Electrospun PDMS-PCL Mesh for T Cell Expansion Stiffness Control
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Solution Overview
Problem
Current immunotherapy technologies face challenges in optimizing surface and matrix rigidity for T cell expansion, which is crucial for adoptive immunotherapy, as existing rigid substrates do not mimic the in vivo environment and can impact T cell activation, proliferation, and differentiation.
Innovation Solution
The use of electrospun mesh substrates composed of polydimethylsiloxane (PDMS) and polycaprolactone (PCL) with tunable fiber diameters and pore sizes, offering a biocompatible platform with adjustable stiffness to enhance T cell and stem cell expansion, while maintaining a high surface area-to-volume ratio.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If rigid substrates (polystyrene plastic, glass) are used for T cell culture, then structural stability is maintained, but T cell activation and proliferation are impaired due to unnatural stiffness
Solution Approach 1:
The patent applies parameter changes by systematically varying the elastic modulus of substrates across a range (100 kPa to 10 MPa) to identify optimal stiffness for T cell expansion. This involves changing the physical parameter of substrate rigidity to match in vivo conditions, thereby improving T cell activation and proliferation while maintaining structural stability.
Solution Approach 2:
The patent employs composite materials by combining different polymer components to create substrates with tailored mechanical properties. This allows the substrate to achieve an optimal balance between structural integrity and physiological stiffness, resolving the contradiction between reliability of cell activation and excessive substrate strength.
2Productivity
If high surface area-to-volume ratio substrates are used to enhance cell expansion, then cell proliferation is improved, but control over surface rigidity becomes more difficult
Solution Approach 1:
The patent applies dynamics by creating tunable substrates where surface rigidity can be adjusted according to specific cell culture requirements. This dynamic adjustment capability allows the substrate to simultaneously provide high surface area for cell expansion while maintaining controllable rigidity, resolving the contradiction between productivity and device complexity.
3Reliability
If soft substrates (E < 100 kPa) are used to mimic in vivo environment, then T cell signaling is improved, but structural stability and ease of handling are reduced
Solution Approach 1:
The patent applies parameter changes by precisely controlling the elastic modulus within the soft range (100 kPa to 10 MPa) to optimize T cell signaling while maintaining sufficient structural stability. This involves adjusting physical parameters of the substrate to achieve the optimal balance between softness for cell signaling and rigidity for handling.
Solution Approach 2:
The patent employs composite materials to create substrates that combine soft polymer components with structural reinforcement elements. This composite approach allows the substrate to provide the soft mechanical environment needed for improved T cell signaling while maintaining adequate structural stability and ease of handling through material composition design.
Data Source
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AI summary
The disclosure provides for compositions, systems, and methods of cell expansion, stimulation and/or differentiation. The disclosure further provides for a mesh substrate and associated methods capable of stimulating cell expansion, for example, T cell or stem cell expansion. In another aspect, the disclosure provides for an electrospun mesh substrate and methods of using thereof comprising a silicone rubber composition, for example, polydimethylsiloxane, PLC, or combinations thereof.