Gypsum-Related Impact on Antibiotic-Loaded Composite Based on Highly Porous Hydroxyapatite-Advantages and Disadvantages.

Highly porous hydroxyapatite is sometimes considered toxic and useless as a biomaterial for bone tissue regeneration because of the high adsorption of calcium and phosphate ions from cell culture media. This negatively affects the osteoblast's growth in such ion-deprived media and suggests "false cytotoxicity" of tested hydroxyapatite. In our recent study, we showed that a small addition of calcium sulfate dihydrate (CSD) may compensate for this adsorption without a negative effect on other properties of hydroxyapatite-based biomaterials. This study was designed to verify whether such CSD-supplemented biomaterials may serve as antibiotic carriers. FTIR, roughness, mechanical strength analysis, drug release, hemocompatibility, cytotoxicity against human osteoblasts, and antibacterial activity were evaluated to characterize tested biomaterials. The results showed that the addition of 1.75% gypsum and gentamicin caused short-term calcium ion compensation in media incubated with the composite. The combination of both additives also increased antibacterial activity against bacteria representative of bone infections without affecting osteoblast proliferation, hemocompatibility, and mechanical parameters. Thus, gypsum and antibiotic supplementation may provide advanced functionality for bone-regeneration materials based on hydroxyapatite of a high surface area and increasingly high Ca2+ sorption capacity.

Gypsum-related compensation of ions uptake by highly porous hydroxyapatite ceramics - Consequences for osteoblasts growth and proliferation.

Hydroxyapatites of high calcium and phosphate ions adsorption capacity are highly bioactive. However, they cause the removal of these ions from tissue liquids and cell culture media, thus reducing viability and proliferation potential of osteoblasts. Addition of small amount of gypsum (calcium sulfate dihydrate) to such hydroxyapatite-based composites may help to compensate the ions removal and stimulate the osteoblasts growth and proliferation. Therefore, the aim of this work was to enrich the highly porous hydroxyapatite-based composite with gypsum and verify its effect on ions adsorption as well as osteoblasts viability and proliferation. The results showed that addition of 1.5-1.75% gypsum caused short-term calcium ions compensation in media incubated with the composite and time-shifted increase of osteoblasts proliferation. Moreover, presence of gypsum in the composite increased the content of large pores in SBF-incubated biomaterials with no effect on their microstructure or mechanical parameters. Overall, gypsum addition improves the compatibility of hydroxyapatite-based materials with no critical disadvantages for other properties.

Metal TiO2 Nanotube Layers for the Treatment of Dental Implant Infections.

Titanium oxide nanotube layers with silver and zinc nanoparticles are attracting increasing attention in the design of bone and dental implants due to their antimicrobial potential and their ability to control host cell adhesion, growth, and differentiation. However, recent reports indicate that the etiology of dental infections is more complex than has been previously considered. Therefore, the antimicrobial potential of dental implants should be evaluated against at least several different microorganisms cooperating in human mouth colonization. In this study, Ag and Zn nanoparticles incorporated into titanium oxide nanotubular layers were studied with regard to how they affect Candida albicans, Candida parapsilosis, and Streptococcus mutans. Layers of titanium oxide nanotubes with an average diameter of 110 nm were fabricated by electrochemical anodization, annealed at 650 °C, and modified with approx. 5 wt % Ag or Zn nanoparticles. The surfaces were examined with the scanning electron microscopy-energy dispersive X-ray analysis, scanning transmission electron microscopy, and X-ray photoelectron spectroscopy techniques and subjected to evaluation of microbial-killing and microbial adhesion-inhibiting potency. In a 1.5 h long adhesion test, the samples were found more effective toward yeast strains than toward S. mutans. In a release-killing test, the microorganisms were almost completely eliminated by the samples, either within 3 h of contact (for S. mutans) or 24 h of contact (for both yeast strains). Although further improvement is advisable, it seems that Ag and Zn nanoparticles incorporated into TiO2 nanotubular surfaces provide a powerful tool for reducing the incidence of bone implant infections. Their high bidirectional activity (against both Candida species and S. mutans) makes the layers tested particularly promising for the design of dental implants.

Synthesis and in vitro antiproliferative and antibacterial activity of new thiazolidine-2,4-dione derivatives.

In our present research, we synthesised new thiazolidine-2,4-diones (12-28). All the newly synthesised compounds were evaluated for antiproliferative and antibacterial activity. Antiproliferative evaluation was carried out using normal human skin fibroblasts and tumour cell lines: A549, HepG2, and MCF-7. The IC50 values were determined for tested compounds revealing antiproliferative activity. Moreover, safety index (SI) was calculated. Among all tested derivatives, the compound 18 revealed the highest antiproliferative activity against human lung, breast, and liver cancer cells. More importantly, the derivative 18 showed meaningfully lower IC50 values when compared to the reference substance, irinotecan, and relatively high SI values. Moreover, newly synthesised compounds were screened for the bacteria growth inhibition in vitro. According to our screening results, most active compound was the derivative 18 against Gram-positive bacteria. Therefore, it may be implied that the novel compound 18 appears to be a very promising agent for anticancer treatment.

Do Ca2+-adsorbing ceramics reduce the release of calcium ions from gypsum-based biomaterials?

Bone implantable materials based on calcium sulfate dihydrate dissolve quickly in tissue liquids and release calcium ions at very high levels. This phenomenon induces temporary toxicity for osteoblasts, may cause local inflammation and delay the healing process. Reduction in the calcium ion release rate by gypsum could be therefore beneficial for the healing of gypsum-filled bone defects. The aim of this study concerned the potential use of calcium phosphate ceramics of various porosities for the reduction of high Ca(2+) ion release from gypsum-based materials. Highly porous ceramics failed to reduce the level of Ca(2+) ions released to the medium in a continuous flow system. However, it succeeded to shorten the period of high calcium level. It was not the phase composition but the high porosity of ceramics that was found crucial for both the shortening of the Ca(2+) release-related toxicity period and intensification of apatite deposition on the composite. Nonporous ceramics was completely ineffective for this purpose and did not show any ability to absorb calcium ions at a significant level. Moreover, according to our observations, complex studies imitating in vivo systems, rather than standard tests, are essential for the proper evaluation of implantable biomaterials.

Covalent coating of hydroxyapatite by keratin stabilizes gentamicin release.

A novel hybrid hydroxyapatite (HAP) matrix, covalently coated with rarely applied, hardly degradable keratin and effectively modified by gentamicin immobilized in mixed-type mode (via interactions of diverse strength), was created. This hybrid showed a remarkably high drug immobilization yield and the most sustainable antibiotic release among all tested composites. It was also able to inhibit bacterial growth, both in surrounding liquid and on matrix surface, much longer (for at least 121 days of experiment) than analogous gelatin-modified and nonmodified matrices. Gentamicin-keratin-coated-HAP granules were nontoxic to human osteoblasts and enabled their proliferation with a rate similar as noncoated HAP. Presence of keratin on HAP granules seemed to slightly enhance the osteoblast proliferation. The results indicate that newly created HAP hybrid with covalently immobilized keratin and gentamicin--nontoxic and osteoblast-friendly--is a promising biomaterial of significantly prolonged antibacterial activity.