Generation of an induced pluripotent stem cell line from a late-onset, progressive high frequency hearing loss patient due to mutation in CDH23.

Cadherin 23 (CDH23) is one of the most common genes responsible for hereditary hearing loss; a mutation of CDH23 can cause a wide range of symptoms depending on the variant. In this study, an iPSC line was generated from a patient with late-onset, progressive high frequency hearing loss caused by c.[719C > T];[6085C > T]:p.[P240L];[R2029W] compound heterozygous variants of CDH23. The cells were confirmed to have a normal karyotype, express markers of pluripotency, and have tri-embryonic differentiation potential. This disease-specific iPSC line will further the construction of disease models and the elucidation of the pathophysiology of CDH23 mutations.

Generation and characterization of a human iPSC line (JUFMDOi007-A) from a patient with Usher syndrome due to mutation in USH2A.

Usher syndrome type 2A (USH2A) gene mutations have been identified as the most frequent genetic causes of hereditary deafness in Usher syndrome, and an effective treatment has yet to be established. The encoded protein, Usherin, is essential for the ankle link associated with extracellular connections between the stereocilia of inner ear hair cells. We report the generation of a patient-derived USH2A iPSC line with compound mutations c.1907_1912ATGTTT > TCACAG (p.D636V + V637T + C638G) and c.8328_8329delAA (p.L2276fs*12). The iPSC showed the expression of pluripotency markers, the ability to differentiate into three germ layers in vitro, and USH2A mutations with normal karyotype.

Enhancement of antibacterial property of titanium by two-step micro arc oxidation treatment.

A customized micro arc oxidation (MAO) treatment technique was developed to obtain desirable antibacterial properties on titanium surfaces. The two-step MAO treatment was applied to fabricate a specimen containing both Ag and Zn in its surface oxide layer. Surface analyses and metal-ion release tests were performed to evaluate the presence of Ag and Zn and the ion release behavior for simulating practical usage, respectively. Additionally, the antibacterial properties of the specimens were also evaluated using gram-negative facultative anaerobic bacteria. The MAO-treated specimens containing both Ag and Zn showed excellent antibacterial properties against Escherichia coli, and the properties were sustained even after 28 days of immersion in physiological saline to simulate the living environment.

Improvement of adhesive strength of segmented polyurethane on Ti-29Nb-13Ta-4.6Zr alloy through H2O2 treatment for biomedical applications.

The number of hydroxyl groups on a Ti-29Nb-13Ta-4.6Zr (TNTZ) alloy surface was controlled through H2O2 treatment for further improvement of the adhesive strength and durability against water of TNTZ/silane layers (SILs)/segmented polyurethane (SPU) composites. The effect of the terminal functional groups on the adhesive strength of SPU on TNTZ, and the adhesiveness of SPU on TNTZ against water was investigated. Three types of silane-coupling agents were used to bind TNTZ and SPU: methacryloxypropyltrimethoxysilane (γ-MPTS), aminopropyltriethoxysilane (APS), and mercaptopropyltrimethoxysilane (γ-MPS). The adhesive strength of each composite was evaluated by shear bonding tests. The number of hydroxyl groups increases with an increase in treatment time at a H2O2 concentration of 5% (v/v). On the other hand, an increase from 5% (v/v) to 30% (v/v) in H2O2 concentration leads to a decrease in the number of hydroxyl groups on the TNTZ surface because at higher H2O2 concentrations, the reaction that consumes the hydroxyl groups is dominant. The shear bonding strength is doubled compared with the untreated TNTZ/SIL/SPU interface. Although the shear bonding strength decreases after immersion in water for 30 days when APS and γ-MPS are used, TNTZ/γ-MPTS/SPU composites exhibit good durability to water and maintain an equivalent shear bonding strength before immersion in water.

Development of biomedical porous titanium filled with medical polymer by in-situ polymerization of monomer solution infiltrated into pores.

Porous metallic materials can have a low Young's modulus, which is approximately equal to that of human bone, by controlling the porosity. On the other hand, certain medical polymers exhibit biofunctionalities that are not intrinsically present in metallic materials. Therefore, a composite consisting of these materials is expected to possess both these advantages for biomedical applications. However, in the case of using porous metallic materials, the deterioration of mechanical properties should of concern because a stress concentration may be induced near the pores. In this study, for the fabrication of the abovementioned composite, a versatile process for filling a medical polymer into a porous metallic material has been developed using porous pure titanium (pTi) and polymethylmethacrylate (PMMA). Then, the tensile strength and Young's modulus of pTi filled with PMMA (pTi/PMMA) fabricated using this process are systematically investigated. The tensile strength of pTi can be improved by the PMMA filling. Particularly, the improvement in the tensile strength of pTi pretreated using a silane coupling agent before PMMA filling is greater than that of the non-pretreated pTi because the stress concentration near the pores may be reduced by the improvement in the interfacial adhesiveness between the titanium particles and the PMMA. In contrast, the effect of the PMMA filling on the Young's modulus of pTi is smaller than that on the tensile strength because the Young's modulus of PMMA is considerably lower than that of pTi. Further, tensile strengths and Young's moduli comparable to the tensile strength and Young's modulus of the human bone are successfully obtained in the case of some pTi/PMMA samples.

Calcification by MC3T3-E1 cells on RGD peptide immobilized on titanium through electrodeposited PEG.

The effect of a cell-adhesive peptide containing Arg-Gly-Asp (RGD) immobilized through poly(ethylene glycol) (PEG) on titanium (Ti) on calcification by MC3T3-E1 cells was investigated to develop a new surface modification technique using biofunctional molecules. RGD was immobilized on Ti through PEG, both terminals of which were terminated with -NH(2) and -COOH to combine with the Ti surface and RGD. PEG was immobilized on Ti with electrodeposition, and RGD, with immersion. For comparison, glycine was employed because it is the simplest molecule containing both -NH(2) and -COOH at its terminals. MC3T3-E1 cells were cultured and differentiation-induced on each specimen, and the cell calcification properties were investigated. As a result, there was no significant difference in the morphology and extension of MC3T3-E1 cells cultured on each specimen, while the number of cells cultured on RGD/PEG/Ti was the largest. After differentiation-induction, there was no significant difference in the ALP activity among all specimens. On the other hand, the level of cell calcification on RGD/PEG/Ti was the highest. Therefore, the hard tissue compatibility of Ti is improved by immobilizing RGD through functional molecules which have a long molecular chain.