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REVIEW

Inorganic Nanoparticles-Based Systems in Biomedical Applications of Stem Cells: Opportunities and Challenges

, &
Pages 143-182 | Received 09 Aug 2022, Accepted 09 Dec 2022, Published online: 07 Jan 2023

Figures & data

Figure 1 The differentiation direction of stem cells.

Notes: Reprinted with permission from Baksh D, Song L, Tuan RS. Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy. J Cell Mol Med. 2010;8(3):301–316. Copyright (2010) Wiley-Blackwell.Citation3
Figure 1 The differentiation direction of stem cells.

Figure 2 All kinds of different biomedical application of UCNPs.

Notes: Reprinted with permission from Chen G, Qiu H, Prasad PN, Chen X. Upconversion nanoparticles: design, nanochemistry, and applications in theranostics. Chem Rev. 2014;114(10):5161–5214. Copyright (2014) American Chemical Society, Open Access.Citation15
Figure 2 All kinds of different biomedical application of UCNPs.

Figure 3 NIR light trigger of photo-uncaging and intracellular release of KGN or calcium by UCNPs nanocarriers to control the differentiation of stem cells in vitro and in vivo.

Notes: Reprinted with permission from Kang H, Zhang K, Pan Q, et al. Remote Control of Intracellular Calcium Using Upconversion Nanotransducers Regulates Stem Cell Differentiation In Vivo. Adv Funct Mater. 2018;28(41):681–696. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Citation17
Figure 3 NIR light trigger of photo-uncaging and intracellular release of KGN or calcium by UCNPs nanocarriers to control the differentiation of stem cells in vitro and in vivo.

Figure 4 Schematic illustration of synthesis of UCNPs nanocarriers for tissue penetration of NIR-triggered release of KGN to induce the chondrogenic differentiation of stem cells in vitro and in vivo. (A) The synthesis of UCNP nanocarriers and NIR trigger release KGN of UCNP nanocarriers. (B) Near-infrared light penetrates the skin compared to ultraviolet light for trigger release KGN from UCNP nanocarriers.

Notes: Reprinted from Biomaterials, Volume: 110(9), Li JM, Lee WYW, Wu TY, et al. Near-infrared light-triggered release of small molecules for controlled differentiation and long-term tracking of stem cells in vivo using upconversion nanoparticles. Copyright (2016), with permission from Elsevier.Citation18
Figure 4 Schematic illustration of synthesis of UCNPs nanocarriers for tissue penetration of NIR-triggered release of KGN to induce the chondrogenic differentiation of stem cells in vitro and in vivo. (A) The synthesis of UCNP nanocarriers and NIR trigger release KGN of UCNP nanocarriers. (B) Near-infrared light penetrates the skin compared to ultraviolet light for trigger release KGN from UCNP nanocarriers.

Figure 5 Schematic diagram of “sandwich” structure biosensor that based on UCNPs and the application of detecting dopamine in neural differentiation of stem cells (A), and the comparing energy migration mechanism of Yb/Er codoped UCNPs, Yb/Er@Yb “active-shell” UCNPs and novel Yb@Er@Yb “sandwich” UCNPs (B).

Notes: Reprinted with permission from Rabie H, Zhang Y, Pasquale N, Lagos MJ, Batson PE, Lee KB. NIR Biosensing of Neurotransmitters in Stem Cell-Derived Neural Interface Using Advanced Core–Shell Upconversion Nanoparticles. Adv Mater. 2019;31(14):1806991–1806970. © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Citation23
Figure 5 Schematic diagram of “sandwich” structure biosensor that based on UCNPs and the application of detecting dopamine in neural differentiation of stem cells (A), and the comparing energy migration mechanism of Yb/Er codoped UCNPs, Yb/Er@Yb “active-shell” UCNPs and novel Yb@Er@Yb “sandwich” UCNPs (B).

Figure 6 Schematic diagram of UCNPs substrate for controlling the multidirectional differentiation of stem cells by adjusting the power of NIR light.

Notes: Reprinted with permission from Yan Z, Qin H, Ren J, Qu X. Photocontrolled Multidirectional Differentiation of Mesenchymal Stem Cells on an Upconversion Substrate. Angew Chem Int Ed. 2018;57(35):11182–11187. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.Citation24
Figure 6 Schematic diagram of UCNPs substrate for controlling the multidirectional differentiation of stem cells by adjusting the power of NIR light.

Figure 7 Schematic diagram of UCNPs substrate to control cell adhesion, spreading and multidirectional differentiation of stem cells by adjusting power of NIR light. (A) Synthetic procedure for UCNP@SiO2-RGD-ONA and NIR light-triggered cleavage of an ONA protective group. (B) The potential mechanism underlying the UCNP-substrate RGD photoactivated to control the adhesion, spreading, and differentiation of MSCs, governed by mechanosensing signaling. (C) NIR-triggered release of ONA to control cell adhesion, spreading, and multidifferentiation of MSCs in vivo on the UCNP-substrate by different powers of NIR irradiation.

Notes: Reprinted with permission from Guo YJ, Yan R, Wang XC, Liang GH, Yang AL, Li JM. Near-Infrared Light-Controlled Activation of Adhesive Peptides Regulates Cell Adhesion and Multidifferentiation in Mesenchymal Stem Cells on an Up-Conversion Substrate. Nano Lett. 2022;22(6):2293–2302. Copyright (2022) American Chemical Society.Citation25
Figure 7 Schematic diagram of UCNPs substrate to control cell adhesion, spreading and multidirectional differentiation of stem cells by adjusting power of NIR light. (A) Synthetic procedure for UCNP@SiO2-RGD-ONA and NIR light-triggered cleavage of an ONA protective group. (B) The potential mechanism underlying the UCNP-substrate RGD photoactivated to control the adhesion, spreading, and differentiation of MSCs, governed by mechanosensing signaling. (C) NIR-triggered release of ONA to control cell adhesion, spreading, and multidifferentiation of MSCs in vivo on the UCNP-substrate by different powers of NIR irradiation.

Figure 8 The emission of QDs when compared with organic dyes. (A) Absorption and emission spectrum of six different QDs. (B) Absorption and emission spectrum of two organic dyes, Cy3 and Cy5. (C) Comparison of fluorescence photo graphs of six QD in (A) with CdSe core sizes.

Notes: Reprinted with permission from Pisanic TR, Zhang Y, Wang TH. Quantum Dots in Diagnostics and Detection: Principles and Paradigms. Analyst. 2014;139(12):2968–2981. Copyright (2014) Royal Society of Chemistry.Citation29
Figure 8 The emission of QDs when compared with organic dyes. (A) Absorption and emission spectrum of six different QDs. (B) Absorption and emission spectrum of two organic dyes, Cy3 and Cy5. (C) Comparison of fluorescence photo graphs of six QD in (A) with CdSe core sizes.

Figure 9 Schematic of targeted labeling hEstem cells by different modified QDs. (A) Phages that specifically bind to human ESCs were enriched in the phage pool by two rounds of bio-panning. (B) Illustration of chemical conjugation between the phage and QDs. (C) This enlarged view of (B) shows how the –NH2 groups on the phage are conjugated to the free –COOH groups on the surface of the QDs via EDC.

Notes: Reprinted with permission from Zhao W, Jin L, Yuan H, et al. Targeting human embryonic stem cells with quantum dot-conjugated phages. Sci Rep. 2013;3:3134. Copyright (2013) Springer Nature. Open Access.Citation34
Figure 9 Schematic of targeted labeling hEstem cells by different modified QDs. (A) Phages that specifically bind to human ESCs were enriched in the phage pool by two rounds of bio-panning. (B) Illustration of chemical conjugation between the phage and QDs. (C) This enlarged view of (B) shows how the –NH2 groups on the phage are conjugated to the free –COOH groups on the surface of the QDs via EDC.

Figure 10 Schematic of RGD-CD-QDs as nanocarriers and nanoprobes to deliver small molecule and siRNA for controlling the chondrogenic differentiation of hMSCs and simultaneously long-term tracking hMSCs in vitro and in vivo.

Notes: Reprinted with permission from Xu J, Li J, Lin S, et al. Nanocarrier-Mediated Codelivery of Small Molecular Drugs and siRNA to Enhance Chondrogenic Differentiation and Suppress Hypertrophy of Human Mesenchymal Stem Cells. Adv Funct Mater. 2016;26(15):2463–2472. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Citation38
Figure 10 Schematic of RGD-CD-QDs as nanocarriers and nanoprobes to deliver small molecule and siRNA for controlling the chondrogenic differentiation of hMSCs and simultaneously long-term tracking hMSCs in vitro and in vivo.

Figure 11 Schematic diagram of synthesizing novel MNPs for stem cells labeling and MRI imaging in vivo.

Notes: Reprinted with permission from Lin BL, Zhang JZ, Lu LJ, et al. Superparamagnetic Iron Oxide Nanoparticles-Complexed Cationic Amylose for In Vivo Magnetic Resonance Imaging Tracking of Transplanted Stem Cells in Stroke. Nanomaterials. 2017;7(5):107–124. Creative Commons CC BY.Citation46
Figure 11 Schematic diagram of synthesizing novel MNPs for stem cells labeling and MRI imaging in vivo.

Figure 12 Schematic diagram of the silica coated MNPs modified glass substrate controlled cell adhesion, spreading and differentiation of hMSCs by magnetic field.

Notes: Reprinted with permission from Wong D, Li J, Yan X, et al. Magnetically Tuning Tether Mobility of Integrin Ligand Regulates Adhesion, Spreading, and Differentiation of Stem Cells. Nano Lett. 2017;17(3):1685–1695. Copyright (2017) American Chemical Society.Citation53
Figure 12 Schematic diagram of the silica coated MNPs modified glass substrate controlled cell adhesion, spreading and differentiation of hMSCs by magnetic field.

Figure 13 The RGD peptide conjugated MNPs modified a soft hydrogel substrate to inhibit/enhance the cell adhesion and mechanosensing-dependent differentiation of hMSCs by magnetic field.

Notes: Reprinted with permission from Wong S, Wong W, Lai C, Oh J, Bian L. Soft Polymeric Matrix as a Macroscopic Cage for Magnetically Modulating Reversible Nanoscale Ligand Presentation. Nano Lett. 2020;20(5):3207–3216. Copyright (2020) American Chemical Society.Citation54
Figure 13 The RGD peptide conjugated MNPs modified a soft hydrogel substrate to inhibit/enhance the cell adhesion and mechanosensing-dependent differentiation of hMSCs by magnetic field.

Figure 14 Remote control of multimodal ligand oscillations was used to regulate the adhesion and differentiation of stem cells by altering the oscillation frequency of the magnetic field.

Notes: Reprinted with permission from Kang H, Wong D, Yan X, et al. Remote Control of Multimodal Nanoscale Ligand Oscillations Regulates Stem Cell Adhesion and Differentiation. ACS Nano. 2017;11(10):9636–9649. Copyright (2017) American Chemical Society.Citation55
Figure 14 Remote control of multimodal ligand oscillations was used to regulate the adhesion and differentiation of stem cells by altering the oscillation frequency of the magnetic field.

Figure 15 Schematic diagram of MNPs/AuNPs hybrid system nano-substrate was remotely controlled to regulate cell adhesion, spreading and differentiation of stem cells by reversibly manipulating RGD ligand cage and uncaging utilizing magnetic field.

Notes: Reprinted with permission from Kang H, Jung HJ, Wong DSH. Remote Control of Heterodimeric Magnetic Nanoswitch Regulates the Adhesion and Differentiation of Stem Cells. J Am Chem Soc. 2018;140(18):5909–5913. Copyright (2018) American Chemical Society.Citation56
Figure 15 Schematic diagram of MNPs/AuNPs hybrid system nano-substrate was remotely controlled to regulate cell adhesion, spreading and differentiation of stem cells by reversibly manipulating RGD ligand cage and uncaging utilizing magnetic field.

Figure 16 Schematic diagram of intracellular internalization and endolysosomal escape of FITC-MSNs in hMSCs.

Notes: Reprinted with permission from Huang DM, Hung Y, Ko BS, et al. Highly efficient cellular labeling of mesoporous nanoparticles in human mesenchymal stem cells: implication for stem cell tracking. FASEB J. 2005;19(14): 2014–2016. Copyright (2005) © FASEB.Citation58
Figure 16 Schematic diagram of intracellular internalization and endolysosomal escape of FITC-MSNs in hMSCs.

Figure 17 Schematic diagram of theranostic MSNs and characteristic of MSNs. (A) MSNs have impedance mismatch to backscatter ultrasound, MRI signal via Gd3+ and optical signal from fluo rescein. (B) TEM image of MSNs. (C) Enlarged TEM image of MSNs with 4.1 nm pores. (D) Red box in B indicates area imaged at higher magnification in C, line in C is representative of profile used to construct D. (E) DLS of MSNs. (F) EDS of MSNs shows expected peaks for silicon and oxygen as well as gadolinium from the secondary tag. (G) Histogram of MSN sizes from the TEM data in nm.

Notes: Reprinted with permission from Kempen PJ, Sarah G, Parker KA, et al. Theranostic Mesoporous Silica Nanoparticles Biodegrade after Pro-Survival Drug Delivery and Ultrasound/Magnetic Resonance Imaging of Stem Cells. Theranostics. 2015;5(6):631–642. Copyright (2005) Ivyspring International Publisher, Open Access.Citation60
Figure 17 Schematic diagram of theranostic MSNs and characteristic of MSNs. (A) MSNs have impedance mismatch to backscatter ultrasound, MRI signal via Gd3+ and optical signal from fluo rescein. (B) TEM image of MSNs. (C) Enlarged TEM image of MSNs with 4.1 nm pores. (D) Red box in B indicates area imaged at higher magnification in C, line in C is representative of profile used to construct D. (E) DLS of MSNs. (F) EDS of MSNs shows expected peaks for silicon and oxygen as well as gadolinium from the secondary tag. (G) Histogram of MSN sizes from the TEM data in nm.

Figure 18 Schematic illustration and characterization of the stem cell-based multifunctional MSN-based platform for targeting delivery. (A) Schematic of the structure of the MSC-platform showing the internal and external layer. (B) The fluorescence properties of the MSNs. (C) TEM images of MSNs before and after HA coating. (D) and (E) 3D co-localization imaging of MSC-platform by confocal microscopy. The signal intensity (white line) of actin, particles and nucleus were quantified (E).

Notes: Reprinted from Biomaterials. Volume: 34(7), Huang X, Fan Z, Wang H, et al. Mesenchymal stem cell-based cell engineering with multifunctional mesoporous silica nanoparticles for tumor delivery. Biomaterials. 2013;34(7):1772–1780. Copyright (2013), with permission from Elsevier.Citation61
Figure 18 Schematic illustration and characterization of the stem cell-based multifunctional MSN-based platform for targeting delivery. (A) Schematic of the structure of the MSC-platform showing the internal and external layer. (B) The fluorescence properties of the MSNs. (C) TEM images of MSNs before and after HA coating. (D) and (E) 3D co-localization imaging of MSC-platform by confocal microscopy. The signal intensity (white line) of actin, particles and nucleus were quantified (E).

Figure 19 Schematic illustration of synthesis of the DEX@MSNs-pep nanocomplexes and the size distribution of MSNs and MSNs-pep by TEM and DLS. (A) Schematic illustration for the preparation of DEX@MSNs-pep. (B) TEM images of MSNs (inset is the enlarged image). (C) MSNs-pep. (D) Size distribution of MSNs and MSNs-pep.

Notes: Reprinted with permission from Zhou X, Feng W, Qiu K, et al. BMP-2 derived peptide and dexamethasone incorporated mesoporous silica nanoparticles for enhanced osteogenic differentiation of bone mesenchymal stem cells. ACS Appl Mater Interfaces. 2015;7(29):15777–15789. Copyright (2015) American Chemical Society.Citation62
Figure 19 Schematic illustration of synthesis of the DEX@MSNs-pep nanocomplexes and the size distribution of MSNs and MSNs-pep by TEM and DLS. (A) Schematic illustration for the preparation of DEX@MSNs-pep. (B) TEM images of MSNs (inset is the enlarged image). (C) MSNs-pep. (D) Size distribution of MSNs and MSNs-pep.

Figure 20 Schematic illustration of PLGA/MSH-AL’s three-level structure.

Notes: Reprinted from Biomaterials, Volume: 30(23-24), Shi X, Wang Y, Varshney RR, Li R, Feng Z, Wang DA. In-vitro osteogenesis of synovium stem cells induced by controlled release of bisphosphate additives from microspherical mesoporous silica composite. 3996–4005. Copyright (2009), with permission from Elsevier.Citation63
Figure 20 Schematic illustration of PLGA/MSH-AL’s three-level structure.

Figure 21 Schematic diagram of fabrication and application of GO-based nanofiber hybrid scaffolds for enhancing the differentiation of mature oligodendrocytes in stem cells.

Notes: Reprinted with permission from Shah S, Yin PT, Uehara TM, Chueng S, Yang L, Lee KB. Guiding Stem Cell Differentiation into Oligodendrocytes Using GO-Nanofiber Hybrid Scaffolds. Adv Mater. 2014;26(22):3673–3680. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Citation69
Figure 21 Schematic diagram of fabrication and application of GO-based nanofiber hybrid scaffolds for enhancing the differentiation of mature oligodendrocytes in stem cells.

Figure 22 Schematic illustration of multifunctional GO-Au hybrid nanoelectrode arrays (NEAs) and its application for enhancing the differentiation of stem cells and monitoring the osteogenic differentiation of stem cell. (A) Investigation of the combinatorial effects of physicochemical cues on stem cell. (B) Identification of optimal biophysical cues for stem cell differentiation. (C) Enhanced electrochemical signal for monitoring osteogenic differentiation.

Notes: Reprinted with permission from Lee JH, Choi HK, Yang L, Chueng SD, Choi JW, Lee KB. Nondestructive Real-Time Monitoring of Enhanced Stem Cell Differentiation Using a GO-Au Hybrid Nanoelectrode Array. Adv Mater. 2018;30(39):1802762–1802770. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Citation70
Figure 22 Schematic illustration of multifunctional GO-Au hybrid nanoelectrode arrays (NEAs) and its application for enhancing the differentiation of stem cells and monitoring the osteogenic differentiation of stem cell. (A) Investigation of the combinatorial effects of physicochemical cues on stem cell. (B) Identification of optimal biophysical cues for stem cell differentiation. (C) Enhanced electrochemical signal for monitoring osteogenic differentiation.

Figure 23 Schematic illustration of the GO modified substrate and its application of promoting the cell adhesion of hNSCs and enhancing the differentiation into neurons by GO.

Notes: Reprinted with permission from Park SY, Park J, Sim SH, et al. Enhanced Differentiation of Human Neural Stem Cells into Neurons on GO. Adv Mater. 2011;23(36):263–267. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Citation71
Figure 23 Schematic illustration of the GO modified substrate and its application of promoting the cell adhesion of hNSCs and enhancing the differentiation into neurons by GO.

Figure 24 Schematic illustration of the SiO2 modified, GO modified and SiO2-GO modified substrates and their application of inducing the neuronal differentiation and axonal alignment of hNSCs. (A) Different control and experimental conditions for differentiating hNSCs into neurons. (B) hNSCs cultured and differentiated on Substrate D having a monolayer of NPs coated with GO show enhanced neuronal differentiation and axonal alignment.

Notes: Reprinted with permission from Solanki A, Chueng S T D, Yin P T, et al. Axonal alignment and enhanced neuronal differentiation of neural stem cells on graphene-nanoparticle hybrid structures. Adv Mater. 2013;25(38):5477–5482. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Citation72
Figure 24 Schematic illustration of the SiO2 modified, GO modified and SiO2-GO modified substrates and their application of inducing the neuronal differentiation and axonal alignment of hNSCs. (A) Different control and experimental conditions for differentiating hNSCs into neurons. (B) hNSCs cultured and differentiated on Substrate D having a monolayer of NPs coated with GO show enhanced neuronal differentiation and axonal alignment.

Figure 25 The annealed-GO modified substrate exhibited a higher amount of molecular adsorption and peptide-grafted content, enabling the osteogenic differentiation of hMSCs toward oxygen content.

Notes: Reprinted with permission from Yang JW, Hsieh KY, Kumar PV, et al. Enhanced Osteogenic Differentiation of Stem Cells on PhaseEngineered GO. ACS Appl Mater Inter. 2018;10(15):12497–12503. Copyright (2018) American Chemistry Society.Citation75
Figure 25 The annealed-GO modified substrate exhibited a higher amount of molecular adsorption and peptide-grafted content, enabling the osteogenic differentiation of hMSCs toward oxygen content.

Figure 26 The application of AuNPs in biomedical field.

Notes: Reprinted with permission from Yeh YC, Creran B, Rotello VM. Gold nanoparticles: preparation, properties, and applications in bionanotechnology. Nanoscale. 2012;4(6):1871–1870. Copyright (2012) Royal Society of Chemistry.Citation77
Figure 26 The application of AuNPs in biomedical field.

Figure 27 The different size and shape of AuNPs affect the osteogenic differentiation response of hMSCs.

Notes: Reprinted with permission from Li J, Li J, Zhang J, Wang X, Kawazoe N, Chen G. Gold nanoparticle size and shape influence on osteogenesis of mesenchymal stem cells. Nanoscale. 2016;8(15):7992–8007. Copyright (2016) Royal Society of Chemistry.Citation84
Figure 27 The different size and shape of AuNPs affect the osteogenic differentiation response of hMSCs.

Figure 28 Schematic illustration of a two-nanoparticle system for labeling mesenchymal stem cells with gold nanorods and macrophages with gold nanospheres.

Notes: Reprinted with permission from Ricles LM, Nam SY, Treviño EA, Emelianov SY, Suggs LJ. A dual gold nanoparticle system for mesenchymal stem cell tracking. J Mater Chem B. 2014;2(46):8220–8230. Copyright (2014) Royal Society of Chemistry.Citation86
Figure 28 Schematic illustration of a two-nanoparticle system for labeling mesenchymal stem cells with gold nanorods and macrophages with gold nanospheres.

Figure 29 AuNPs (AuNP-PEI-peptide-FITC) and siRNA can silence PPARg gene to control osteogenic differentiation, and detect the cell differentiation level in hMSCs in real time.

Notes: Reprinted with permission from Wu Q, Wang K, Wang X, Liang G, Li J. Delivering siRNA to control osteogenic differentiation and real-time detection of cell differentiation in human mesenchymal stem cells using multifunctional gold nanoparticles. J Mater Chem B. 2020;8(15):3016–3027. Copyright (2020) Royal Society of Chemistry.Citation89
Figure 29 AuNPs (AuNP-PEI-peptide-FITC) and siRNA can silence PPARg gene to control osteogenic differentiation, and detect the cell differentiation level in hMSCs in real time.

Figure 30 The AuNPs modified RGD-coupled substrate and its application of controlling cell adhesion, spreading and differentiation of stem cell by different coupling strength.

Notes: Reprinted with permission from Choi C, Xu YJ, Wang B, Zhu M, Zhang L, Bian L. Substrate Coupling Strength of Integrin-Binding Ligands Modulates Adhesion, Spreading, and Differentiation of Human Mesenchymal Stem Cells. Nano Lett. 2015;15(10):6592–6600. Copyright (2015) American Chemical Society.Citation92
Figure 30 The AuNPs modified RGD-coupled substrate and its application of controlling cell adhesion, spreading and differentiation of stem cell by different coupling strength.

Figure 31 Schematic of four modified AuNPs modified matrices to study the effect of matrix stiffness and organization of cell adhesion ligands on adhesion and differentiation of rat mesenchymal stem cells.

Notes: Reprinted with permission from Ye K, Wang X, Cao L, et al. Matrix Stiffness and Nanoscale Spatial Organization of Cell-Adhesive Ligands Direct Stem Cell Fate. Nano Lett. 2015;15(7):4720–4729. Copyright (2015) American Chemical Society.Citation93
Figure 31 Schematic of four modified AuNPs modified matrices to study the effect of matrix stiffness and organization of cell adhesion ligands on adhesion and differentiation of rat mesenchymal stem cells.

Figure 32 Schematic representation of the RGD-AuNPs modified micro/nanopatterns with different RGD nanospacings to control the cell spreading size and cell differentiation of stem cells.

Notes: Reprinted with permission from Wang X, Li S, Yan C, Liu P, Ding J. Fabrication of RGD Micro/Nanopattern and Corresponding Study of Stem Cell Differentiation. Nano Lett. 2015;15(3):1457–1467. Copyright (2015) American Chemical Society.Citation94
Figure 32 Schematic representation of the RGD-AuNPs modified micro/nanopatterns with different RGD nanospacings to control the cell spreading size and cell differentiation of stem cells.

Figure 33 Schematic summary and characterization of the array of RGD-bearing gold nanorods (AuNRs) modified glass with various aspect ratios (ARs, 1, 2, 4, and 7) for enhanced cell adhesion and osteogenic differentiation in stem cells. (AC) Schematic illustration of fabrication of immobilized RGD-conjugated AuNRs substrate blocked by nonfouling poly(ethylene) glycol. (D) UV–vis absorbance of AuNRs with different aspect ratios. (EH) TEM images of AuNRs with different aspect ratios. (IL) SEM images of AuNRs with different aspect ratios. (MP) Schematic illustration postulation of how AuNRs with various ARs regulate cell adhesion structures, the differential recruitment and spatial organization of different integer.

Notes: Reprinted with permission from Wong SHD, Yin B, Yang B, et al. Anisotropic Nanoscale Presentation of Cell Adhesion Ligand Enhances the Recruitment of Diverse Integrins in Adhesion Structures and Mechanosensing Dependent Differentiation of Stem Cells. Adv Funct Mater. 2019;29(8):1806812–1806822. © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Citation95
Figure 33 Schematic summary and characterization of the array of RGD-bearing gold nanorods (AuNRs) modified glass with various aspect ratios (ARs, 1, 2, 4, and 7) for enhanced cell adhesion and osteogenic differentiation in stem cells. (A–C) Schematic illustration of fabrication of immobilized RGD-conjugated AuNRs substrate blocked by nonfouling poly(ethylene) glycol. (D) UV–vis absorbance of AuNRs with different aspect ratios. (E–H) TEM images of AuNRs with different aspect ratios. (I–L) SEM images of AuNRs with different aspect ratios. (M–P) Schematic illustration postulation of how AuNRs with various ARs regulate cell adhesion structures, the differential recruitment and spatial organization of different integer.

Figure 34 Schematic representation of the preparation of Au@PDA NPs nanoprobe and its application of real-time detecting the osteogenic differentiation in living hMSCs by intracellular detection of miRNAs. (A) Preparation of the Polydopamine-Coated Gold Nanoparticles (Au@PDA NPs) and Hairpin-DNA-Based (hpDNA) Nanoprobes. (B) Intracellular Detection of miRNAs in Living Human Mesenchymal Stem Cells.

Notes: Reprinted with permission from Choi C, Li J, Wei K, et al. A Gold@Polydopamine Core–Shell Nanoprobe for Long-Term Intracellular Detection of MicroRNAs in Differentiating Stem Cells. J Am Chem Soc. 2015;137(23):7337–7346. Copyright (2015) American Chemical Society.Citation96
Figure 34 Schematic representation of the preparation of Au@PDA NPs nanoprobe and its application of real-time detecting the osteogenic differentiation in living hMSCs by intracellular detection of miRNAs. (A) Preparation of the Polydopamine-Coated Gold Nanoparticles (Au@PDA NPs) and Hairpin-DNA-Based (hpDNA) Nanoprobes. (B) Intracellular Detection of miRNAs in Living Human Mesenchymal Stem Cells.

Figure 35 Detection strategy to monitor differentiation of mNSCs by the GO-encapsulated AuNPs substrate through the change of SERS signals.

Notes: Reprinted from Biomaterials, Volume: 34(34), Kim TH, Lee KB, Choi JW. 3D GO-encapsulated gold nanoparticles to detect neural stem cell differentiation. 8660–8670. Copyright (2013), with permission from Elsevier.Citation98
Figure 35 Detection strategy to monitor differentiation of mNSCs by the GO-encapsulated AuNPs substrate through the change of SERS signals.

Figure 36 By controlling the arrangement of carbon nanotubes, hMSCs can grow and differentiate in the carbon nanotube network. (A) Schematic diagram showing the experimental procedure. (B) Plausible model to explain the hMSC responses to the aligned and the randomly oriented CNT networks.

Notes: Reprinted with permission from Namgung S, Baik KY, Park J, Hong S. Controlling the growth and differentiation of human mesenchymal stem cells by the arrangement of individual carbon nanotubes. ACS Nano. 2011;5(9):7383–7390. Copyright (2011) American Chemical Society.Citation105
Figure 36 By controlling the arrangement of carbon nanotubes, hMSCs can grow and differentiate in the carbon nanotube network. (A) Schematic diagram showing the experimental procedure. (B) Plausible model to explain the hMSC responses to the aligned and the randomly oriented CNT networks.

Figure 37 Schematic representation of using carboxylated MWCNTs to regulated the neural gene expression in hBMMSCs in the basal medium.

Notes: Reprinted from Biomaterials, Volume: 34(21), Chen YS, Hsiue GH. Directing neural differentiation of mesenchymal stem cells by carboxylated multiwalled carbon nanotubes. 4936–4944. Copyright (2013), with permission from Elsevier.Citation111
Figure 37 Schematic representation of using carboxylated MWCNTs to regulated the neural gene expression in hBMMSCs in the basal medium.

Figure 38 A summary of the biomedical applications map of inorganic nanoparticles, including the current research progresses in laboratories and challenges.

Figure 38 A summary of the biomedical applications map of inorganic nanoparticles, including the current research progresses in laboratories and challenges.