Abnormal response of costal chondrocytes to acidosis in patients with chest wall deformity.

Costal cartilage is much understudied compared to the load bearing cartilages. Abnormally grown costal cartilages are associated with the inherited chest wall deformities pectus excavatum and pectus carinatum resulting in sunken or pigeon chest respectively. A lack of understanding of the ultrastructural and molecular biology properties of costal cartilage is a major confounder in predicting causes and outcomes of these disorders. Due to the avascular nature of cartilage, chondrocytes metabolize glycolytically, producing an acidic environment. During physical activity hydrogen ions move within cartilage driven by compressive forces, thus at any one time, chondrocytes experience transient changes in pH. A variety of ion channels on chondrocytes plasma membrane equip them to function in the rapidly changing conditions they experience. In this paper we describe reduced expression of the ASIC2 gene encoding the acid sensing ion channel isoform 2 (previously referred to as ACCN1 or ACCN) in patients with chest wall deformities. We hypothesized that chondrocytes from these patients cannot respond normally to changes in pH that are an integral part of the biology of this tissue. Activation of ASICs indirectly creates a cascade ultimately dependent on intracellular calcium transients. The objective of this paper was to compare internal calcium signaling in response to external pH changes in costal chondrocytes from patients with chest wall deformities and healthy individuals. Although the molecular mechanism through which chondrocytes are regulated by acidosis remains unknown, we observed reduced amplitudes of calcium rise in patient chondrocytes exposed to low pH that become further impaired upon repeat exposure.

Control of optical transparency and infrared laser heating of costal cartilage via injection of iohexol.

Infrared (IR) laser impact has no analogues for rapid and safe cartilage reshaping. For better penetration of radiation optical clearing agents (OCAs) can be applied. In present work, the effect of low-osmolality agent iohexol on costal cartilage is studied. Specifically, it is shown that ½ of total increase of optical transparency occurs in 20 minutes of immersion. Maximally, cartilage transparency on 1560 nm can be increased in 1.5 times. Injection of iohexol results in increased tissue hygroscopicity, lower drying rate and higher percentage of bound water. Effective diffusion coefficients of water liberation at 21°C are (5.3 ± 0.4) × 10-7 and (3.3 ± 0.1) × 10-7 cm2 /s for untreated and iohexol-modified tissue, respectively. Raman spectroscopy of irradiated iohexol solution reveals its photo and thermo-stability under clinically used IR laser energies up to 350 W/cm2 for exposure times of several seconds. At energies higher than 500 W/cm2 [Correction added on 5 September 2018, after first online publication: This unit has been changed] decomposition of iohexol occurs rapidly through formation of molecular iodine and fluorescent residue.

Controlling the near-infrared transparency of costal cartilage by impregnation with clearing agents and magnetite nanoparticles.

Penetration depth of near-infrared laser radiation to costal cartilage is controlled by the tissue absorption and scattering, and it is the critical parameter to provide the relaxation of mechanical stress throughout the whole thickness of cartilage implant. To enhance the penetration for the laser radiation on 1.56 µm, the optical clearing solutions of glycerol and fructose of various concentrations are tested. The effective and reversible tissue clearance was achieved. However, the increasing absorption of radiation should be concerned: 5°C-8°C increase of tissue temperature was detected. Laser parameters used for stress relaxation in cartilage should be optimized when applying optical clearing agents. To concentrate the absorption in the superficial tissue layers, magnetite nanoparticle (NP) dispersions with the mean size 95 ± 5 nm and concentration 3.9 ± 1.1 × 1011 particles/mL are applied. The significant increase in the tissue heating rate was observed along with the decrease in its transparency. Using NPs the respective laser power can be decreased, allowing us to obtain the working temperature locally with reduced thermal effect on the surrounding tissue.