Recent advances of bone tissue engineering: carbohydrate and ceramic materials, fundamental properties and advanced biofabrication strategies ‒ a comprehensive review.

Bone is a dynamic tissue that can always regenerate itself through remodeling to maintain biofunctionality. This tissue performs several vital physiological functions. However, bone scaffolds are required for critical-size damages and fractures, and these can be addressed by bone tissue engineering. Bone tissue engineering (BTE) has the potential to develop scaffolds for repairing critical-size damaged bone. BTE is a multidisciplinary engineered scaffold with the desired properties for repairing damaged bone tissue. Herein, we have provided an overview of the common carbohydrate polymers, fundamental structural, physicochemical, and biological properties, and fabrication techniques for bone tissue engineering. We also discussed advanced biofabrication strategies and provided the limitations and prospects by highlighting significant issues in bone tissue engineering. There are several review articles available on bone tissue engineering. However, we have provided a state-of-the-art review article that discussed recent progress and trends within the last 3-5 years by emphasizing challenges and future perspectives.

Substrate stiffness affects the immunosuppressive and trophic function of hMSCs via modulating cytoskeletal polymerization and tension.

Mesenchymal stem cells (MSCs) have broad therapeutic potential due to their ability to secrete bioactive factors that are immunomodulatory and trophic (regenerative). In this study, polyacrylamide (PAAm) hydrogels with different stiffness are used as a model to explore the effects of substrate stiffness on the paracrine function of human mesenchymal stem cells (hMSCs). Human MSCs cultured on soft substrates produced significantly higher levels of immunomodulatory and trophic factors compared with hMSCs cultured on rigid substrates. The enhanced paracrine function of hMSCs is further confirmed by the M2 phenotypic polarization observed in macrophages, as well as the accelerated chemotactic migration and angiogenesis capacity observed in human umbilical vein endothelial cells (HUVECs) after treatment with conditioned media (CM) collected from hMSCs cultured on soft substrates. Furthermore, the inhibited secretion of immunosuppressive and trophic factors by hMSCs cultured on rigid substrates is largely rescued by treatment with Lat.A, a cytoskeletal polymerization inhibitor. Similar results are observed after treatment with either myosin (Blebbi) or ROCK (Y27632) inhibitors. These results demonstrate that substrate stiffness is a key modulator of the paracrine function of hMSCs and highlight the potential utility of promoting tissue repair through stiffness-regulated paracrine signaling in MSCs.

Synergistic effect of strontium and silicon in strontium-substituted sub-micron bioactive glass for enhanced osteogenesis.

Strontium-substituted sub-micron bioactive glasses (Sr-SBG) have been reported to have enhanced osteogenic differentiation capacity compared to sub-micron bioactive glasses (SBG) in our previous study. However, the underlying molecular mechanisms of such beneficial effect of Sr-SBG are still not fully understood. In this study, we synthesized Sr-SBG, studied the effects of Sr-SBG on proliferation and osteogenic differentiation of mouse mesenchymal stem cells (mMSCs), and identified the molecular mechanisms of the enhancement effect of Sr-SBG on mMSCs. The results demonstrated that Sr-SBG had more profound promotion effect on proliferation and osteogenic differentiation of mMSCs than SBG and SrCl2 group which containing identical Sr concentration with Sr-SBG group. RT-qPCR and western blot analysis showed that the mRNA expressions and protein expressions involved in NFATc and Wnt/ß-catenin signaling pathways were all upregulated mediated by Sr-SBG, while only Wnt/ß-catenin signaling pathway related genes upregulated in SBG group and only NFATc signaling pathway activated in SrCl2 group, suggesting that NFATc and Wnt/ß-catenin signaling pathways played important roles in osteogenesis enhancement induced by Sr-SBG. To conform the above conclusion, cyclosporin A (CSA) was applied to inhibit NFATc signaling pathway. It was found that the enhanced osteogenic differentiation of mMSCs induced by Sr-SBG was partially abrogated and the activated Wnt/ß-catenin signaling pathway was also inhibited in part. However, the effects of SBG on proliferation and osteogenesis of mMSCs were unimpaired, yet the effects of SrCl2 were greatly suppressed. Taken together, these results indicated that strontium activated NFATc signaling pathway and silicate activated Wnt/ß-catenin signaling pathway might synergistically mediated the enhanced osteogenesis induced by Sr-SBG.

Cationic Polyarginine Conjugated Mesoporous Bioactive Glass Nanoparticles with Polyglycerol Coating for Efficient DNA Delivery.

Mesoporous bioactive glass (MBG) is a type of material with high biological activity and excellent biocompatibility. Because of its high specific surface area and adjustable surface morphology, MBG is usable for loading and delivering molecules. In our previous report, MBG particles were used as gene vectors and showed good transfection rate. In this paper, MBG, prepared through a sacrificial liquid template method in sol­gel process, was covered with polyglycerol (PG) and the resulting MBG-PG was further functionalized with octaarginine (Arg8. More specifically, MBG-PG-Arg8 particles were synthesized by PG functionalization of MBG through ring-opening polymerization of glycidol on the MBG surface, followed by multistep organic transformations (­OH→ ­OTs (tosylate)→ ­N3 in the PG layer and click conjugation of the Arg8 terminated with propargyl glycine. MBG-PG-Arg8 was successfully taken up by cells more efficiently due to the cellpenetrating property of Arg8, and thus showed higher plasmid DNA loading and cell transfection efficiency than MBG modified with amino groups. This novel arginine-functionalized MBG may be a good candidate as a vector for gene delivery with higher efficiency.