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Host immune response induced by foreign bone biomaterials plays an important role in determining their fate after implantation. Hence, it is well worth designing advanced bone substitute materials with beneficial immunomodulatory properties to modulate the host-material interactions. Bioactive glasses (BG), with excellent osteoconductivity and osteoinductivity, are regarded as important biomaterials in the field of bone regeneration. In order to explore a novel BG-based osteoimmunomodulatory implant with the capacity of potentially enhancing bone regeneration, it is a possible way to regulate the local immune microenvironment through manipulating macrophage polarization. In this study, strontium-substituted submicrometer bioactive glass (Sr-SBG) was prepared as an osteoimmunomodulatory bone repair material. To investigate whether the incorporation of Sr into SBG could synergistically improve osteogenesis by altering macrophage response, we systematically evaluated the interaction between Sr-SBG and macrophage during the process of bone regeneration by in vitro biological evaluation and in vivo histological assessment. It was found that the Sr-SBG modulates proper inflammatory status, leading to enhanced osteogenesis of mouse mesenchymal stem cells (mMSCs) and suppressed osteoclastogenesis of RAW 264.7 cells compared to SBG without strontium substitution. In vivo study confirmed that Sr-SBG initiated a less severe immune response and had an improved effect on bone regeneration than SBG, which corresponded with the in vitro evaluation. In conclusion, these findings suggested that Sr-SBG could be a promising immunomodulatory bone repair material designed for improved bone regeneration.

We report on silver-gold core-shell nanostructures that contain Methylene Blue (MB) at the gold-silver interface. They can be used as reporter molecules in surfaceenhanced Raman scattering (SERS) labels. The labels are stable and have strong SERS activity. TEM imaging revealed that these nanoparticles display bright and dark stripe structures. In addition, these labels can act as probes that can be detected and imaged through the specific Raman signatures of the reporters. We show that such SERS probes can identify cellular structures due to enhanced Raman spectra of intrinsic cellular molecules measured in the local optical fields of the core-shell nanostructures. They also provide structural information on the cellular environment as demonstrated for these nanoparticles as new SERS-active and biocompatible substrates for imaging of live cells.

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As one of the prospective two-dimensional nanomaterials, black phosphorus (BP), which has excellent physical and chemical properties, has witnessed quick development in theranostic applications. The more recent advances in combining BP nanosheet (NS) with nanoparticles exhibit new opportunities to develop multifunctional nanocomposites. However, more effort should be devoted to elucidate the nanomaterial-cell interaction mechanism before the bio-applications of BP-nanoparticle hybrids. Herein, the intracellular behaviors of BP-gold nanoparticles (BP-Au NSs) are first investigated using the surface-enhanced Raman scattering (SERS) technique. The presence of Au nanoparticles on the surface of a BP sheet allows nanohybrids with excellent SERS activity to enhance the intrinsic Raman signals of cellular components located around the NSs. Data from an endocytosis inhibitor blocking assay reveal that the nanohybrids are mainly taken up by macropinocytosis and caveolae-dependent endocytosis, which are energy-dependent processes. Associated with colocalization experiments, nanohybrids are found to internalize into lysosomes and the endoplasmic reticulum. Moreover, the SERS difference spectrum is extracted after Raman-fluorescence colocalization statistical analysis to distinguish the molecular structural differences in the biochemical components of the two organelles. These findings supply a definite cellular mechanistic understanding of the nano-biointeractions of nanocomposites in cancer cells, which may be of great importance to the biomedical applications of nanotechnology in the future.