In addition, the obstacles to the application of inorganic NMs and the corresponding solutions were further analyzed. In this paper, we summarized the progress of various inorganic NMs on the regulation of stem cells differentiation, and the physical properties of inorganic NMs in regulating stem cell differentiation were discussed. The stiffness, size and shape of inorganic NMs can directly affect the bioactivity of materials and, in turn, affect the differentiation of stem cells ( Huang et al., 2020). Various inorganic NMs, including graphene ( Rostami et al., 2020), carbon dots ( Shao et al., 2017), gold nanoparticles (AuNPs) ( Heo et al., 2014), silver nanoparticles (AgNPs) ( Wan et al., 2020), nano titanium-based alloys ( Jalali et al., 2020), strontium nanoparticles ( Hu et al., 2017), iron oxides nanoparticles ( Zhang et al., 2020), manganese dioxide (MnO 2) nanoparticles ( Wang et al., 2017), silicon dioxide (SiO 2) nanoparticles ( Gandhimathi et al., 2019), and black phosphorus (BP) nanosheets ( Xu et al., 2020), have been extensively explored in stem cells regeneration medicine. Inorganic NMs exert their influence on stem cell behavior as unique biomolecules, besides that, as modifiable non-viral transfection vectors, inorganic NMs can carry various bioactive molecules that regulate stem cell behavior, including RNA, plasmids, proteins, or polypeptides, etc., thereby further stimulating the proliferation, migration, differentiation and paracrine behavior of stem cells. In recent years, inorganic NMs have been widely used to manipulate the fate of stem cells. Inorganic NMs have been widely used in bioimaging, drug delivery, biosensing, photothermal therapy, and 3D printing due to their own excellent properties ( Wu et al., 2018 Mashayekhi et al., 2020 Tavares et al., 2021). To be able to fully realize the therapeutic potential of stem cells in the field of regenerative medicine, precise control of the fate of stem cells is one of the first issues to be addressed ( Solanki et al., 2013b). Changing the size, hydrophilicity, roughness, and arrangement of the cell attachment surface can directly affect cell behavior ( Zanden et al., 2014). The growth and differentiation of stem cells are easily affected by their surrounding matrix. With the increasing of research on stem cells in recent years, more and more evidence is emerging that stem cell transplantation is one of the most effective methods to treat neurological diseases, bone injury and other diseases ( Yang et al., 2018 Krukiewicz et al., 2020). Terminally differentiated somatic cells can be reprogrammed into induced pluripotent stem cells (iPSC) with embryonic stem cells (ESCs)-like properties by transfection of defined factors ( Takahashi and Yamanaka, 2006), and further differentiate into different cell types. Typical somatic stem cells include mesenchymal stem cells (MSCs), neural stem cells (NSCs), hematopoietic stem cells (HSCs) and so on. Embryonic stem cells are derived from blastocysts ( Reubinoff et al., 2000). Stem cells refer to cells with self-renewal and differentiation capacity, which can be roughly divided into embryonic stem cells and somatic stem cells. In addition, we further analyzed the existing obstacles and corresponding perspectives of the application of inorganic NMs in the field of stem cells. In this mini review, we summarized the recent advances of common inorganic NMs in regulating stem cells differentiation, and the effects of the stiffness, size and shape of inorganic NMs on stem cell behavior were discussed. In addition, inorganic NMs have huge specific surface area and modifiability that can be used as vectors to transport plasmids, proteins or small molecules to further interfere with the fate of stem cells. Inorganic nanomaterials (NMs), due to their unique physical and chemical properties, can affect the adhesion, migration, proliferation and differentiation of stem cells. In order to optimize the therapeutic effect of stem cell transplantation, it is necessary to intervene in stem cell differentiation. Transplanting stem cells with the abilities of self-renewal and differentiation is one of the most effective ways to treat many diseases. School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, China.Fumei He, Jinxiu Cao, Junyang Qi, Zeqi Liu, Gan Liu* and Wenbin Deng*
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