Osteogenesis or Apoptosis-Twofold Effects of Zn2+ on Bone Marrow Mesenchymal Stem Cells: An In Vitro and In Vivo Study.

Zinc (Zn) is a bioabsorbable metal that shows great potential as an implant material for orthopedic applications. Suitable concentrations of zinc ions promote osteogenesis, while excess zinc ions cause apoptosis. As a result, the conflicting impacts of Zn2+ concentration on osteogenesis could prove to be significant problems for the creation of novel materials. This study thoroughly examined the cell viability, proliferation, and osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) cultured in various concentrations of Zn2+ in vitro and validated the osteogenesis effects of zinc implantation in vivo. The effective promotion of cell survival, proliferation, migration, and osteogenic differentiation of bone marrow mesenchymal stem cell (BMSCs) may be achieved at a low concentration of Zn2+ (125 µM). The excessively high concentration of zinc ions (>250 µM) not only reduces BMSCs' viability and proliferation but also causes them to suffer apoptosis due to the disturbed zinc homeostasis and excessive Zn2+. Moreover, transcriptome sequencing was used to examine the underlying mechanisms of zinc-induced osteogenic differentiation with particular attention paid to the PI3K-AKT and TGF-ß pathways. The present investigation elucidated the dual impacts of Zn2+ microenvironments on the osteogenic characteristics of rBMSCs and the associated processes and might offer significant insights for refining the blueprint for zinc-based biomaterials.

A pH-neutral bioactive glass empowered gelatin-chitosan-sodium phytate composite scaffold for skull defect repair.

The ideal skull defect repairing material should have good biocompatibility and mechanical properties, and contribute to osteogenesis. In this study, we designed and fabricated biodegradable, bioactive and mechanically robust porous scaffolds composed completely of biological materials. We used a gelatin-chitosan blend as the matrix, sodium phytate instead of toxic glutaraldehyde for cross-linking, and the pH-neutral bioactive glass (PSC) to improve biological activity and mechanical properties. The chitosan-gelatin-30%PSC/sodium phytate composite scaffold avoided the problems of high toxicity in conventional cross-linking agents with glutaraldehyde, the poor mechanical support of the pure chitosan or gelatin scaffold, and the mismatch of the degradation rate with bone repair, becoming a promising new candidate for skull defect repair.

Injectable and Cell-Laden Hydrogel in the Contained Bone Defect Animal Model: A Systematic Review.

BACKGROUND: Due to its high water content and biomimetic properties simulating extracellular matrix (ECM), hydrogels have been used as preferred cell culture and delivery systems. Similarly, cell-loaded hydrogels can be easily injected into target areas in a minimally invasive manner, minimizing surgical trauma, adapting to irregular shaped defects, and benefiting patients. In this study, we systematically reviewed multiple studies on hydrogel-based bone defect research and briefly summarized the progress of injectable and cell-loaded hydrogels in bone defect repair. METHODS: A systematic search was conducted in the PubMed and Web of Science databases using selected search terms. RESULTS: Initially, 185 articles were retrieved from the databases. After full-text screening based on inclusion and exclusion criteria, 26 articles were included in this systematic review. Data collected from each study included culture model, seed cell type and origin, cell concentration, scaffold material, scaffold shape, experimental animal and site, bioactive agents, and binding method. This injectable and cell-loaded hydrogel shows certain feasibility in bone tissue engineering applications. CONCLUSION: Injectable and cell-loaded hydrogels have been widely applied in bone tissue engineering research. The future direction of bone tissue engineering for bone defect treatment involves the use of new hydrogel materials and biochemical stimulation.

The effect of pore size on the mechanical properties, biodegradation and osteogenic effects of additively manufactured magnesium scaffolds after high temperature oxidation: An in vitro and in vivo study.

The effects of pore size in additively manufactured biodegradable porous magnesium on the mechanical properties and biodegradation of the scaffolds as well as new bone formation have rarely been reported. In this work, we found that high temperature oxidation improves the corrosion resistance of magnesium scaffold. And the effects of pore size on the mechanical characteristics and biodegradation of scaffolds, as well as new bone formation, were investigated using magnesium scaffolds with three different pore sizes, namely, 500, 800, and 1400 µm (P500, P800, and P1400). We discovered that the mechanical characteristics of the P500 group were much better than those of the other two groups. In vitro and in vivo investigations showed that WE43 magnesium alloy scaffolds supported the survival of mesenchymal stem cells and did not cause any local toxicity. Due to their larger specific surface area, the scaffolds in the P500 group released more magnesium ions within reasonable range and improved the osteogenic differentiation of bone mesenchymal stem cells compared with the other two scaffolds. In a rabbit femoral condyle defect model, the P500 group demonstrated unique performance in promoting new bone formation, indicating its great potential for use in bone defect regeneration therapy.

The biological properties of 3D-printed degradable magnesium alloy WE43 porous scaffolds via the oxidative heat strategy.

As a biodegradable material, magnesium alloy has a modulus similar to that of bone, and given the biological activity of its degradation products, it has the potential to be a bone grafting material. Oxidation heat treatment is a very effective passivation method that may reduce the rate of magnesium alloy degradation. Oxidation heat treatment increases the rare earth oxide content of the scaffold as well as the corrosion resistance of the scaffold. The overall cytotoxicity of the as-printed scaffolds (APSs) and oxidation heat-treated scaffolds (OHSs) showed that OHSs accelerated cell proliferation. In the apoptosis experiment, the OHS group had a cell survival rate between that of the control group and of the as-printed group. In the osteogenic induction experiment, the alkaline phosphatase activity and the quantity of mineralized nodules were greater in the APS and OHS groups than in the control group. Marker proteins for bone growth were expressed at higher levels in the APS and OHS groups than in the control group. Therefore, oxidation heat-treated 3D printing scaffolds with good biocompatibility and osteogenic properties have great potential to be made into advanced biomaterials that can be used to fix bone defects.

Biodegradable magnesium alloy WE43 porous scaffolds fabricated by laser powder bed fusion for orthopedic applications: Process optimization, in vitro and in vivo investigation.

Laser powder bed fusion (L-PBF) of magnesium (Mg) alloy porous scaffolds is expected to solve the dual challenges from customized structures and biodegradable functions required for repairing bone defects. However, one of the key technical difficulties lies in the poor L-PBF process performance of Mg, contributed by the high susceptibility to oxidation, vaporization, thermal expansion, and powder attachment etc. This work investigated the influence of L-PBF energy input and scanning strategy on the formation quality of porous scaffolds by using WE43 powder, and characterized the microstructure, mechanical properties, biocompatibility, biodegradation and osteogenic effect of the as-built WE43 porous scaffolds. With the customized energy input and scanning strategy, the relative density of struts reached over 99.5%, and the geometrical error between the designed and the fabricated porosity declined to below 10%. Massive secondary phases including intermetallic precipitates and oxides were observed. The compressive strength (4.37-23.49 MPa) and elastic modulus (154.40-873.02 MPa) were comparable to those of cancellous bone. Good biocompatibility was observed by in vitro cell viability and in vivo implantation. The biodegradation of as-built porous scaffolds promoted the osteogenic effect, but the structural integrity devastated after 12 h by the immersion tests in Hank's solution and after 4 weeks by the implantation in rabbits' femur, indicating an excessively rapid degradation rate.

Expression Patterns and Prognostic Values of ORMDL1 in Different Cancers.

The mammalian orosomucoid-like gene family (ORMDL), containing ORMDL1, ORMDL2, and ORMDL3, is the important regulator of sphingolipid metabolism, which is relevant to cell growth, proliferation, migration, and invasion. Since the role of ORMDL1 in cancers remained unclear, the main purpose of our study was to explore the expression patterns and prognostic values of ORMDL1 in different tumors, especially in cholangiocarcinoma (CHOL), lymphoid neoplasm diffuse large B cell lymphoma (DLBCL), acute myeloid leukemia (LAML), and thymoma (THYM). Bioinformatics tools including GEPIA, CCLE, LinkedOmics, cBioPortal, and TIMER databases were used. As a result, the expression levels of ORMDL1 in tumor tissues and normal tissues varied in different cancers, especially significantly upregulated in CHOL, DLBCL, LAML, and THYM. Moreover, ORMDL1 mRNA was also highly expressed in cell lines of DLBCL and LAML. Further studies showed that ORMDL1 overexpression was associated with poor prognosis in DLBCL, but not significant in CHOL, LAML, and THYM. Consistently, there were genetic alterations of ORMDL1 in DLBCL, and patients with genetic alterations indicated worse survival. Coexpressed genes and related biological events with ORMDL1 in DLBCL were found via LinkedOmics, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The relationship between ORMDL1 and cancer immune cells was investigated, and ORMDL1 expression was positively correlated with infiltrating levels of B cells. In conclusion, ORMDL1 is suggested to be a tumorigenic factor and considered as the potential therapeutic target and prognostic biomarker in DLBCL.