Abstract
Porous nanomaterials (PNMs) are nanosized materials with specially designed porous structures that have been widely used in the bone tissue engineering field due to the fact of their excellent physical and chemical properties such as high porosity, high specific surface area, and ideal biodegradability. Currently, PNMs are mainly used in the following four aspects: (1) as an excellent cargo to deliver bone regenerative growth factors/drugs; (2) as a fluorescent material to trace cell differentiation and bone formation; (3) as a raw material to synthesize or modify tissue engineering scaffolds; (4) as a bio-active substance to regulate cell behavior. Recent advances in the interaction between nanomaterials and cells have revealed that autophagy, a cellular survival mechanism that regulates intracellular activity by degrading/recycling intracellular metabolites, providing energy/nutrients, clearing protein aggregates, destroying organelles, and destroying intracellular pathogens, is associated with the phagocytosis and clearance of nanomaterials as well as material-induced cell differentiation and stress. Autophagy regulates bone remodeling balance via directly participating in the differentiation of osteoclasts and osteoblasts. Moreover, autophagy can regulate bone regeneration by modulating immune cell response, thereby modulating the osteogenic microenvironment. Therefore, autophagy may serve as an effective target for nanomaterials to facilitate the bone regeneration process. Increasingly, studies have shown that PNMs can modulate autophagy to regulate bone regeneration in recent years. This paper summarizes the current advances on the main application of PNMs in bone regeneration, the critical role of autophagy in bone regeneration, and the mechanism of PNMs regulating bone regeneration by targeting autophagy.
Highlights
Autophagy plays a vital role in the differentiation of osteoclasts and osteoblasts via the mediating immune regulation [13]. These results suggest that autophagy plays a bi-directionally regulatory role in the process of promoting or inhibiting osteogenesis; targeting autophagy is of great significance for the design of bone regenerative nanomaterials
Inhibition of autophagy can result in impaired mineralization in vitro and reduced bone mass and volume in vivo, which is followed by oxidative stress and the production of RANKL in general [91]
These results suggest the fundamental role of autophagy in osteoblast differentiation and mineralization, which acts as a mineralization carrier to protect osteoblasts from increased oxidative stress and, in addition, to reduce the production of RANKL, thereby inhibiting osteoclastogenesis during bone formation [91]
Summary
Autophagy plays a vital role in the differentiation of osteoclasts and osteoblasts via the mediating immune regulation [13] These results suggest that autophagy plays a bi-directionally regulatory role in the process of promoting or inhibiting osteogenesis; targeting autophagy is of great significance for the design of bone regenerative nanomaterials. The regulatory roles of PNMs, including mesoporous silica nanoparticles (MSNs) [20,26,27], mesoporous hydroxyapatite nanoparticles (HAP) [28,29,30], alumina nanoparticles (Al2 O3 ) [31,32], mesoporous bioactive glass nanoparticles (MBGNs) [33,34,35,36], mesoporous ceria (MCeO2 ) [37,38], and metallic oxides [39,40] in bone regeneration via targeting autophagy, are reviewed and discussed
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