Significance: Worldwide, ∼460 million people suffer from disabling hearing impairment. Many of these patients are still not sufficiently supplied with currently available auditory technologies. Optical stimulation of the hearing organ offers a promising alternative for a new generation of auditory prostheses.
Aim: To assess the biocompatibility margins of our laser pulse amplitude strategy in vitro, we designed a protocol and present the effects on normal human dermal fibroblasts, human chondrocytes, and human osteoblasts.
Approach: Laser pulses of 532 nm were applied over 120 s using our laser pulse amplitude modulation strategy. We then assessed cell viability and cytotoxicity through fluorescence staining and quantitative polymerase chain reaction-analysis regarding 84 key player-genes for cytotoxicity and stress response.
Results: The first in vitro biocompatibility margins for our stimulation parameters applied to cells of the peripheral hearing organ were between 200 and 223 mW (3348 J/cm2). After irradiation with a subphototoxic laser power of 199 mW (2988 J/cm2), only the fibroblasts showed a significant upregulation of GADD45G.
Conclusion: Further studies are underway to optimize parameters for the optoacoustic stimulation of the auditory system. Our protocol and results on laser–tissue interactions can be useful for translational laser applications in various other irradiated biological tissues.
Hearing impairment affects ∼460 million people worldwide. Conservative therapies, such as hearing aids, bone conduction systems, and middle ear implants, do not always sufficiently compensate for this deficit. The optical stimulation is currently under investigation as an alternative stimulation strategy for the activation of the hearing system. To assess the biocompatibility margins of this emerging technology, we established a method applicable in whole-mount preparations of murine tympanic membranes (TM). We irradiated the TM of anesthetized mice with 532-nm laser pulses at an average power of 50, 89, 99, and 125 mW at two different locations of the TM and monitored the hearing function with auditory brainstem responses. Laser-power-dependent negative side effects to the TM were observed at power levels exceeding 89 mW. Although we did not find any significant negative effects of optical stimulation on the hearing function in these mice, based on the histology results further studies are necessary for optimization of the used parameters.
The tympanic membrane (TM) separates the outer ear from the tympanic cavity. Repeated pathologies can permanently decrease its tension, inducing conductive hearing loss and adhesive processes up to cholesteatoma. The current main therapy is its surgical reconstruction. Even though lasers have been proposed to tighten atrophic TMs, details of this effect, specifically histological analyses, are missing. We therefore used laser pulses to induce TM collagen remodeling in an animal model to compare the histological and electrophysiological effects of different applied laser intensities before entering clinical studies. We irradiated Fuchsin-stained areas of the TM in anesthetized mice with 532-nm laser-pulses of 10 mW for 30 s (0.3 J), 25 mW for 30 s (0.75 J) or 50 mW for 30 s (1.5 J) monitoring hearing with auditory brainstem responses (ABRs). The mice were sacrificed after 2 to 8 weeks and histologically analyzed. An increase in the TM thickness within the defined, stained, and irradiated areas could be observed after 4 weeks. Polarized light microscopy and transmission electron microscopy demonstrated the tissue volume increase majorly due to new collagen-fibrils. Directly after irradiation, ABR thresholds did not increase. We herein demonstrate a controlled laser-induced collagen remodeling within defined areas of the TM. This method might be the prophylactic solution for chronic inflammatory ear pathologies related to decreased TM tension.
The interaction between biological tissues and light of a certain wavelength is influenced by the optical properties of each tissue. These are typically estimated from of the measurements of the main characteristics of the radiations pathway.
We herein present our approach that uses a customized version of the Monte Carlo Multi-Layer Algorithm (MCML)1 to simulate the radiation propagation through biological tissues. We assumed a set of optical properties for each tissue and simulated the above mentioned measurements in silico. A comparison was then done between the results of the simulation and the results of real measurements.2 Further, an optimization algorithm searched the set of optical properties that best fit the real optical properties of each tissue. This algorithm was based on adaptions of the Monte-Carlo Simulated Annealing algorithm3 and the Downhill Simplex algorithm4 We implemented the MCML using NVidias CUDA application programming interface to speed up the optimization procedure. We validated the software by using van de Hulsts table for Henyey-Greenstein scattering.2 A linear regression resulted in coefficients of determination between 0.929 and 0.973 for the optical properties. Our results prove that our algorithm can be effectively used for the determination of the optical properties of turbid media.
One first application for this software is the support in the development of a new generation of hearing devices based on optical energy.
Repeated pathologies of the tympanic membrane (TM) decrease its tension inducing conductive hearing loss and adhesive processes up to cholesteatoma. Our results regarding the development of a laser based noninvasive procedure to strengthen the structure of the TM are herein presented.