A Comprehensive Analysis of Near‐Contact Photobiomodulation Therapy in the Host–Bacteria Interaction Model Using 3D‐Printed Modular LED Platform

Abstract

One well‐studied bacterial factor recognized by the host immune system is lipopolysaccharides (LPS) that stimulate host cells, resulting in cell inflammation. Although photobiomodulation (PBM) therapy demonstrates its potency on anti‐inflammatory activity, the complete mechanism of action in the host–bacteria interaction model is still elusive. In addition, many studies were performed regarding a distance between the light source and biological sample (non‐contact therapy) that may result in disparate reports on the efficacy of PBM therapy. Thus, it is critical to clearly understand the effect of this approach to maximize efficacy and minimize side effects. Here, a custom‐built light‐emitting diode (LED) platform that mimics near‐contact therapy is developed. The effect and mechanism of PBM therapy on epithelial cells in response to LPS is systematically investigated under various conditions (wavelength, irradiation‐time, pulse‐frequency). The data show that the irradiation of near‐infrared (NIR‐LED) significantly improves the viability of inflamed cells. It reveals that NIR‐LED inhibits the production of reactive oxygen species by regulating the Nox4‐NF‐κB pathway. Interestingly, however, high‐pulse frequency stimulus causes the collapse of the mitochondrial membrane potential (ΔΨm) of cells, resulting in cell death. These results suggest that the optimized “PBM condition” is critical to assist the healthy immune system of the host against bacterial invasion.

A dental implant-on-a-chip for 3D modeling of host–material–pathogen interactions and therapeutic testing platforms

“…In our previous study, we investigated the effects of blue, green, red, and near-infrared light on HGK numbers that were infected with lipopolysaccharides. 22 We observed that red or near-infrared light significantly increased cell numbers relative to non-irradiated controls. 22,31 In contrast, green light did not affect cell proliferation, whereas blue light caused extensive photocytotoxicity.…”

“…22 We observed that red or near-infrared light significantly increased cell numbers relative to non-irradiated controls. 22,31 In contrast, green light did not affect cell proliferation, whereas blue light caused extensive photocytotoxicity. 22 To corroborate our previous findings of the protective effect of PBM therapy on keratinocytes and to demonstrate the amenability of our system with PBM-based investigations, we utilized red light and tested chips under two conditionswith and without LED treatment before the bacterial challenge.…”

“…55,56 In fact, we have previously evaluated nearcontact PBM therapy on keratinocytes in vitro and investigated its efficacy on host-pathogen interactions. 22 Additionally, we have developed a smart dental implant system for PBM therapy on gingival keratinocytes. 31 Thus, the IOC model combined with the PBM therapy module can be a useful tool to test the efficacy of PBM therapy in preventing implant infection and serves as a logical extension of our previous work.…”

“…Our custom chip-holder was a miniaturized form of a LED platform that we have previously optimized for use in host–pathogen investigations. 22 Briefly, red LEDs ( λ = 615 nm; SML-P12U2TT86R, ROHM Semiconductor, UK) were used on a miniaturized LED platform that was fabricated by connecting a resistor in series with an LED (1.2 kΩ) to limit the current and protect the electronics. Irradiance was kept consistent with our previous study 22 by using the irradiation profile in Fig.…”

“…Using insulated wires (29 AWG), the LED circuit was connected to a power supply as described previously. 22 Bacterial challenge and photobiomodulation experiments S. mutans UA159, a cariogenic oral pathogen, was used for bacterial challenge experiments. Stocks were stored at −80 °C in tryptic soy broth containing 50% glycerol.…”