Titanium (Ti) and its alloys offer favorable biocompatibility, mechanical properties and corrosion resistance, which makes them an ideal material choice for dental implants. However, the long-term success of Ti-based dental implants may be challenged due to implant-related infections and inadequate osseointegration. With the development of nanotechnology, nanoscale modifications and the application of nanomaterials have become key areas of focus for research on dental implants. Surface modifications and the use of various coatings, as well as the development of the controlled release of antibiotics or proteins, have improved the osseointegration and soft-tissue integration of dental implants, as well as their antibacterial and immunomodulatory functions. This review introduces recent nano-engineering technologies and materials used in topographical modifications and surface coatings of Ti-based dental implants. These advances are discussed and detailed, including an evaluation of the evidence of their biocompatibility, toxicity, antimicrobial activities and in-vivo performances. The comparison between these attempts at nano-engineering reveals that there are still research gaps that must be addressed towards their clinical translation. For instance, customized three-dimensional printing technology and stimuli-responsive, multi-functional and time-programmable implant surfaces holds great promise to advance this field. Furthermore, long-term in vivo studies under physiological conditions are required to ensure the clinical application of nanomaterial-modified dental implants.

Dental Implant Nano-Engineering: Advances, Limitations and Future Directions

Purpose Zinc (Zn), an essential trace element in the body, has stable chemical properties, excellent osteogenic ability and moderate immunomodulatory property. In the present study, a Zn-incorporated TiO2 nanotube (TNT) was fabricated on titanium (Ti) implant material. We aimed to evaluate the influence of nano-scale topography and Zn on behaviors of murine RAW 264.7 macrophages. Moreover, the effects of Zn-incorporated TNT surface-regulated macrophages on the behaviors and osteogenic differentiation of murine MC3T3-E1 osteoblasts were also investigated. Methods TNT coatings were firstly fabricated on a pure Ti surface using anodic oxidation, and then nano-scale Zn particles were incorporated onto TNTs by the hydrothermal method. Surface topography, chemical composition, roughness, hydrophilicity, Zn release pattern and protein adsorption ability of the Zn-incorporated TiO2 nanotube surface were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), surface profiler, contact angle test, Zn release test and protein adsorption test. The cell behaviors and both pro-inflammatory (M1) and pro-regenerative (M2) marker gene and protein levels in macrophages cultured on Zn-incorporated TNTs surfaces with different TNT diameters were detected. The supernatants of macrophages were extracted and preserved as conditioned medium (CM). Furthermore, the behaviors and osteogenic properties of osteoblasts cultured in CM on various surfaces were evaluated. Results The release profile of Zn on Zn-incorporated TNT surfaces revealed a controlled release pattern. Macrophages cultured on Zn-incorporated TNT surfaces displayed enhanced gene and protein expression of M2 markers, and M1 markers were moderately inhibited, compared with the LPS group (the inflammation model). When cultured in CM, osteoblasts cultured on Zn-incorporated TNTs showed strengthened cell proliferation, adhesion, osteogenesis-related gene expression, alkaline phosphatase activity and extracellular mineralization, compared with their TNT counterparts and the Ti group. Conclusion This study suggests that the application of Zn-incorporated TNT surfaces may establish an osteogenic microenvironment and accelerate bone formation. It provided a promising strategy of Ti surface modification for a better applicable prospect.

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Zn-Incorporated TiO2 Nanotube Surface Improves Osteogenesis Ability Through Influencing Immunomodulatory Function of Macrophages.

Dual-functional polyetheretherketone surface modification for regulating immunity and bone metabolism

In recent years, titanium(IV) dioxide nanoparticles (TiO2NPs) have shown promising potential in various biological applications such as antimicrobials, drug delivery, photodynamic therapy, biosensors, and tissue engineering. For employing TiO2NPs in these fields, their nanosurface must be coated or conjugated with organic and/or inorganic agents. This modification can improve their stability, photochemical properties, biocompatibility, and even surface area for further conjugation with other molecules such as drugs, targeting molecules, polymers, etc. This review describes the organic-based modification of TiO2NPs and their potential applications in the mentioned biological fields. In the first part of this review, around 75 recent publications (2017-2022) are mentioned on the common TiO2NP modifiers including organosilanes, polymers, small molecules, and hydrogels, which improve the photochemical features of TiO2NPs. In the second part of this review, we presented 149 recent papers (2020-2022) about the use of modified TiO2NPs in biological applications, in which specific bioactive modifiers are introduced in this part with their advantages. In this review, the following information is presented: (1) the common organic modifiers for TiO2NPs, (2) biologically important modifiers and their benefits, and (3) recent publications on biological studies on the modified TiO2NPs with their achievements. This review shows the paramount significance of the organic-based modification of TiO2NPs to enhance their biological effectiveness, paving the way toward the development of advanced TiO2-based nanomaterials in nanomedicine.

Surface modification of TiO2 nanoparticles with organic molecules and their biological applications.

Deep Candida albicans infection is one of the major causes of death in immunosuppressed hosts. Remodeling macrophages to phenotype M1 can decrease fungus burden and facilitate combating C. albicans under an immunosuppressive state. In this study, a nanotrinity was exploited to direct fungicidal macrophage polarization by leveraging the regulation pathways in macrophage redifferentiation. Conventional chemotherapeutic imatinib, which can abrogate M2 macrophage polarization via "shutting off" the STAT6 phosphorylation pathway, was encapsulated in biodegradable polymeric nanoparticles. In house-customized dual functional mannosylated chitosan oligosaccharides were then coated on the surface of the imatinib-laden nanoparticles, and thus, a mannosylated nanotrinity was achieved with ternary functions for macrophage remodeling: (i) imatinib-blocked STAT6 phosphorylation pathway for decreasing M2 macrophage population; (ii) chitosan oligosaccharides-mediated TLR-4 pathway activation that could promote macrophage redifferentiation to M1 phenotype; (iii) mannose motif-enhanced macrophage targeting. After physiochemical characterization, regulatory effects of the mannosylated nanotrinity on macrophages and the anti-C. albicans efficacy were evaluated at the cellular level and animal level, respectively. The results demonstrated that our mannosylated nanotrinity could efficiently induce macrophage polarization toward the M1 phenotype, decrease M2 phenotype production, and markedly lessen fungus burden and increased the median survival time of mice infected with C. albicans. Therefore, the mannosylated nanotrinity developed in this study could significantly induce macrophage remodeling in situ by the two-pronged process, "turning on" M1 phenotype polarization meanwhile "shutting off" M2 phenotype polarization, and thus allowed to eradicate C. albicans infection.

In Situ Mannosylated Nanotrinity-Mediated Macrophage Remodeling Combats Candida albicans Infection

Alginate/chitosan multilayer films coated on IL-4-loaded TiO2 nanotubes for modulation of macrophage phenotype

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Alginate/chitosan multilayer films coated on IL-4-loaded TiO2 nanotubes for modulation of macrophage phenotype