J. Funct. Biomater., Volume 15, Issue 5 (May 2024) – 8 articles

This study aims to develop multi-functional bio-safe dental resin composites with capabilities for mineralization, high in vitro biocompatibility, and anti-biofilm properties. To address this issue, experimental resin composites consisting of UDMA/TEGDMA-based dental resins and low quantities (1.9, 3.8, and 7.7 vol%) of 45S5 bioactive glass (BAG) particles were developed. To evaluate cellular responses of resin composites, MC3T3-E1 cells were (1) exposed to the original composites extracts, (2) cultured directly on the freshly cured resin composites, or (3) cultured on preconditioned composites that have been soaked in deionized water (DI water), a cell culture medium (MEM), or a simple HEPES-containing artificial remineralization promotion (SHARP) solution for 14 days. Cell adhesion, cell viability, and cell differentiation were, respectively, assessed. In addition, the anti-biofilm properties of BAG-loaded resin composites regarding bacterial viability, biofilm thickness, and biofilm morphology, were assessed for the first time. In vitro biological results demonstrated that cell metabolic activity and ALP expression were significantly diminished when subjected to composite extracts or direct contact with the resin composites containing BAG fillers. However, after the preconditioning treatments in MEM and SHARP solutions, the biomimetic calcium phosphate minerals on 7.7 vol% BAG-loaded composites revealed unimpaired or even better cellular processes, including cell adhesion, cell proliferation, and early cell differentiation. Furthermore, resin composites with 1.9, 3.8, and 7.7 vol% BAG could not only reduce cell viability in S. mutans biofilm on the composite surface but also reduce the biofilm thickness and bacterial aggregations. This phenomenon was more evident in BAG7.7 due to the high ionic osmotic pressure and alkaline microenvironment caused by BAG dissolution. This study concludes that multi-functional bio-safe resin composites with mineralization and anti-biofilm properties can be achieved by adding low quantities of BAG into the resin system, which offers promising abilities to mineralize as well as prevent caries without sacrificing biological activity. Full article

Objective: Dental hypersensitivity remains widespread, underscoring the need for materials that can effectively seal dental tubules. This study evaluated the potential of bioactive-glass-infused hydroxyethyl cellulose gels in this context. Methods: Five gels were synthesized, each containing 20% bioactive glass (specifically, 45S5, S53P4, Biomin F, and Biomin C), with an additional blank gel serving as a control. Subjected to two months of accelerated aging at 37 ± 2 °C, these gels were assessed for key properties: viscosity, water disintegration time, pH level, consistency, adhesion to glass, and element release capability. Results: Across the board, the gels facilitated the release of calcium, phosphate, and silicon ions, raising the pH from 9.00 ± 0.10 to 9.7 ± 0.0—a range conducive to remineralization. Dissolution in water occurred within 30–50 min post-application. Viscosity readings showed variability, with 45S5 reaching 6337 ± 24 mPa/s and Biomin F at 3269 ± 18 mPa/s after two months. Initial adhesion for the blank gel was measured at 0.27 ± 0.04 Pa, increasing to 0.73 ± 0.06 Pa for the others over time. Gels can release elements upon contact with water (Ca⁻ Biomin C 104.8 ± 15.7 mg/L; Na⁻ Biomin F 76.30 ± 11.44 mg/L; P⁻ Biomin C 2.623 ± 0.393 mg/L; Si⁻ 45S5-45.15 ± 6.77mg/L, F⁻ Biomin F⁻ 3.256 ± 0.651mg/L; Cl⁻ Biomin C 135.5 ± 20.3 mg/L after 45 min). Conclusions: These findings highlight the gels’ capacity to kickstart the remineralization process by delivering critical ions needed for enamel layer reconstruction. Further exploration in more dynamic, real-world conditions is recommended to fully ascertain their practical utility. Full article

Titanium continues to be the gold standard in the field of osteosynthesis materials. This also applies to pediatric craniofacial surgery. Various resorbable materials have already been developed in order to avoid costly and risky second operations to remove metal in children. However, none of these resorbable materials have been able to completely replace the previous gold standard, titanium, in a satisfactory manner. This has led to the need for a new resorbable osteosynthesis material that fulfills the requirements for biocompatibility, stability, and uniform resorption. In our previous in vitro and in vivo work, we were able to show that molybdenum fulfills these requirements. To further confirm these results, we conducted a proof of concept in four domestic pigs, each of which was implanted with a resorbable molybdenum implant. The animals were then examined daily for local inflammatory parameters. After 54 days, the animals were euthanized with subsequent computer tomography imaging. We also removed the implants together with the surrounding tissue and parts of the spleen, liver, and kidney for histopathological evaluation. The molybdenum implants were also analyzed metallographically and using scanning electron microscopy. A blood sample was taken pre- and post-operatively. None of the animals showed clinical signs of inflammation over the entire test period. Histopathologically, good tissue compatibility was found. Early signs of degradation were observed after 54 days, which were not sufficient for major resorption. Resorption is expected with longer in situ residence times based on results of similar earlier investigations. Full article

Cargo encapsulation through emulsion-based methods has been pondered over the years. Although several microemulsification techniques have been employed for the microcapsule’s synthesis, there are still no clear guidelines regarding the suitability of one technique over the others or the impacts on the morphological and physicochemical stability of the final particles. Therefore, in this systematic study, we investigated the influence of synthesis parameters on the fabrication of emulsion-based microcapsules concerning morphological and physicochemical properties. Using poly(urea-formaldehyde) (PUF) microcapsules as a model system, and after determining the optimal core/shell ratio, we tested three different microemulsification techniques (magnetic stirring, ultrasonication, and mechanical stirring) and two different cargo types (100% TEGDMA (Triethylene glycol dimethacrylate) and 80% TEGDMA + 20% DMAM (N,N-Dimethylacrylamide)). The resulting microcapsules were characterized via optical and scanning electron microscopies, followed by size distribution analysis. The encapsulation efficiency was obtained through the extraction method, and the percentage reaction yield was calculated. Physicochemical properties were assessed by incubating the microcapsules under different osmotic pressures for 1 day and 1, 2, or 4 weeks. The data were analyzed statistically with one-way ANOVA and Tukey’s tests (α = 0.05). Overall, the mechanical stirring resulted in the most homogeneous and stable microcapsules, with an increased reaction yield from 100% to 50% in comparison with ultrasonication and magnetic methods, respectively. The average microcapsule diameter ranged from 5 to 450 µm, with the smallest ones in the ultrasonication and the largest ones in the magnetic stirring groups. The water affinities of the encapsulated cargo influenced the microcapsule formation and stability, with the incorporation of DMAM leading to more homogeneous and stable microcapsules. Environmental osmotic pressure led to cargo loss or the selective swelling of the shells. In summary, this systematic investigation provides insights and highlights commonly overlooked factors that can influence microcapsule fabrication and guide the choice based on a diligent analysis of therapeutic niche requirements. Full article

The in vitro evaluation of 3D scaffolds for bone tissue engineering in mono-cultures is a common practice; however, it does not represent the native complex nature of bone tissue. Co-cultures of osteoblasts and osteoclasts, without the addition of stimulating agents for monitoring cellular cross-talk, remains a challenge. In this study, a growth factor-free co-culture of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and human peripheral blood mononuclear cells (hPBMCs) has been established and used for the evaluation of 3D-printed scaffolds for bone tissue engineering. The scaffolds were produced from PLLA/PCL/PHBV polymeric blends, with two composite materials produced through the addition of 2.5% w/v nanohydroxyapatite (nHA) or strontium-substituted nanohydroxyapatite (Sr-nHA). Cell morphology data showed that hPBMCs remained undifferentiated in co-culture, while no obvious differences were observed in the mono- and co-cultures of hBM-MSCs. A significantly increased alkaline phosphatase (ALP) activity and osteogenic gene expression was observed in co-culture on Sr-nHA-containing scaffolds. Tartrate-resistant acid phosphatase (TRAP) activity and osteoclastogenic gene expression displayed significantly suppressed levels in co-culture on Sr-nHA-containing scaffolds. Interestingly, mono-cultures of hPBMCs on Sr-nHA-containing scaffolds indicated a delay in osteoclasts formation, as evidenced from TRAP activity and gene expression, demonstrating that strontium acts as an osteoclastogenesis inhibitor. This co-culture study presents an effective 3D model to evaluate the regenerative capacity of scaffolds for bone tissue engineering, thus minimizing time-consuming and costly in vivo experiments. Full article

This study aimed to analyze the effect of the height of the proximal axial wall of the prepared tooth and the distance between the adjacent tooth and the prepared tooth on the scan accuracy of intraoral scanners. Ten working casts with maxillary first molars prepared to receive zirconia crowns were randomly obtained from a dental clinic. Each of the 10 casts was scanned using two intraoral scanners (i700; MEDIT and CS3600; Carestream; computer-aided design [CAD] test model, CTM; N = 15 per working cast) 15 times per scanner. Individual dies of the prepared teeth were fabricated, and high-precision scan data were acquired using a laboratory scanner (CAD reference model, CRM; N = 1). CTMs were aligned relative to the prepared tooth of CRMs by using three-dimensional inspection software (Ver 2018.1.0; Control X; 3D Systems). Data were statistically analyzed using an independent t-test and one-way analysis of variance for between-group comparisons (α = 0.05). The inaccuracy in the proximal regions (mesial or distal) of the prepared tooth was higher than that in the buccal and lingual regions (p < 0.05). The scan accuracy was not correlated with the variables when the distance between the adjacent tooth and the prepared tooth was ≥2.0 mm and the height of the proximal axial wall of the prepared tooth was <3.0 mm (p > 0.05). Therefore, an excellent scan accuracy can be obtained using an intraoral scanner when the distance between the adjacent tooth and the prepared tooth is ≥2.0 mm and the proximal axial wall height of the prepared tooth is <3.0 mm. Full article

Titanium with apatite-forming ability as well as antibacterial activity is useful as a component of antibacterial dental implants. When Ti was subjected to hydrogen peroxide (H₂O₂), copper acetate (Cu(OAc)₂), and heat (H₂O₂-Cu(OAc)₂-heat) treatments, a network structure of anatase and rutile titanium dioxide (TiO₂) and fine copper oxide (CuO) particles was formed on the Ti surface. The resulting samples accumulated a dense and uniform apatite layer on the surface when incubated in simulated body fluid and showed enhanced antibacterial activity against Escherichia coli and Staphylococcus aureus under visible-light irradiation. Electron spin resonance spectra of H₂O₂-Cu(OAc)₂-heat-treated samples showed that hydroxyl radicals (·OH) were generated from the samples, and the concentration of ·OH increased with increasing Cu concentration of the Cu(OAc)₂ solution. The enhanced antibacterial activity of these samples under visible-light irradiation may be attributable to the generation of ·OH from samples. These results suggest that Ti implants obtained using H₂O₂-Cu(OAc)₂-heat treatments and subjected to regular or on-demand visible-light irradiation may provide a decreased risk of peri-implantitis. Full article

This paper presents methods for developing high-performance interface electrode materials designed to enhance signal collection efficacy during long-term (over 24 h) electrocardiography (ECG) monitoring. The electrode materials are fabricated by integrating commercial ECG liquid hydrogels with carbon nanotubes (CNTs), which are widely utilized in dry-electrode technologies and extensively discussed in the current scientific literature. The composite materials are either prepared by dispersing CNTs within the commercial liquid hydrogel matrix or by encasing the hydrogels in macroscopic CNT films. Both approaches ensure the optimal wetting of the epidermis via the hydrogels, while the CNTs reduce material impedance and stabilize the drying process. The resulting electrode materials maintain their softness, allowing for micro-conformal skin attachment, and are biocompatible. Empirical testing confirms that the ECG electrodes employing these hybrid hydrogels adhere to relevant standards for durations exceeding 24 h. These innovative hybrid solutions merge the benefits of both wet and dry ECG electrode technologies, potentially facilitating the extended monitoring of ECG signals and thus advancing the diagnosis and treatment of various cardiac conditions. Full article