Cascia

Biophotonics

 

"Every day you play with the light of the universe."

Carlos Neruda

Biophotonics

Biophotonics is the study of interactions between electromagnetic radiation and biological or synthetic materials, including tissues, cells, and molecules in living organisms.  Virtually all biological species are profoundly affected by exposure to light, especially wavelengths in the visible portions of the spectrum, and Cascia is focused on using light from tunable optical devices to improve the therapeutic efficacy of our cellular treatments.

Light affects cells in a variety of ways with different organelles and structures responding to different wavelengths.



In a similar way, biocompatible materials respond in a predictable manner to changes in wavelength or intensity. In some hydrogel constructs, which can be used to deliver cells into damaged tissue, the tensile strength and resorbtion characteristic can be made stiffer with exposure to blue light or softer by exposure to ultraviolet wavelengths. As the tensile strength of the implant has effects on the implanted cells through mechanotransduction (a sensing by the cell of its environment), cells can be directed to form a particular type of tissue.




We intend to use biophotonics is a variety of ways to improve the efficacy of our products.



Laser induced photoporation can be used to introduce a number of substances into the cell itself, whether those are cellular lasers, drugs, biological molecules, fluorescent quantum dots, or SPIO (super paramagnetic iron oxides) particles. SPIO particles are of particular interest because they allow tracking of cell fate after the stem cells are implanted into a tissue or an organ. An SPIO particle is extremely small, about 30 nm, and they appear clearly on T2 MRI images. As the cells divide, the particles are split between the mother and daughter cells, allowing tracing of cell replication with a non invasive method. When the cells eventually die, the particle itself, which is just a form of elemental iron, it resorbed into the spleen or liver as part of the normal iron cycle.





One drawback of light is that it rapidly attenuates in tissue, especially in dark skinned individuals. This limits the usefulness of light to treat and observe diseased tissue more than a few centimeters thick. It is possible to created step index waveguides, similar to a glass fiberoptic, entirely out of biological materials that transmit light more than 10 cm into a tissue, making them practical for human use. These waveguides can be implanted with one end embedded deep in the tissue and the other end near the skin surface. When light is conducted down the waveguide, it can illuminate the diseased tissue, and if a pair of waveguides are used, one can be used to illuminate the tissue and the other can be used to monitor the back scattered light from intracellular lasers, fluorescent quantum dots, or other materials.




The behavior of stem cells can be altered a number of different ways. Mechanotransduction in response to environmental cues was discussed above, but light can also alter cellular level responses to cryptochrome, one of the four groups of mammalian clock genes/proteins that generate a transcription-translation negative-feedback loop. When cells are exposed to low level light, even for a few minutes, the deposition of calcium and phosphorous was increased, and maturation of cells into particular tissue types, such as bone, is increased.







Light can be used to initiate cross linking of hydrogels, and it can also be used in a bi directional manner to reverse links. Hydrogels made from particular materials, such as poly(ethylene glycol) (PEG) maleimide, can change their conformation when exposed to particular wavelengths of light or darkness, effectively creating a “on off” switch that modulates accumulation of mechanosensing signalling proteins in a concentration dependent manner. Light can also be used to induce cross linking of particular materials (seen in the image at right) where a silicone elastomer is formed by expose to UV light that incorporates anti-microbial properties.





Microneedles are used to deliver drugs or cellular material directly into an organ or, more commonly, into the epidermis via skin adherent patches. This allows the desired substance to be absorbed directly into the capillary bed, thereby eliminating gastric digestion or first pass metabolism by the liver. Using TPP (two photon polymerization) techniques, nanoscale objects can be formed in practically any shape from medical grade thermoplastics extruded by a bioprinter. In this example an open channel microneedle array is connected via side channels to nanoliter fluid reservoirs filled with drug.