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Dicalcium silicate (Ca2SiO4, C2S) has osteogenic potential but induces macrophagic inflammation. Mitochondrial function plays a vital role in macrophage polarization and macrophagic inflammation. The mitochondrial function of C2S-treated macrophages is still unclear. This study hypothesized: (i) the C2S modulates mitochondrial function and autophagy in macrophages to regulate macrophagic inflammation, and (ii) C2S-induced macrophagic inflammation regulates osteogenesis. We used RAW264.7 cells as a model of macrophage. The C2S (75–150 μg/ml) extract was used to analyze the macrophagic mitochondrial function and macrophage-mediated effect on osteogenic differentiation of mouse bone marrow-derived mesenchymal stem cells (BMSCs). The results showed that C2S extract (150 μg/ml) induced TNF-α, IL-1β and IL-6 production in macrophages. C2S extract (150 μg/ml) enhanced reactive oxygen species level and intracellular calcium level but reduced mitochondrial membrane potential and ATP production. TEM images showed reduced mitochondrial abundance and altered the mitochondrial morphology in C2S (150 μg/ml)-treated macrophages. Protein level expression of PINK1, Parkin, Beclin1 and LC3 was upregulated but TOMM20 was downregulated. mRNA sequencing and KEGG analysis showed that C2S-induced differentially expressed mRNAs in macrophages were mainly distributed in the essential signaling pathways involved in mitochondrial function and autophagy. The conditioned medium from C2S-treated macrophage robustly promoted osteogenic differentiation in BMSCs. In conclusion, our results indicate mitochondrial dysfunction and autophagy as the possible mechanism of C2S-induced macrophagic inflammation. The promotion of osteogenic differentiation of BMSCs by the C2S-induced macrophagic inflammation suggests the potential application of C2S in developing immunomodulatory bone grafts.

Bone grafts or prosthetic implant designing for clinical application is challenging due to the complexity of integrated physiological processes. The revolutionary advances of nanotechnology in the biomaterial field expedite and endorse the current unresolved complexity in functional bone graft and implant design. Rare earth (RE) materials are emerging biomaterials in tissue engineering due to their unique biocompatibility, fluorescence upconversion, antimicrobial, antioxidants, and anti‐inflammatory properties. Researchers have developed various RE smart nano‐biomaterials for bone tissue engineering and implantology applications in the past two decades. Furthermore, researchers have explored the molecular mechanisms of RE material‐mediated tissue regeneration. Recent advances in biomedical applications of micro or nano‐scale RE materials have provided a foundation for developing novel, cost‐effective bone tissue engineering strategies. This review attempted to provide an overview of RE nanomaterials' technological innovations in bone tissue engineering and implantology and summarized the osteogenic, angiogenic, immunomodulatory, antioxidant, in vivo bone tissue imaging, and antimicrobial properties of various RE nanomaterials, as well as the molecular mechanisms involved in these biological events. Further, we extend to discuss the challenges and prospects of RE smart nano‐biomaterials in the field of bone tissue engineering and implantology.

The effective wound management strategies depends on identification and manipulation of the molecular defects in the pathophysiology of wound. Poor vascularization, protease susceptibility and microbial invasion at wound site affect the early wound closure. Hence, an efficient wound dressing material needs to promote angiogenesis, control proteolytic activity and microbial attack. The present study, describes designing and developing a novel wound dressing material by stabilization of collagen with juglone functionalized silver nanoparticle. Stabilization of collagen with juglone functionalized silver nanoparticles enhanced thermal properties, influenced the uniform alignment of collagen fibrils which enhanced collagen's ability to promote cell proliferation. FTIR and CD analyses revealed that juglone functionalized silver nanoparticles did not induced any structural changes in the collagen molecule. Juglone functionalized silver nanoparticles controlled the proteolytic activity in a spatio-temporal manner and elicited the angiogenic response by upregulation of cell adhesion molecules like β catenin and VE cadherin which had promoted the cell attachment and cell-cell contact. It had also promoted the expression of angiogenic signaling molecules like VEGF and VEGFR2. Further, the in vivo studies proved that the juglone functionalized silver nanoparticles had a potential role in rapid wound closure due to the cumulative property of juglone and silver nanoparticles.

In the present investigation, we report the surface activity, micellar, thermodynamic properties and bioactivity studies of synthesized counterion coupled (COCO) gemini surfactant, 1,6-bis(N,N-hexadecyldimethylammonium) adipate (16-6-16). In aqueous solution, the CMC (critical micelle concentration) of 16-6-16 was measured by electrical conductivity, surface tension, dye solubilization and fluorescence measurements techniques. The surface activities and surface properties of the COCO gemini surfactant, 16-6-16 were evaluated. The CMC as well as Amin (the minimum area per surfactant molecule at the air/water interface) decrease and the Γmax (the maximum surface excess concentration at the air/water interface) increases with increasing the temperature. We also report the thermodynamics of 16-6-16 and evaluated Gibbs energies. The aggregation number (Nagg) of 16-6-16 is reported. The bioactivity studies of 16-6-16 showed to be nontoxic, biocompatible and having good antibacterial activity.

Uniform nanocrystalline LaVO4: Eu nanorods have been successfully prepared through a simple solution based hydrothermal process using catechin hydrate as a ligand. Thermogravimetric, CHN, and zeta potential analysis confirmed the coating of catechin hydrate on the surface of LaVO4. The use of Eu3+ ions resulted in a red luminescence of the products, with an emission maximum at 618 nm. Laser flash photolysis of these luminescent nanorods demonstrated a photoluminescent decay time of milliseconds. In vitro assays performed with HaCaT cells validated the feasibility of these nanorods to serve as nuclear nano bioprobe. Nanorods emission was observed in the cells by confocal microscopy. In addition, red emitter nanorods displayed no cytotoxicity over a wide concentration ranging namely 10 μg–500 μg by MTT cell viability assay. These results suggest that LaVO4: Eu nanorods possess the potential to serve as a luminescent probe in bioimaging and nuclear targeting applications.

A novel approach on incorporation of divalent species such as Mg, Ca and Sr into the titania nanostructures formed on Ti metal surface and their comparative study on enhancement of bioactivity, protein adsorption and cell compatibility is reported. When treated with hydrogen peroxide, Ti metal forms hydrogen titanate. On subsequent treatment with Mg or Ca or Sr nitrate solutions, respective ions are incorporated into hydrogen titanate layer, and heat treatment leads to titania decorated with these ions. The resultant heat-treated samples when soaked in simulated body fluid form bone-like apatite which indicates the present surface modification enhances the bioactivity. Further, enhanced protein adsorption in bovine serum albumin is an indication of suitability of these divalent species to form chelate compounds with amino acids, and Ca containing titania nanostructure favours more protein adsorption compared to the others. Cytocompatibility studies using MG-63, human osteosarcoma cell lines shows these divalent ion containing titania nanostructure favours the cell attachment and did not show any cytotoxicity. Bioactivity, enhanced protein adsorption along with cytocompatibility clearly indicates such surface modification approach to be useful to design hard tissue replacement materials in orthopaedic and dental field.

Titanium–6 aluminium–4 vanadium (Ti64) alloy was modified to a hydrophilic, cytocompatible, antibacterial and bioactive surface via a simple cost effective chemical treatment method. A fine porous network structure of sodium hydrogen titanate (SHT) was formed on the Ti64 alloy surface by using sodium hydroxide treatment. The incorporated Na+ ions are replaced by Ag+ ions by a subsequent silver nitrate treatment. Contact angle measurement indicated that the silver containing Ti64 alloy surface is hydrophilic at lower silver concentration. The antibacterial study of the thus prepared sample against Staphylococcus aureus confirmed the bacterial resistance of the Ti64 alloy. As evident from the AAS result, the sustained release of Ag into the culture medium results in antibacterial activity. Cytocompatibility studies on MG63 cell lines showed above 80% cell viability and also good cell attachment. This confirmed the nontoxic behavior of the present optimized silver concentration on the Ti64 surface for MG63 cells. In vitro bioactivity of the silver containing Ti64 sample in simulated body fluid showed bone-like apatite formation and the apatite-forming ability is not affected by Ag concentration or by heat treatment. Taken together, this surface modification study adds further information to our knowledge on the development of a bioactive Ti64 alloy with hydrophilicity, antibacterial activity and biocompatibility that may have considerable potential application as orthopedic and dental implants.

In the present study, the pH dependence hydroxyapatite (HAp) ceramics synthesis, and, their phase stabilities with respect to calcination temperatures were examined. Subsequently, HAp ceramics mixed with different silver amounts (HAp–Ag composites) were prepared in the temperature range 800–1200 °C to evaluate the phase stability of HAp in presence of silver. XRD results showed that as-synthesized HAp powder to be partially crystalline and are independent of pH of solution in the range of 9–11. These HAp phases remained stable even upto 1200 °C although crystallinity increased in all cases. Additional Ag peaks were appeared in HAp–Ag composites when the mixed powders were heated in the temperature range 800–1200 °C. FTIR result further confirmed the presence of Ca 2+ and PO 4 3− ions. TEM observation showed the precipitation of needle like HAp nanocrystals of 20–40 nm in length which agglomerated into particulate morphology above 800 °C. Antibacterial study of HAp–Ag composites on Staphylococcus aureus for 1, 3 and 5 wt% silver concentration showed that 3 wt% silver is sufficient to kill the surrounding bacteria. Further studies on NIH3T3 cells for HAp–Ag composites at 10 wt% silver of different concentrations showed good cytocompatibility compared to HAp indicates the prospective applications in therapeutic interventions.