SUMMARY
Bioelectronic devices and methods for the electrical stimulation of cells and engineered tissue for the scalable production of extracellular vesicles for drug delivery and regenerative medicine.
The Unmet Need: New techniques for mass production of extracellular vesicles
- Extracellular vesicles (EVs) are important membrane-enclosed organelles that found in almost all biological fluids and produced by myriad cell types. EVs are highly varied in cargo, size, and profiles, enabling the diagnosis of various diseases through an analysis of a patient’s EV profile. EVs also work as important drug delivery vehicles in regenerative medicine and anti-tumor treatments.
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To apply EVs as clinically relevant therapeutic tools, EVs should contain bioactive ingredients necessary for therapeutic action. In addition to the quality of the content, EVs should be mass-produced to reach enough quantity. However, until now, accumulating enough therapeutic EVs in vitro has proven difficult due to the limited number of EVs can be generated per cell.
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Currently, mass production of EVs involves isolating EVs from biological fluids, such as blood, urine, and saliva, which ends up collecting heterogeneous EVs from multiple cell origin. It is still challenging and of significant concerns to create EV carriers with constant characteristics and properties on a large scale for encoding biopharmaceutical cargos. Therefore, new strategies to produce sufficient EVs carriers from sole cell sources on a large scale are still required.
The proposed solution: A new bioelectronic device to promote EV generation without damaging cellular penetration
- The faculty inventor developed a bioelectronic device for electrical stimulation and modulation of cells for enhanced release of EVs without affecting cell viability. The device consists of planar extracellular microelectrode arrays dispose on the substrate and a controller electronically coupled to the electrodes and configured to apply an electrical stimulation sufficient to induce generation of EVs disposed on the substrate without killing the cells.
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The scalable production occurs in a device chamber connected to continuous flow systems for delivering solution and collecting EVs produced by cells. Additionally, the chamber comprises an inlet for inflow of culture media into the chamber and an outlet for outflow of spent culture media and EVs generated by cells disposed within the chamber. The device presents an alternative to electroporation methods where cell membranes are damaged during the electrical stimulation.
ADVANTAGES
ADVANTAGES
- Scalability, larger throughput
- Continuous flow system to collect EVs produced by cells over an extended period
- Reduced cell membrane damage
APPLICATIONS
- Regenerative medicine
- Drug delivery
November 13, 2024
Proof of concept
Patent Pending
Licensing,Co-development
Bozhi Tian