In Situ and Ex Situ Studies of Ring-Like Assembly of Silica Nanoparticles in the Presence of Poly(propylene oxide)-Poly(ethylene oxide) Block Copolymers.

Block copolymer-mediated self-assembly of colloidal nanoparticles has attracted great attention for fabricating various nanoparticle arrays. We have previously shown that silica nanoparticles (SNPs) assemble into ring-like nanostructures in the presence of temperature-responsive block copolymers poly[(2-ethoxyethyl vinyl ether)-block-(2-methoxyethyl vinyl ether)] (PEOVE-PMOVE) in an aqueous phase. The ring-like nanostructures formed within an aggregate of PEOVE-PMOVE when the temperature was increased to 45 °C, at which the polymer is amphiphilic. Herein, we report that SNPs assemble into ring-like nanostructures even with a different temperature-responsive, amphiphilic block copolymer poly(propylene oxide)-block-poly(ethylene oxide) (PPO-PEO) at 45 °C. Field-emission scanning electron microscopy for SNP assemblies that were spin-coated on a substrate indicated that SNP first assembled into chain-like nanostructures and then bent into closed loops over several days. In contrast, in situ small-angle X-ray diffraction measurements revealed the formation of SNP nanorings within 75 s at 45 °C in the liquid phase. These results indicated that ring-like assembly of SNPs occurs quickly in the liquid phase, but the slow formation of Si-O-Si bonds between SNPs leads to their structure being destroyed by spin-coating. Intriguingly, SNPs with a diameter of 15 nm form a well-defined nanoring structure, with five SNPs located at the vertex points of a regular pentagon. Additionally, small-angle neutron scattering, where the contrast of the solvent (a mixture of H2O and D2O) matches that of SNPs, clarified that SNPs are contained within the spherical micelle formed from PPO-PEO. This work offers a facile and versatile approach to preparing ring-like arrays from inorganic colloidal nanoparticles, leading to applications including sensing, catalysis, and nanoelectronics.

Transformation behaviour of salts composed of calcium ions and phosphate esters with different linear alkyl chain structures in a simulated body fluid modified with alkaline phosphatase.

Ceramic biomaterials have been used for the treatment of bone defects and have stimulated intense research on such materials. We have previously reported that a salt composed of calcium ions and a phosphate ester (SCPE) transformed into hydroxyapatite (HAp) in a simulated body fluid (SBF) modified with alkaline phosphatase (ALP), and proposed SCPEs as a new category of ceramic biomaterials, namely bioresponsive ceramics. However, the factors that affect the transformation of SCPEs to HAp in the SBF remained unclear. Therefore, in this study, we investigated the behaviour of calcium salts of methyl phosphate (CaMeP), ethyl phosphate (CaEtP), butyl phosphate (CaBuP), and dodecyl phosphate (CaDoP) in SBF with and without ALP modification. For the standard SBF, an X-ray diffraction (XRD) analysis indicated that these SCPEs did not readily transform into calcium phosphate. However, CaMeP, CaEtP, and CaBuP were transformed into HAp and octacalcium phosphate in the SBF modified with ALP; therefore, these SCPEs can be categorised as bioresponsive ceramics. Although CaDoP did not exhibit a sufficient response to ALP to be detected by XRD, it is likely to be a bioresponsive ceramic based on the results of morphological observations. The transformation rate for the SCPEs decreased with increasing size of the linear alkyl group of the phosphate esters. The rate-determining steps for the transformation reaction of the SCPEs were changed from the dissolution of the SCPEs to the hydrolysis of the phosphate esters with increasing size of the phosphate ester alkyl groups. These findings contribute to designing novel bioresponsive ceramic biomaterials.

In Vivo Multimodal Imaging of Stem Cells Using Nanohybrid Particles Incorporating Quantum Dots and Magnetic Nanoparticles.

The diagnosis of the dynamics, accumulation, and engraftment of transplanted stem cells in vivo is essential for ensuring the safety and the maximum therapeutic effect of regenerative medicine. However, in vivo imaging technologies for detecting transplanted stem cells are not sufficient at present. We developed nanohybrid particles composed of dendron-baring lipids having two unsaturated bonds (DLU2) molecules, quantum dots (QDs), and magnetic nanoparticles in order to diagnose the dynamics, accumulation, and engraftment of transplanted stem cells, and then addressed the labeling and in vivo fluorescence and magnetic resonance (MR) imaging of stem cells using the nanohybrid particles (DLU2-NPs). Five kinds of DLU2-NPs (DLU2-NPs-1-5) composed of different concentrations of DLU2 molecules, QDs525, QDs605, QDs705, and ATDM were prepared. Adipose tissue-derived stem cells (ASCs) were labeled with DLU2-NPs for 4 h incubation, no cytotoxicity or marked effect on the proliferation ability was observed in ASCs labeled with DLU2-NPs (640- or 320-fold diluted). ASCs labeled with DLU2-NPs (640-fold diluted) were transplanted subcutaneously onto the backs of mice, and the labeled ASCs could be imaged with good contrast using in vivo fluorescence and an MR imaging system. DLU2-NPs may be useful for in vivo multimodal imaging of transplanted stem cells.

Organic modification of layered zirconium phosphate/phosphonate for controlled release of therapeutic inorganic ions.

The present study aims to develop a layered zirconium phosphate/phosphonate (LZP) powder to control the release of therapeutic inorganic ions. Organically modified LZPs were successfully prepared with various contents of phenyl groups via a reflux method in an aqueous solution containing phosphoric and phenylphosphonic acids. Powder X-ray diffraction analysis and Fourier transform infrared spectroscopy revealed that the crystal structure of the synthesized LZP samples was identical to that of α-zirconium phosphate, even after modification. The amount of incorporated organic molecules increased with increasing molar fractions of phenylphosphonic acid in the starting composition, as determined from the thermal analysis. Cobalt ion (Co2+), a type of therapeutic inorganic ion, was incorporated into the organically modified LZP through treatment with an acetonitrile solution containing tetrabutylammonium ions, followed by treatment with an acetonitrile solution containing CoCl2. The amount of incorporated Co2+ depended on the concentration of the phenyl groups. Furthermore, the highest amount of Co2+ was incorporated in the sample (ZP-Ph-0.5) prepared with equimolar phosphoric/phenylphosphonic acid. The ZP-Ph-0.5 sample additionally showed the ability to incorporate copper or iron ions (Cu2+ or Fe3+). The incorporated ion, either Co2+ or Cu2+, was continuously released from the ZP-Ph-0.5 sample in a saline solution over a period of three weeks, whereas the release of Fe3+ was negligible. The quantity of Co2+ released was higher than that of Cu2+. The controlled release of Co2+ from the ZP-Ph-0.5 sample was also observed in a simulated body fluid that mimicked the ionic concentration of human blood plasma. These results confirm that a specific degree of phenyl modification makes LZP a candidate host material for releasing therapeutic inorganic ions.

Thixotropic Hydrogels Composed of Self-Assembled Nanofibers of Double-Hydrophobic Elastin-Like Block Polypeptides.

Physically crosslinked hydrogels with thixotropic properties attract considerable attention in the biomedical research field because their self-healing nature is useful in cell encapsulation, as injectable gels, and as bioinks for three-dimensional (3D) bioprinting. Here, we report the formation of thixotropic hydrogels containing nanofibers of double-hydrophobic elastin-like polypeptides (ELPs). The hydrogels are obtained with the double-hydrophobic ELPs at 0.5 wt%, the concentration of which is an order of magnitude lower than those for previously reported ELP hydrogels. Although the kinetics of hydrogel formation is slower for the double-hydrophobic ELP with a cell-binding sequence, the storage moduli G' of mature hydrogels are similar regardless of the presence of a cell-binding sequence. Reversible gel-sol transitions are demonstrated in step-strain rheological measurements. The degree of recovery of the storage modulus G' after the removal of high shear stress is improved by chemical crosslinking of nanofibers when intermolecular crosslinking is successful. This work would provide deeper insight into the structure-property relationships of the self-assembling polypeptides and a better design strategy for hydrogels with desired viscoelastic properties.

Designer Biopolymers: Self-Assembling Proteins and Nucleic Acids.

Nature has evolved sequence-controlled polymers such as DNA and proteins over its long history [...].

Bioinspired Approach to Silica Nanoparticle Synthesis Using Amine-Containing Block Copoly(vinyl ethers): Realizing Controlled Anisotropy.

Core-shell polymer-silica hybrid nanoparticles smaller than 50 nm in diameter were formed in the presence of micelles of poly(2-aminoethyl vinyl ether-block-isobutyl vinyl ether) (poly(AEVEm-b-IBVEn)) through the hydrolysis and polycondensation of alkoxysilane in aqueous solution at a mild pH and temperature. The size of the nanoparticles as well as the number and size of the core parts were effectively controlled by varying the molecular weight of the copolymers. The polymers could be removed by calcination to give hollow silica nanoparticles with Brunauer-Emmett-Teller surface areas of more than 500 m2 g-1. Among these, silica nanoparticles formed with poly(AEVE115-b-IBVE40) displayed an anisotropy of single openings in the shell. The use of an alternative copolymer, poly(AEVE-b-2-naphthoxyethyl vinyl ether) (poly(AEVE113-b-ßNpOVE40)), yielded core-shell nanoparticles with less pronounced anisotropy. These results showed that the degree of anisotropy could be controlled by the rigidity of micelles; the micelle of poly(AEVE115-b-IBVE40) was more deformable during silica deposition than that of poly(AEVE113-b-ßNpOVE40) in which aromatic interactions were possible. This bioinspired, environmentally friendly approach will enable large-scale production of anisotropic silica nanomaterials, opening up applications in the field of nanomedicine, optical materials, and self-assembly.

Rheology of Dispersions of High-Aspect-Ratio Nanofibers Assembled from Elastin-Like Double-Hydrophobic Polypeptides.

Elastin-like polypeptides (ELPs) are promising candidates for fabricating tissue-engineering scaffolds that mimic the extracellular environment of elastic tissues. We have developed a "double-hydrophobic" block ELP, GPG, inspired by non-uniform distribution of two different hydrophobic domains in natural elastin. GPG has a block sequence of (VGGVG)5-(VPGXG)25-(VGGVG)5 that self-assembles to form nanofibers in water. Functional derivatives of GPG with appended amino acid motifs can also form nanofibers, a display of the block sequence's robust self-assembling properties. However, how the block length affects fiber formation has never been clarified. This study focuses on the synthesis and characterization of a novel ELP, GPPG, in which the central sequence (VPGVG)25 is repeated twice by a short linker sequence. The self-assembly behavior and the resultant nanostructures of GPG and GPPG were when compared through circular dichroism spectroscopy, atomic force microscopy, and transmission electron microscopy. Dynamic rheology measurements revealed that the nanofiber dispersions of both GPG and GPPG at an extremely low concentration (0.034 wt%) exhibited solid-like behavior with storage modulus G' > loss modulus G" over wide range of angular frequencies, which was most probably due to the high aspect ratio of the nanofibers that leads to the flocculation of nanofibers in the dispersion.

Ring-Like Assembly of Silica Nanospheres in the Presence of Amphiphilic Block Copolymer: Effects of Particle Size.

Block copolymer-mediated self-assembly of colloidal nanoparticles has attracted great attention for the fabrication of a wide variety of nanoparticle arrays. We have previously shown that silica nanospheres (SNSs) 15 nm in diameter assemble into ring-like nanostructures in the presence of amphiphilic block copolymers poly[(2-ethoxyethyl vinyl ether)- block-(2-methoxyethyl vinyl ether)] (EOVE-MOVE) in an aqueous phase. Here, the effects of particle size of SNSs on this polymer-mediated self-assembly are studied systematically using scanning electron microscopy to observe SNSs of seven different sizes between 13 to 42 nm. SNSs of 13, 16, 19, and 21 nm in diameter assemble into nanorings in the presence of EOVE-MOVE. In contrast, larger SNSs of 26, 34, and 42 nm aggregate heavily, form chain-like networks, and remain dispersed, respectively, instead of forming ring-like nanostructures. The assembly trend for 26-42 nm-SNSs agrees with that expected from the increased colloidal stability for larger particles. Time-course observation for the assembled morphology of 16 nm-SNSs reveals that the nanorings, once formed, assemble further into network-like structures, as if the nanorings behave as building units for higher-order assembly. This indicates that the ring-like assembly is a fast process that can proceed onto random colloidal aggregation. Detailed analysis of nanoring structures revealed that the average number of SNSs comprising one ring decreased from 5.0 to 3.1 with increasing the SNS size from 13 to 21 nm. A change in the number of ring members was also observed when the length of EOVE-MOVE varied while the size of SNSs was fixed. Dynamic light scattering measurements and atomic force microscopy confirmed the SNSs/polymer composite structures. We hypothesize that a stable composite morphology may exist that is influenced by both the size of SNSs and the polymer molecular structures.

Beaded nanofibers assembled from double-hydrophobic elastin-like block polypeptides: Effects of trifluoroethanol.

A "double-hydrophobic" elastin-like triblock polypeptide GPG has been constructed by mimicking the localization of proline- and glycine-rich hydrophobic domains of native elastin, a protein that provides elasticity and resilience to connective tissues. In this study, the effects of trifluoroethanol (TFE), an organic solvent that strongly affects secondary structures of polypeptides on self-assembly of GPG in aqueous solutions were systematically studied. Beaded nanofiber formation of GPG, where nanoparticles are initially formed by coacervation of the polypeptides followed by their connection into one-dimensional nanostructures, is accelerated by the addition of TFE at the concentrations up to 30% (v/v), whereas aggregates of nanoparticles are formed at 60% TFE. The concentration-dependent assembly pattern discussed is based on the influence of TFE on the secondary structures of GPG. Well-defined nanofibers whose diameter and secondary structures are controlled by TFE concentration may be ideal building blocks for constructing bioelastic materials in tissue engineering.

Dendritic silica nanoparticles synthesized by a block copolymer-directed seed-regrowth approach.

A facile seed regrowth method is presented for the preparation of a new type of colloidal dendritic silica nanoparticles (DSNPs) with unique Konpeito-like morphology and high surface area (∼400 m(2) g(-1)). Growth of silica nanoprotrusions on the surfaces of colloidal silica nanoparticles proceeds by hydrolysis and polycondensation of tetraethoxysilane (TEOS) in the presence of a PEO-PPO-PEO-type block copolymer (Pluronic F127) under controlled pH conditions. The polymers adsorbed on the seed surface play a crucial role in the formation of DSNPs. DSNPs with controllable size (28-85 nm) and narrow size distributions can be obtained by using monodisperse silica nanoparticles with various sizes as seeds. The surface morphology of DSNPs is tunable by changing the concentration of TEOS. Additionally, novel dendritic silica nanochains are prepared using one-dimensionally assembled silica nanoparticles as the seeds.

Nanoparticle Vesicles with Controllable Surface Topographies through Block Copolymer-Mediated Self-Assembly of Silica Nanospheres.

Silica nanoparticle vesicles (NPVs) with encapsulating capability and surface permeability are highly attractive in nanocatalysis, biosensing, and drug delivery systems. Herein, we report the facile fabrication of silica NPVs composed of a monolayer of silica nanospheres (SNSs, ca. 15 nm in diameter) through the block copolymer-mediated self-assembly of SNSs. The silica NPVs gain different surface topographies, such as raspberry- and brain coral-like topographies, under controlled heat treatment conditions. The vesicular assembly of SNSs is successful with a series of poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide) block copolymers, and the size of NPVs can be tuned by changing their molecular weight. The polymer is easily extracted from the NPVs with their colloidal dispersibility and structural integrity intact. The polymer-free silica NPVs further serve as a reaction vessel and host for functional materials such as tin oxide nanoparticles.

Microphase Separation and Gelation through Polymerization-Induced Self-Assembly Using Star Polyethylene Glycols.

Polymerization-induced self-assembly (PISA) during the synthesis of diblock copolymers has garnered considerable interest; however, architectures beyond diblock copolymers have scarcely been explored. Here, we studied PISA using 4- and 8-arm star polyethylene glycol (PEG), as well as 2-arm (linear) PEG, wherein each terminus of PEG was functionalized with a chain-transfer agent, holding a constant molar mass for each arm. Styrene was polymerized from each PEG terminus through reversible addition-fragmentation chain-transfer (RAFT) polymerization in an ionic liquid (1-butyl-3-methylimidazolium hexafluorophosphate, [BMIM][PF6]), with a total solute concentration of 40 wt %. While the styrene monomer is soluble in [BMIM][PF6], polystyrene is not; thus, self-assembly and cross-linking (gelation) occur. Structural analysis by small-angle X-ray scattering revealed that a relatively ordered microphase-separated structure for PISA was observed. Two-arm PEG-PS formed hexagonally packed cylinders, whereas 4- and 8-arm PEG-PS exhibited hexagonal close-packed spheres and disordered spheres. The dynamics, studied by oscillatory rheology, were also influenced by the number of arms; the 4-arm star block copolymers showed the highest plateau modulus. This study demonstrates that the topology is an important factor in controlling the microphase-separated structure and mechanical properties when preparing gels through PISA.

Near-infrared-II fluorescence/magnetic resonance double modal imaging of transplanted stem cells using lanthanide co-doped gadolinium oxide nanoparticles.

To ensure maximum therapeutic safety and efficacy of stem cell transplantation, it is essential to observe the kinetics of behavior, accumulation, and engraftment of transplanted stem cells in vivo. However, it is difficult to detect transplanted stem cells with high sensitivity by conventional in vivo imaging technologies. To diagnose the kinetics of transplanted stem cells, we prepared multifunctional nanoparticles, Gd2O3 co-doped with Er3+ and Yb3+ (Gd2O3: Er, Yb-NPs), and developed an in vivo double modal imaging technique with near-infrared-II (NIR-II) fluorescence imaging and magnetic resonance imaging (MRI) of stem cells using Gd2O3: Er, Yb-NPs. Gd2O3: Er, Yb-NPs were transduced into adipose tissue-derived stem cells (ASCs) through a simple incubation process without cytotoxicity under certain concentrations of Gd2O3: Er, Yb-NPs and were found not to affect the morphology of ASCs. ASCs labeled with Gd2O3: Er, Yb-NPs were transplanted subcutaneously onto the backs of mice, and successfully imaged with good contrast using an in vivo NIR-II fluorescence imaging and MRI system. These data suggest that Gd2O3: Er, Yb-NPs may be useful for in vivo double modal imaging with NIR-II fluorescence imaging and MRI of transplanted stem cells.

Apatite Formation on α-Tricalcium Phosphate Modified with Bioresponsive Ceramics in Simulated Body Fluid Containing Alkaline Phosphatase.

Bioresponsive ceramics, a new concept in ceramic biomaterials, respond to biological molecules or environments, as exemplified by salts composed of calcium ions and phosphate esters (SCPEs). SCPEs have been shown to form apatite in simulated body fluid (SBF) containing alkaline phosphatase (ALP). Thus, surface modification with SCPEs is expected to improve the apatite-forming ability of a material. In this study, we modified the surface of α-tricalcium phosphate (α-TCP) using methyl, butyl, or dodecyl phosphate to form SCPEs and investigated their apatite formation in SBF and SBF containing ALP. Although apatite did not form on the surface of the unmodified α-TCP in SBF, apatite formation was observed following surface modification with methyl or butyl phosphate. When ALP was present in SBF, apatite formation was especially remarkable on α-TCP modified with butyl phosphate. These SCPEs accelerated apatite formation by releasing calcium ions through dissolution and supplying inorganic phosphate ions, with the latter process only occurring in SBF containing ALP. Notably, no apatite formation occurred on α-TCP modified with dodecyl phosphate, likely because of the low solubility of the resulting calcium dodecyl phosphate/calcium phosphate composites. This new method of using SCPEs is anticipated to contribute to the development of novel ceramic biomaterials.

Diol-linked microporous networks of cubic siloxane cages.

A new class of inorganic-organic hybrid porous materials has been synthesized by a reaction between octa(hydridosilsesquioxane) (H(8)Si(8)O(12)), which has a double-four-ring (D4R) structure, and various diols, such as 1,3-propanediol (PD), 1,4-cyclohexanediol (CHD), and 1,3-adamantanediol (AD). Solid-state (29) Si magic-angle-spinning NMR spectroscopic analysis confirmed that most of the corner Si-H groups reacted with diols to form Si-O-C bonds with retention of the D4R cage. Nitrogen adsorption-desorption studies showed that the products are microporous solids with high BET surface areas (up to ≈580 m(2) g(-1) for CHD- and AD-linked products). If n-alkanediols are used as linkers, the surface area becomes smaller as the number of carbon atoms is increased. The thermal and hydrolytic stability of the products strongly depend on the type of diol linkers. The highest stabilities are found for the AD-linked products, which are thermally stable up to around 400 °C and remain intact even after being soaked in water for 1 day. In contrast, the PD-linked product is easily hydrolyzed in water to give microporous silica. These results offer a new route toward a series of silica-based porous materials with unique structures and properties.

Self-assembly of elastin-mimetic double hydrophobic polypeptides.

We have constructed a novel class of "double-hydrophobic" block polypeptides based on the hydrophobic domains found in native elastin, an extracellular matrix protein responsible for the elasticity and resilience of tissues. The block polypeptides comprise proline-rich poly(VPGXG) and glycine-rich poly(VGGVG), both of which dehydrate at higher temperature but form distinct secondary structures, ß-turn and ß-sheet respectively. In water at 45 °C, the block polypeptides initially assemble into nanoparticles rich in ß-turn structures, which further connect into long (>10 µm), beaded nanofibers along with the increase in the ß-sheet content. The nanofibers obtained are well-dispersed in water, and show thermoresponsive properties. Polypeptides comprising each block component assemble into different morphologies, showing that the conjugation of poly(VPGXG) and poly(VGGVG) plays a role for beaded fiber formation. These results may provide innovative ideas for designing peptide-based materials but also opportunities for developing novel materials useful for tissue engineering and drug delivery systems.

Polymeric Sol-Gel Transition with the Diverging Correlation Length Verified by Small-Angle X-ray Scattering.

Sol-gel transitions of polymers are pivotal phenomena in material science, yet the critical phenomenon of structure during gelation has remained unclear. Here, we investigated the sol-gel transition of a fluorous polymer, poly(vinylidene fluoride-co-hexafluoropropylene), in a blend of two ionic liquids. This system features a quite high amount of cross-linker and binding sites with ion-dipole interactions between the cation and C-F dipoles, thereby facilitating easy exchange of the cross-links. Changing the mixing ratio of the two ionic liquids enabled tuning the ion-dipole interactions and inducing sol-gel transition. Notably, the correlation length and molar mass, obtained by small-angle X-ray scattering, diverged at the gelation point. Moreover, the derived critical exponents (ν = 0.85 ± 0.05) aligns remarkably well with the prediction from percolation theory (ν = 0.88). To our knowledge, this is the first report on the evident divergence during polymeric gelation by small-angle scattering and the verification of the critical exponents of the percolation theory.

Biological properties of self-assembled nanofibers of elastin-like block polypeptides for tissue-engineered vascular grafts: platelet inhibition, endothelial cell activation and smooth muscle cell maintenance.

Strategic materials design is essential for the development of small-diameter, tissue-engineered vascular grafts. Self-assembled nanofibers of elastin-like polypeptides represent promising vascular graft components as they replicate the organized elastin structure of native blood vessels. Further, the bioactivity of nanofibers can be modified by the addition of functional peptide motifs. In the present study, we describe the development of a novel nanofiber-forming elastin-like polypeptide (ELP) with an arginine-glutamic acid-aspartic acid-valine (REDV) sequence. The biological characteristics of the REDV-modified ELP nanofibers relevant to applications in vascular grafting were compared to ELP without ligands for integrin, ELP with arginine-glycine-aspartic acid (RGD) sequence, collagen and cell culture glass. Among them, REDV-modified ELP nanofibers met the preferred biological properties for vascular graft materials, i.e. (i) inhibition of platelet adhesion and activation, (ii) endothelial cell adhesion and proliferation and (iii) maintenance of smooth muscle cells in a contractile phenotype to prevent cell overgrowth. The results indicate that REDV-modified ELP nanofibers represent promising candidates for the further development of small-diameter vascular grafts.

In Vivo Real-Time Quantum Dots Imaging to Track Transplanted Adipose Stem Cells in Different Inflammatory States of Acute Liver Failure Mice.

Stem cell therapy plays an important role in regenerative therapy; however, there is little information on the in vivo dynamics of transplanted stem cells and the influence of the inflammation of affected tissues or organs on these dynamics. In this study, we revealed real-time dynamics of transplanted adipose tissue-derived stem cells (ASCs) and the influence of the inflammatory states on these dynamics in acute liver failure mice. Quantum dots (QDs) labeling did not affect the cytokine profile of ASCs, and intravenously transplanted ASCs labeled with QDs could be detected in real time with high efficiency without laparotomy. Until 30 min after ASC transplantation, no marked differences in the behavior or accumulation of transplanted ASCs in the liver were observed among the three groups with different degrees of liver damage (normal, weak, and strong). However, significant differences in the engraftment rate of transplanted ASCs in the liver were observed among the three groups from 4 h after transplantation. The engraftment rate was inversely correlated with the extent of the liver damage. These data suggested that QDs are useful for in vivo real-time imaging of transplanted cells, and the inflammatory state of tissues or organs may affect the engraftment rate of transplanted cells.