allowing media flow through the interior pores, creating a low shear stress environment that protects cells from damage during large-scale culturing operations.
Solution Approach 2:
The invention transitions from traditional suspension or monolayer culture to three-dimensional packed bed structure. Immune cells are attached to and grow within the three-dimensional porous matrix, utilizing the vertical and radial dimensions of the bioreactor to achieve large-scale expansion without subjecting cells to high shear forces associated with mechanical agitation.
2Productivity
If immune cells are cultured in large scale, then productivity is improved, but manufacturing complexity increases
Solution Approach 1:
The bioreactor system is divided into distinct functional components: a packed bed chamber containing the porous stationary phase, media inlet and outlet systems, and optionally a separate activation chamber. This segmentation allows for modular design, easier manufacturing, and simplified operation while maintaining large-scale cell expansion capability.
Solution Approach 2:
The porous stationary phase acts as an intermediary structure that supports immune cell attachment and growth while allowing easy flow of media and nutrients. This intermediate matrix simplifies the overall system design by providing a passive support structure that eliminates the need for complex agitation or aeration systems required in traditional bioreactors.
3Ease of operation
If conventional culturing methods are used, then ease of operation is maintained, but cell activation efficacy decreases
Solution Approach 1:
The porous stationary phase is pre-coated with extracellular matrix proteins (such as collagen, fibronectin, or laminin) before immune cells are introduced. This preliminary coating creates an optimal surface for cell attachment and activation, enhancing cell activation efficacy while maintaining simple operation, as the coating process is performed once during bioreactor preparation rather than during each culturing cycle.
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 enables efficient and scalable expansion of immune cells with minimal damage, allowing for optimal cell growth and activation, which is critical for applications in immunotherapy.
Implementation Method 1
The porous element/s are positioned within a basket of a packed bed bioreactor and are not mobile, and do not move with the liquid flow that surrounds them and flow through them. The stationary phase can be implemented in various forms and aimed to create an environment with low flow and low shear forces.
Implementation Method 2
The porous element/s as will be described in detail hereinbelow are positioned within a basket of a packed bed bioreactor
Data Source
AI summary
This invention discloses a three-dimensional (3D) bioreactor for large scale expansion of immune cells and methods of use. The 3D bioreactor comprising at least one packed bed chamber comprising at least one porous scaffold; at least one porous scaffold coated with one or more extra cellular matrix protein (ECM); at least one container comprising a fluid media, the fluid media is configured to flow through said packed bed chamber with at least one porous coated scaffold; and at least one population of immune cells suspended in the fluid media, wherein, the at least one porous scaffold coated with said ECM is creates a stationary niche having low shear forces that imitate the natural growth environment of the immune cells and allows expansion of the immune cells population that flow through the coated porous scaffold in large scale.