Research progress on the biological modifications of implant materials in 3D printed intervertebral fusion cages.

Anterior spine decompression and reconstruction with bone grafts and fusion is a routine spinal surgery. The intervertebral fusion cage can maintain intervertebral height and provide a bone graft window. Titanium fusion cages are the most widely used metal material in spinal clinical applications. However, there is a certain incidence of complications in clinical follow-ups, such as pseudoarticulation formation and implant displacement due to nonfusion of bone grafts in the cage. With the deepening research on metal materials, the properties of these materials have been developed from being biologically inert to having biological activity and biological functionalization, promoting adhesion, cell differentiation, and bone fusion. In addition, 3D printing, thin-film, active biological material, and 4D bioprinting technology are also being used in the biofunctionalization and intelligent advanced manufacturing processes of implant devices in the spine. This review focuses on the biofunctionalization of implant materials in 3D printed intervertebral fusion cages. The surface modifications of implant materials in metal endoscopy, material biocompatibility, and bioactive functionalizationare summarized. Furthermore, the prospects and challenges of the biofunctionalization of implant materials in spinal surgery are discussed. Fig.a.b.c.d.e.f.g As a pre-selected image for the cover, I really look forward to being selected. Special thanks to you for your comments.

RUNX3 derived hsa_circ_0005752 accelerates the osteogenic differentiation of adipose-derived stem cells via the miR-496/MDM2-p53 pathway.

BACKGROUND: Circular RNAs (circRNAs) are non-coding RNAs that play a pivotal role in bone diseases. RUNX3 was an essential transcriptional regulator during osteogenesis. However, it is unknown whether RUNX3 regulates hsa_circ_0005752 during osteogenic differentiation. METHODS: The levels of hsa_circ_0005752 and RUNX3 were measured by qRT-PCR after osteogenic differentiation of ADSCs. The osteogenic differentiation was analyzed by Alkaline phosphatase (ALP) staining and Alizarin red staining (ARS). qRT-PCR and western blot were used to assess the expressions of osteogenic differentiation-related molecules. RNA pull-down, RIP, and luciferase reporter assays determine the interactions between miR-496 and hsa_circ_0005752 or MDM2 mRNA. CHIP-PCR analyzed the interaction between RUNX3 and LPAR1. Finally, the potential roles of RUNX3 were investigated during osteogenic differentiation with or without hsa_circ_0005752 knockdown. RESULTS: Hsa_circ_0005752 and RUNX3 were significantly increased, and miR-496 was remarkably decreased in ADSCs after osteogenic differentiation. Hsa_circ_0005752 could promote osteogenic differentiation, as shown by enhancing ALP and ARS staining intensity. Hsa_circ_0005752 enhanced the expressions of Runx2, ALP, Osx, and OCN. Furthermore, hsa_circ_0005752 directly targeted miR-496, which can directly bind to MDM2. RUNX3 bound to the LPAR1 promoter and enhanced hsa_circ_0005752 expressions. Moreover, the enhanced expression of hsa_circ_0005752 by RUNX3 could promote osteogenic differentiation, whereas knockdown of hsa_circ_0005752 partially antagonized the effects of RUNX3. CONCLUSION: Our study demonstrated that RUNX3 promoted osteogenic differentiation via regulating the hsa_circ_0005752/miR-496/MDM2 axis and thus provided a new therapeutic strategy for osteoporosis.