Gallium-containing mesoporous nanoparticles influence in-vitro osteogenic and osteoclastic activity.

Mesoporous silica nanoparticles were synthesized using a microemulsion-assisted sol-gel method, and calcium, gallium or a combination of both, were used as dopants. The influence of these metallic ions on the physicochemical properties of the nanoparticles was investigated by scanning and transmission electron microscopy, as well as N2 adsorption-desorption methods. The presence of calcium had a significant impact on the morphology and textural features of the nanoparticles. The addition of calcium increased the average diameter of the nanoparticles from 80 nm to 150 nm, while decreasing their specific surface area from 972 m2/g to 344 m2/g. The nanoparticles of all compositions were spheroidal, with a disordered mesoporous structure. An ion release study in cell culture medium demonstrated that gallium was released from the nanoparticles in a sustained manner. In direct contact with concentrations of up to 100 µg/mL of the nanoparticles, gallium-containing nanoparticles did not exhibit cytotoxicity towards pre-osteoblast MC3T3-E1 cells. Moreover, in vitro cell culture tests revealed that the addition of gallium to the nanoparticles enhanced osteogenic activity. Simultaneously, the nanoparticles disrupted the osteoclast differentiation of RAW 264.7 macrophage cells. These findings suggest that gallium-containing nanoparticles possess favorable physicochemical properties and biological characteristics, making them promising candidates for applications in bone tissue regeneration, particularly for unphysiological or pathological conditions such as osteoporosis.

Tailorable mechanical and degradation properties of KCl-reticulated and BDDE-crosslinked PCL/chitosan/κ-carrageenan electrospun fibers for biomedical applications: Effect of the crosslinking-reticulation synergy.

The development of intricated and interconnected porous mats is desired for many applications in biomedicine and other relevant fields. The mats that comprise the use of natural, bioactive, and biodegradable polymers are the focus of current research activities. In the present work, crosslinked fibers with improved characteristics were produced by incorporating 1,4-butanediol diglycidyl ether (BDDE) into a polymer formulation containing polycaprolactone (PCL), chitosan (CS), and κappa-carrageenan (κ-C). A slight variation of formic acid (FA)/acetic acid (AA) ratio used as a solvent system, significantly affected the characteristics of the produced fiber mats. Both polysaccharides and BDDE played a major role in tailoring mechanical properties when fibrous scaffolds were reticulated under KCl-mediated basic conditions for determined periods of time at 50 °C. In vitro biological assessment of the electrospun fiber mats revealed proliferation of MC3T3-E1 cells when incubated for 1 and 7 days. After staining the cells with 4',6-diamidino-2-phenylindole (DAPI)/rhodamine phalloidin an autofluorescence response was observed by fluorescence microscopy in the scaffold manufactured using a solvent with higher FA/AA ratio due to the formation of microfibers. The results demonstrated the potential of the BDDE-crosslinked PCL/CS/κ-C electrospun fibers as promising materials for biomedical applications that may include soft and bone tissue regeneration.

Zinc improves antibacterial, anti-inflammatory and cell motility activity of chitosan for wound healing applications.

We report the successful preparation and characterization of chitosan-Zn complex (ChiZn) in the form of films, intended to enhance the biological performance of chitosan by the presence of Zn as antibacterial agent and biologically active ion. The influence of Zn chelation on morphology and structure of chitosan was assessed by scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy and infrared spectroscopy. The biodegradability study of ChiZn showed a sustained release of Zn up to 2 mg/mL. No toxic response was observed toward stromal cell line ST-2 in indirect contact with the ChiZn films. The dissolution product of ChiZn showed improved wound closure (88% closure) compared to the positive control group (70% closure). Moreover, ChiZn exhibited antibacterial activity against S. aureus together with a slight increase (~30%) in the secretion of VEGF and moderate decrease in nitric oxide evolution. Our findings indicate that ChiZn could be used as a safe and effective wound healing agent.

Gallium containing bioactive materials: A review of anticancer, antibacterial, and osteogenic properties.

The incorporation of gallium into bioactive materials has been reported to enhance osteogenesis, to influence blood clotting, and to induce anti-cancer and anti-bacterial activity. Gallium-doped biomaterials prepared by various techniques include melt-derived and sol-gel-derived bioactive glasses, calcium phosphate bioceramics, metals and coatings. In this review, we summarize the recently reported developments in antibacterial, anticancer, osteogenesis, and hemostasis properties of Ga-doped biomaterials and briefly outline the mechanisms leading to Ga biological effects. The key finding is that gallium addition to biomaterials has great potential for treating bone-related diseases since it can be efficiently transferred to the desired region at a controllable rate. Besides, it can be used as a potential substitute for antibiotics for the inhibition of infections during the initial and advanced phases of the wound healing process. Ga is also used as an anticancer agent due to the increased concentration of gallium around excessive cell proliferation (tumor) sites. Moreover, we highlight the possibility to design different therapeutic approaches aimed at increasing the efficiency of the use of gallium containing bioactive materials for multifunctional applications.

Combination of Selective Etching and Impregnation toward Hollow Mesoporous Bioactive Glass Nanoparticles.

In this study, binary SiO2-CaO hollow mesoporous bioactive glass nanoparticles (HMBGNs) are prepared by combing selective etching and impregnation strategies. Spherical silica particles (SiO2 NPs) are used as hard cores to assemble cetyltrimethylammonium bromide (CTAB)/silica shells, which are later removed by selective etching to generate a hollow structure. After the removal of CTAB by calcination, the mesoporous shell of particles is formed. Calcium (Ca) is incorporated into the particles using impregnation by soaking the etched SiO2 NPs in calcium nitrate aqueous solution. The amount of incorporated Ca is tailorable by controlling the ratio of SiO2 NPs:calcium nitrate in the soaking solution. The produced HMBGNs are bioactive, as indicated by the rapid formation of hydroxyapatite on their surfaces after immersion in simulated body fluid. In a direct culture with MC3T3-E1 cells, HMBGNs were shown to exhibit concentration-dependent cytotoxicity and can stimulate osteogenic differentiation of MC3T3-E1 cells at concentrations of 1, 0.5, and 0.25 mg/mL. Our results indicate that the combination of selective etching and impregnation is a feasible approach to produce hierarchical HMBGNs. The produced hollow particles have potential in drug delivery and bone tissue regeneration applications, and should be further investigated in detailed in vitro and in vivo studies.

Cerium and gallium containing mesoporous bioactive glass nanoparticles for bone regeneration: Bioactivity, biocompatibility and antibacterial activity.

In recent years, mesoporous bioactive glass nanoparticles (MBGNPs) have generated great attention in biomedical applications. In this study, cerium and gallium doped MBGNPs were prepared by microemulsion assisted sol-gel method in the binary SiO2-CaO system. MBGNPs with spheroidal and pineal shaped morphology were obtained. Nitrogen sorption analysis elucidated the mesoporous structure of synthesized nanoparticles with high specific surface area. X-ray diffraction analysis confirmed the amorphous nature of the nanoparticles. The chemical compositions of all samples were determined by inductively coupled plasma-optical emission spectrometry (ICP-OES), which revealed that the contents of cerium and gallium could be tailored by adjusting the concentrations of the precursors used for the synthesis. All MBGNPs exhibited in vitro bioactivity when immersed in simulated body fluid, except the particles doped with higher amounts than 1 mol% of cerium. MBGNPs showed antibacterial activity against S. aureus and E. coli without exhibiting cytotoxicity towards MG-63 osteoblast-like cells. Mentioned features of the obtained Ce and Ga-doped MBGNPs make them useful for multifunctional applications such as drug delivery carriers or bioactive fillers for bone tissue engineering applications.

Polymeric Hydrogel Systems as Emerging Biomaterial Platforms to Enable Hemostasis and Wound Healing.

Broad interest in developing new hemostatic technologies arises from unmet needs in mitigating uncontrolled hemorrhage in emergency, surgical, and battlefield settings. Although a variety of hemostats, sealants, and adhesives are available, development of ideal hemostatic compositions that offer a range of remarkable properties including capability to effectively and immediately manage bleeding, excellent mechanical properties, biocompatibility, biodegradability, antibacterial effect, and strong tissue adhesion properties, under wet and dynamic conditions, still remains a challenge. Benefiting from tunable mechanical properties, high porosity, biocompatibility, injectability and ease of handling, polymeric hydrogels with outstanding hemostatic properties have been receiving increasing attention over the past several years. In this review, after shedding light on hemostasis and wound healing processes, the most recent progresses in hydrogel systems engineered from natural and synthetic polymers for hemostatic applications are discussed based on a comprehensive literature review. Most studies described used in vivo models with accessible and compressible wounds to assess the hemostatic performance of hydrogels. The challenges that need to be tackled to accelerate the translation of these novel hemostatic hydrogel systems to clinical practice are emphasized and future directions for research in the field are presented.