Black-Phosphorus-Nanosheet-Reinforced Coating of Implants for Sequential Biofilm Ablation and Bone Fracture Healing Acceleration.

Incurable implant-related infection may cause catastrophic consequences due to the existence of a biofilm that resists the infiltration of host immune cells and antibiotics. Innovative approaches inspired by nanomedicine, e.g., engineering innovative multifunctional bionic coating systems on the surface of implants, are becoming increasingly attractive. Herein, 2D black phosphorus nanosheets (BPs) were loaded onto a hydroxyapatite (HA)-coated metal implant to construct a BPs@HA composite coating. With its photothermal conversion effect and in situ biomineralization, the BPs@HA coating shows excellent performances in ablating the bacterial biofilm and accelerating fracture healing, which were verified through both in vitro and in vivo studies. Moreover, differentially expressed genes of bone formation and bone mesenchymal stem cells (BMSCs) regulated by the BPs@HA coating were identified using absolute quantitative transcriptome sequencing followed by the screening of gene differential expressions. A functional enrichment analysis reveals that the expression of core markers related to BMSC differentiation and bone formation could be effectively regulated by BPs through a metabolism-related pathway. This work not only illustrates the great potential in clinical application of the BPs@HA composite coating to eliminate bacteria and accelerate bone fracture healing but also contributes to an understanding of the underlying molecular mechanism of osteogenesis physiological function regulation based on an analysis of absolute quantitative transcriptome sequencing.

Dual targeting curcumin loaded alendronate-hyaluronan- octadecanoic acid micelles for improving osteosarcoma therapy.

INTRODUCTION: Curcumin (CUR) is a general ingredient of traditional Chinese medicine, which has potential antitumor effects. However, its use clinically has been limited due to its low aqueous solubility and bioavailability. In order to improve the therapeutic effect of CUR on osteosarcoma (i.e., bone cancer), a multifunctional micelle was developed here by combining active bone accumulating ability with tumor CD44 targeting capacity. METHODS: The CUR loaded micelles were self-assembled by using alendronate-hyaluronic acid-octadecanoic acid (ALN-HA-C18) as an amphiphilic material. The obtained micelles were characterized for size and drug loading. In addition, the in vitro release behavior of CUR was investigated under PBS (pH 5.7) medium containing 1% Tween 80 at 37℃. Furthermore, an hydroxyapatite (the major inorganic component of bone) affinity experiment was studied. In vitro antitumor activity was evaluated. Finally, the anti-tumor efficiency was studied. RESULTS: The size and drug loading of the CUR loaded ALN-HA-C18 micelles were about 118 ± 3.6 nm and 6 ± 1.2%, respectively. CUR was released from the ALN-HA-C18 micelles in a sustained manner after 12 h. The hydroxyapatite affinity experiment indicated that CUR loaded ALN-HA-C18 micelles exhibited a high affinity to bone. CUR loaded ALN-HA-C18 micelles exhibited much higher cytotoxic activity against MG-63 cells compared to free CUR. Finally, CUR loaded ALN-HA-C18 micelles effectively delayed anti-tumor growth properties in osteosarcoma bearing mice as compared with free CUR. CONCLUSION: The present study suggested that ALN-HA-C18 is a novel promising micelle for osteosarcoma targeting and delivery of the hydrophobic anticancer drug CUR.

Effect of needle diameter, type and volume of contrast agent on intervertebral disc degeneration in rats with discography.

PURPOSE: Discography can increase disc degeneration, but the influence of different discography variables on the degeneration of discs has not been reported. The aim of this study was to investigate the effects of discography variables of needle diameter, type of contrast agent and volume of contrast agent on disc degeneration. METHODS: Three separate experiments examined needle diameter, and type and volume of contrast agent. Coccygeal discs (Co7-10) adult male rats were used. X-rays were used to detect the disc height degeneration index at 1, 2 and 4 weeks after the procedure. MRI was used to study the changes in the disc structure and the signal intensity of IVD 2 and 4 weeks after the procedure. Disc water content and histology were measured at 4 weeks after the procedure. RESULTS: A 21-g needle significantly increased disc degeneration when compared with the 30-g needle as detected by X-ray, MRI, disc water content and histology (P < 0.05). Two microlitres of iodine significantly decreased the disc MRI signal and water content at 4 weeks compared with the same volume of normal saline (P < 0.05). Three microlitres of iodine significantly increased disc degeneration when compared with 2 µl iodine, as detected by X-ray, MRI, disc water content and histology at 4 weeks (P < 0.05). CONCLUSION: To reduce disc degeneration after discography, it may be best to choose a smaller needle size, minimize the use of contrast agent and use non-ionic contrast agents with osmotic pressure similar to the intervertebral disc. These slides can be retrieved under Electronic Supplementary Material.