Magneto-mechanical biomedicine for pain modulation and immuno-engineering

Imperial College London

Programmable magnetic hydrogels for pain. Chronic pain is a debilitating disease affecting one-third of UK’s population. Unfortunately, existing surgical, opioid and electrical treatments are expensive, addictive and non-specific. There is an urgent need for innovative pain medicine.

There are different types of chronic pain and in several sub-types, the spinal cord neurons of patients express an unhealthily large numbers of mechano-sensitive channels (MSCs). MSCs are membrane proteins that convert mechanical forces into electrical signals. When they are too many of them, neural circuits become over-sensitive to forces, easily causing over-excitations of circuits. Andy discovered a phenomenon where neural circuits decrease their numbers of MSCs to restore homeostasis after being continually stimulated with mechanical forces. This provides a unique opportunity to exploit homeostatic tendencies of neurons for pain modulation. To design the ideal neuron-material interface, he synthesized magnetic hydrogels with similar biochemical/mechanical properties as the spinal cord tissues using FDA-approved ingredients. The hydrogels are also magnetic which enable non-invasive magneto-mechanical neuro-modulation.

Andy found that with chronic neural stimulation, diseased neurons started expressing healthy numbers of MSCs which contribute to pain. His work introduces a unique biophysical lens to modulate pain.

Nano-scale magnetic materials for T-cell transformation Cancer immunotherapy exploits engineered T-cells to detect and eliminate cancer cells from the body. Despite advances in genetic engineering, their successes depend on the process of introducing cargo such as DNA to genetically edit T-cells. Unfortunately, existing gold-standard techniques using viruses and bulk electroporation can cause cell stresses, elicit severe immune responses while providing only low transformation efficiency.

Andy fabricated nano-tubes (50,000x smaller than a rice grain) which T-cells rest gently on. Application of electric fields through the nano-tubes created pores on cell membrane for DNA delivery. Magnetic forces then preferentially transported DNA into nuclei. This technique is named magnetic nano-electro-injection (MagNEI). MagNEI is a gentler and more efficient technique to genetically engineer T cells compared to commercially- used viruses and bulk electroporation. With MagNEI, T-cell transformation efficiency can reach up to 40% with lower cell stress. This allows cells with higher quality to be used for cancer immunotherapy.

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