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Titanium dioxide (TiO2) photofunctionalization has been demonstrated as an effective surface modification method for the osseointegration of implants. However, the insufficient understanding of the mechanism underlying photofunctionalization limits its clinical applications. Here, we report an ultraviolet (UV) radiant energy-dependent functionalization on TiO2 nanodots (TN) surfaces. We found the cell adhesion, proliferation, and osteogenic differentiation gradually increased with the accumulation of UV radiant energy (URE). The optimal functionalizing treatment energy was found to be 2000 mJ/cm2, which could regulate cell-specific behaviors on TN surfaces. The enhanced cell behaviors were regulated by the adsorption and functional site exposure of the extracellular matrix (ECM) proteins, which were the result of the surface physicochemical changes induced by the URE. The correlation between the URE and the reconstruction of surface hydroxyl groups was considered as an alternative mechanism of this energy-dependent functionalization. We also demonstrated the synergistic effects of FAK-RHOA and ERK1/2 signaling pathways on mediating the URE-dependent cell behaviors. Overall, this study provides a novel insight into the mechanisms of photofunctionalization, guiding the design of implants and the clinical practice of photofunctionalization.

Light-induced cell harvest shows much potential in in vitro cell culture. In this work, a light-responsive monolayer graphene (Gr)/titanium dioxide nanodot (TN) film is designed and used for light-induced cell harvest. It is found that after 20 min of 365 nm UV or 450 nm visible light illumination, different types of cells could be detached from the surface effectively. The highest cell detachment ratio reaches about 95%. The mechanism of such a cell detachment is contributed to light illumination generates charge accumulation, which, in turn, changes the conformation of the extracellular matrix protein molecules adsorbed to a more disordered state, and eventually leads to the cells detachment. Such UV and visible light responsive Gr/TiO2 film could be a good candidate for a surface with light-induced cell detachment property.

Mechanical stimulation has been considered to be critical to cellular response and tissue regeneration. However, harnessing the direction of mechanical stimulation during osteogenesis still remains a challenge. In this study, we designed a series of novel magnetized collagen coatings (MCCs) (randomly or parallel-oriented collagen fibers) to exert the anisotropic mechanical stimulation using oriented magnetic actuation during osteogenesis. Strikingly, we found the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) were significantly up-regulated when the direction of magnetic actuation was parallel to the randomly-oriented collagen coating surface, in contrast to the down-regulated capacity under the perpendicular magnetic actuation. Moreover, further exerting a parallel mechanical stimulation along the parallel-oriented collagen coating, which cells have been oriented by the oriented collagens, were not only able to up-regulate the osteogenic differentiation of BMSCs but also promote the new bone formation during osteogenesis in vivo. We also demonstrated the anisotropic magneto-mechanical stimulation for the osteogenic differences might be attributed to the stretching or bending tensile status of collagen fibers controlled by the direction of magnetic actuation, driving the α5β1-dependent integrin signaling cascade. This study therefore got insight of understanding the directional mechanical stimulation on osteogenesis, and also paved a way for sustaining regulation of the biomaterials-host interface.

Natural extracellular matrices (ECMs) are three-dimensional (3D) and multi-scale hierarchical structure. However, coatings used as ECM-mimicking structures for osteogenesis are typically two-dimensional or single-scaled. Here, we design a distinct quasi-three-dimensional hierarchical topography integrated of density-controlled titania nanodots and nanorods. We find cellular pseudopods preferred to anchor deeply across the distinct 3D topography, dependently of the relative density of nanorods, which promote the osteogenic differentiation of osteoblast but not the viability of fibroblast. The in vivo experimental results further indicate that the new bone formation, the relative bone-implant contact as well as the push-put strength, are significantly enhanced on the 3D hierarchical topography. We also show that the exposures of HFN7.1 and mAb1937 critical functional motifs of fibronectin for cellular anchorage are up-regulated on the 3D hierarchical topography, which might synergistically promote the osteogenesis. Our findings suggest the multi-dimensions and multi-scales as vital characteristic of cell-ECM interactions and as an important design parameter for bone implant coatings.

A facile strategy is needed for accurate time-space supply of suitable growth factors or drugs. Polypyrrole (PPy) was able to carry almost all kinds of negatively charged biomolecules through anodizing method, which made it an appropriate way for codeposition of multiple molecules. The difference in the conjugation between different molecules and PPy makes it possible for selective release when the redox state of PPy changes. In this work, bovine serum albumin (BSA) and heparin (Hep) were chosen to be the model molecules in view of their differences in the level of electronegativity and molecular weight. Double-layer deposition method was used to improve the biocompatibility of PPy/BSA/Hep film. It was found the content of BSA and Hep in the film can be controlled by regulating deposition current and time. BSA release was facilitated under positive voltage and then promote the proliferation of preosteoblasts, while Hep release was promoted under negative voltage and enhance cell differentiation. Our work provides a dual-molecule model in PPy for selective release and further explores the mechanism of release selectivity, this discovery has potential applications in tissue engineering and regenerative medicine.

The surface electric potential of biomaterials has been extensively proven to play a critical role in stem cells' fate. However, there are ambiguous reports on the relation of stem cells' osteogenic capacity to surface potential characteristics (potential polarity and intensity). To address this, we adopted a surface with a wide potential range and both positive/negative polarity in a comprehensive view to get insight into surface potential-regulating cellular osteogenic differentiation. Tb

In this work, hydrothermal treatment and ultraviolet illumination (254 nm) were utilized to regulate the surface hydroxyls of titanium dioxide (TiO2) nanodots films. The effects on light-induced cell detachment behaviors were also investigated and discussed. Scanning electron microscopy, Raman, X-ray photoelectron spectroscopy and Circular dichroism were used to characterize the surface morphology, crystalline phase, surface composition and adsorption conformation of protein molecules. It was found that a combined process of ultraviolet illumination followed by hydrothermal treatment not only promoted cells adhesion but also showed the highest efficiency in light induced cell detachment. The reason is ascribed to that such process promotes the formation of terminal hydroxyl groups in TiO2 surface, and subsequently affect the adsorption conformation of protein molecules. This study indicated that such treatment could effectively modulate the contents of surface hydroxyl groups in different states. That shows much potential in optimizing the biological performance of TiO2 based biomaterials.

This study presents a convenient and versatile way to prepare functionalized composite polydopamine/titanium dioxide (PDA/TiO2) film on polystyrene (PS). First, polystyrene substrate was immersed in dopamine chloride solution, and then collosol containing TiO2 and water was spun on it, to produce uniform, continuous PDA/TiO2 composite films. The thickness of film was controllable by adjustment of the spin speed. It was found that the films were strongly adhered on the PS substrate, with peel strength and shear strength of 2.78 MPa and 37.78 MPa, respectively. After 20 min of ultraviolet (365 nm) illumination, over 90% of fibroblasts and 77% of osteoblasts detached from the PDA/TiO2 composite film. Additionally, the detached cells showed good viability, allowing further culture and applications. This preparation method could be widely applied for cell and cell sheet harvesting directly from PS-based culture wares.

Electrical stimulation has been proved to be critical to regulate cell behavior. But, cell behavior is also susceptible to multiple parameters of the adverse interferences such as surface current, electrochemical reaction products, and non-uniform compositions, which often occur during direct electric stimulation. To effectively prevent the adverse interferences, a novel piezoelectric poly(vinylidene fluoride-trfluoroethylene)(P(VDF-TrFE)) layer was designed to coat onto the indium tin oxide (ITO) planar microelectrode. We found the electrical stimulation was able to regulate the osteogenic differentiation of mesenchymal stem cells (MSCs) through calcium-mediated PKC signaling pathway. Meanwhile, the surface charge of the designed P(VDF-TrFE) coating layer could be easily controlled by the pre-polarization process, which was demonstrated to trigger integrin-mediated FAK signaling pathway, finally up-regulating the osteogenic differentiation of MSCs. Strikingly, the crosstalk in the downstream of the two signaling cascades further strengthened the ERK pathway activation for osteogenic differentiation of MSCs. This P(VDF-TrFE) layer coated electrical stimulation microelectrodes therefore provide a distinct strategy to manipulate multiple-elements of biomaterial surface to regulate stem cell fate commitment.

Well-aligned collagen nanofibers are crucial in engineering bioinspired regenerative strategies, such as bone, muscle and cornea. However, keeping the natural bioactive of collagen and controlling its orientation in a coating still remain a challenge. Here we present a novel magnetically assisted electrochemical technique to deposit type-I collagen nanofibers with high alignment onto titanium. The magnetic assistance involved mainly the incorporation of iron oxide nanoparticles (IOPs) and the application of an external magnetic field during the electrochemical deposition. The combination of IOPs with the collagen nanofibrils in electrolyte endowed the nanofibrils with magnetism, which forced the collagen nanofibrils to be straightened and assembled into aligned nanofibers under magnetic field during electrodeposition. The influence of the applied magnetic field on orientational order of the collagen nanofibers in the coatings extended to drying stage. The aligned collagen coatings demonstrated to favorably guide the bone marrow mesenchymal stem cells (BMSCs) grow in the form of elongated morphology, which promoted the cellular osteogenic differentiation dramatically. The present magnetically assisted electrodeposition could emerge as an attractive approach to fabrication of aligned nanofibers on substrates for subsequent uses such as bone tissue engineering.

Loading of an appropriate amount of rhBMP-2 and avoiding its “burst-release” are key challenges for upgrading the biological performance of thin bioactive coatings on metal implants. In this study, we adopted incorporation of chitosan nanospheres into thin mineralized collagen coatings to enhance rhBMP-2 loading and improve releasing behavior based on the good affinity of chitosan for proteins and the large surface area of nanospheres. We realized the incorporation process by electrophoretic injection. Using chitosan nanospheres, we were able to increase the rhBMP-2 loading amount in the thin coating by 2.7-fold (from 446 ng cm−2 to 1186 ng cm−2), and showed that the rhBMP-2 exhibited sustained release behavior. MC3T3-E1 cells cultured on the rhBMP-2/chitosan nanosphere-incorporated thin coatings (Col/Cs/BMP) showed good cell attachment and proliferative behavior, and high levels of differentiation and mineralization. In in vivo tests, spiral CT analysis and histological observations demonstrated that Col/Cs/BMP coatings on metal implants were able to increase bone density and accelerate new bone growth after implantation for 4 to 8 weeks, and the boundary between host bones and new bones disappeared after implantation for 8 weeks. The pull-out tests further confirmed that the Col/Cs/BMP coatings could significantly enhance osseointegration. The present results indicate that incorporation of chitosan nanospheres into thin coatings is an effective way to enhance the loading amount properly, improve the release behavior of rhBMP-2 and finally accelerate the osseointegration process.

Surface-mediated gene delivery has attracted more and more attentions in biomedical research and applications because of its characteristics of low toxicity and localized delivery. Herein, a novel visible-light-regulated, surface-mediated gene-delivery platform is exhibited, arising from the photoinduced surface-charge accumulation on silicon. Silicon with a pn junction is used and tested subsequently for the behavior of surface-mediated gene delivery under visible-light illumination. It is found that positive-charge accumulation under light illumination changes the surface potential and then facilitates the delivery of gene-loaded carriers. As a result, the gene-expression efficiency shows a significant improvement from 6% to 28% under a 10 min visible-light illumination. Such improvement is ascribed to the increase in surface potential caused by light illumination, which promotes both the release of gene-loaded carriers and the cellular uptake. This work suggests that silicon with photovoltaic effect could offer a new strategy for surface-mediated, gene-delivery-related biomedical research and applications.

Graphene (Gr)/poly(vinylidenefluoride-co-trifluoroethylene) (P(VDF-TrFE)) composite films were annealed by the photothermal effect that produced between near-infrared laser and graphene. Raman spectra, X-ray Diffraction (XRD), Fourier-Transformed Infrared Spectroscopy (FTIR), Differential scanning calorimetry (DSC) are used to characterize the crystalline state of Gr/P(VDF-TrFE) films. Further, piezoelectric coefficient d33 were to test polarization performance. Finally, the Bovine serum albumin (BSA) adsorption shows that annealing and polarization of Gr/P(VDF-TrFE) films are important for protein adsorption.

Three-dimensional (3D) printing technology has been widely used to fabricate of various titanium and its alloy implants. However, engineering the 3D printing nanoscaled feature to realize a hierarchical micronano structured surface topography still remains a challenge. On one hand, enhanced bioactivity is always expected on micronano-hybrid biomimetic topography; on the other hand, a typical functional protein in extracellular matrix (ECM) is nanoscaled; therefore, nanoscaled features might affect its binding to specific receptor and subsequent cell response. Here, we engineered a novel hierarchical structure with microparticles and rutile TiO2 nanorods topography that fabricated by 3D printing of pure titanium followed by a hydrothermal process. Although there was no difference on the microscaled feature before/after nanonization, cellular behaviors including adhesion, proliferation, and osteogenic differentiation of mesenchymal stem cells (MSCs) were significantly upregulated on the hierarchical microna...

Mechanical stimuli at the bone-implant interface are considered to activate the mechanotransduction pathway of the cell to improve the initial osseointegration establishment and to guarantee clinical success of the implant. However, control of the mechanical stimuli at the bone–implant interface still remains a challenge. In this study, we have designed a strategy of a magnetically responsive coating on which the mechanical stimuli is controlled because of coating deformation under static magnetic field (SMF). The iron oxide nanoparticle/mineralized collagen (IOP-MC) coatings were electrochemically codeposited on titanium substrates in different quantities of IOPs and distributions; the resulting coatings were verified to possess swelling behavior with flexibility same as that of hydrogel. The relative quantity of IOP to collagen and the IOP distribution in the coatings were demonstrated to play a critical role in mediating cell behavior. The cells present on the outer layer of the distributed IOP-MC (O-IOP-MC) coating with a mass ratio of 0.67 revealed the most distinct osteogenic differentiation activity being promoted, which could be attributed to the maximized mechanical stimuli with exposure to SMF. Furthermore, the enhanced osteogenic differentiation of the stimulated MC3T3-E1 cells originated from magnetically actuated mechanotransduction signaling pathway, embodying the upregulated expression of osteogenic-related and mechanotransduction-related genes. This work therefore provides a promising strategy for implementing mechanical stimuli to activate mechanotransduction on the bone–implant interface and thus to promote osseointegration. Statement of Significance The magnetically actuated coating is designed to produce mechanical stimuli to cells for promoting osteogenic differentiation based on the coating deformation. Iron oxide nanoparticles (IOPs) were incorporated into the mineralized collagen coatings (MC) forming the composite coatings (IOP-MC) with spatially distributed IOPs, and the IOP-MC coatings with outer distributed IOPs (O-IOPs-MC) shows the maximized mechanical stimuli to cells with enhanced osteogenic differentiation under static magnetic field. The upregulated expression of the associated genes reveals that the enabled mechanotransduction signaling pathway is responsible for the promoted cellular osteogenic differentiation. This work therefore provides a promising strategy for implementing mechanical stimuli to activate mechanotransduction on the bone–implant interface to promote osseointegration.

In the present study, TiO2/ZnO composite nanodot films were prepared and the effects of Zn incorporation on light-induced cell detachment were investigated. The nanodots films, which were successfully synthesized by phase-separation-induced self-assembly method, were characterized on the morphology, composition, microstructure, and other properties, and evaluated on cell compatibility and cell detachment performances as well. Live-dead staining was used to study the viability of cell sheet detached by light illumination. Results shows that with the increasing of introduced Zn, the band gap widened and the absorbance in UV region increased, while the crystallinity and performance of light-induced hydrophilicity weakened. All the nanodots films showed good cell compatibility and cell detachment performance induced by light. The nanodots film which had a Zn/Ti molar ratio of 0.03 showed the highest detachment ratio of 91.0% after 20 min ultraviolet illumination. The prepared TiO2/ZnO composite nanodots films could be helpful in optimizing light-induced cell detachment behavior.

Light-induced surface potential have been demonstrated as an effective bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation regulator. However, traditional bone repair implants almost were weak or no light-responsive. Fortunately, surface modification was a feasible strategy to realize its light functionalization for bone implants. Herein, a graphene oxide (GO)/titanium dioxide (TiO2) nanodots composite coating on the surface of titanium (Ti) implant was constructed, and GO was reduced to reduced graphene oxide (rGO) with the method of UV-assisted photocatalytic reduction. After rGO deposited on the surface of TiO2, a heterojunction formed at the interface of rGO and TiO2. With visible light illumination, positive charges accumulated on the surface of rGO/TiO2 film, and performed as a positive surface potential change. The light-induced surface potential which was generated under proper light intensity is harmless to the cell adhesion and proliferation behavior, but presented a good BMSCs osteogenic differentiation promoting effect, and the activation of the voltage-gated calcium channels through surface potential and the promotion of the adsorption of osteogenic growth factors could be the reason. This work given a new insight of the modification for Ti implant with a light-induced surface potential, and shows potential application for bone regeneration on the clinical practice through light stimulation.

The combination of bone marrow-derived mesenchymal stem cells (BMSCs) and biological scaffolds has been demonstrated to be a promising strategy for bone regeneration. However, this method does not result in satisfactory bone regeneration, because the BMSCs are dispersed in the biological scaffolds. The current study developed a new bone regeneration system, which combines synthetic porous three-dimensional scaffolds of β-TCP/COL-I composite with cultured osteogenic sheets of BMSCs. Activity of alkaline phosphatase (ALP), a marker of bone regeneration, was assayed in vitro using enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reaction. In vivo bone regeneration was assayed in male nude mice. The study samples were BMSC sheet, scaffold/scattered BMSCs, scaffold/BMSC sheet, and scaffold alone. The samples were implanted dorsally in the mice. In vitro analysis showed that β-TCP/COL-I scaffold combined with BMSC sheets significantly upregulated both gene expression and protein levels of ALP, osteocalcin, and osteopontin. Histological and micro-computed tomography showed that the only implants that demonstrated new bone formation after 4 weeks were scaffold/BMSC sheet implants. These results underscore the crucial requirement of a synergistic effect of β-TCP/COL-I scaffolds and BMSC sheets. This could be a promising novel strategy for bone tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2037-2045, 2018.

The topography at the micro/nanoscale level for biomaterial surfaces has been thought to play vital roles in their interactions with cells. However, discovering the interdisciplinary mechanisms underlying how cells respond to micro-nanostructured topography features still remains a challenge. In this work, ∼37 μm 3D printing used titanium microspheres and their further hierarchical micro-nanostructured spheres through hydrothermal treatment were adopted to construct typical model surface topographies to study the preosteoblastic cell responses (adhesion, proliferation, and differentiation). We here demonstrated that not only the hierarchical micro-nanostructured surface topography but also their distribution density played critical role on cell cytocompatibility. The microstructured topography feature surface with middle-density distributed titanium microspheres showed significantly enhanced cell responses, which might be attributed to the better cellular interaction due to the cell aggregates. However, the hierarchical micro-nanostructured topography surface, regardless of the distribution density of titanium microspheres, improved the cell-surface interactions because of the enhanced initial protein adsorption, thereby reducing the cell aggregates and consequently their responses. This work, therefore, provides new insights into the fundamental understanding of cell-material interactions and will have a profound impact on further designing micro-nanostructured topography surfaces to control cell responses.

Biomimetic mineralization of nanocalcium phosphate (CaP) on metal oxide surfaces has gained great interest because of their relevance to osseointegration performance of implant materials. However, precisely controlling the nucleation behavior of mineralized nano-CaP on metal oxide at selective sites still remains a challenge. Here, we demonstrate a phenomenon on facet-specific mineralization on anatase TiO2 polyhedral microcrystals organized by two facets of {101} and {001} in complete cell culture medium: nano-CaP covers up {101} facets, while there are a few on {001} facets. The comparative experimental results indicate that the preadsorbed fetal bovine serum (FBS) protein on {001} facets might play a barrier role in preventing sequential nucleation of nano-CaP. This work thus provides insight into the understanding of mineralization on metal oxides, and a way to control the mineralization.

Stem cells in contact with materials are able to sense their surface features, integrate extracellular matrix (ECM) protein cues through a signal transduction pathway, and ultimately direct cell fate decisions. However, discovering the interdisciplinary mechanisms of how stem cells respond to inherent material surface features still remains a challenge due to the complex, multicomponent signaling milieu present in the ECM environment. Here, we demonstrate that the fate of human mesenchymal stem cells (hMSCs) can be regulated by the inherent physical cue of the material surface down to atomic-scale features. hMSCs on a TiO-terminated SrTiO3 {110} substrate tend to differentiate into specific lineage cells (osteoblast, chondrocyte, adipocyte), whereas on a TiO2-terminated SrTiO3 {100} substrate they are prone to maintain pluripotency. The experimental observations and molecular dynamics simulations indicate that the distinct conformations of the initially adsorbed serum albumin and fibronectin proteins acti...

A series of Ni1-xCux/Sm-doped ceria (Ni1-xCux/SDC) anodes have been prepared through introducing a soluble pore former with the co-pressing and co-sintering process. Uniform hierarchical porous microstructures are formed in Ni0.9Cu0.1/SDC anode with interconnected large pores of 2–5 μm and 100–300 nm small pores on the wall. The solid oxide fuel cell (SOFC) based on such anode exhibits exceptional electrochemical catalytic activity for dry CH4 oxidation and a maximum power density of 379 mW cm−2 is acquired at 600 °C. Durability test results show only 2.4% power density drop is observed after 72 h operation under a constant cell voltage of 0.5 V. The results have demonstrated that the optimization of anode microstructures is an effective way to improve the performance and long-term stability of Ni1-xCux alloy-based anode-supported SOFC.

Light-induced cell detachment shows much potential in in vitro cell culture and calls for high-performance light-responsive films. In this study, a smooth and dense SiO2/TiO2 nanocomposite thin film with thickness of around 250 nm was first fabricated on H2O2 treated polystyrene (PS) substrate via a low-temperature sol–gel method. It was observed that the film could well-adhere on the PS surface and the bonding strength became increasingly high with the increase of SiO2 content. The peeling strength and shear strength reached 3.05 and 30.02 MPa, respectively. It was observed the surface of the film could transform into superhydrophilic upon 20 min illumination of ultraviolet with a wavelength of 365 nm (UV365). In cell culture, cells, i.e., NIH3T3 and MC3T3-E1 cells, cultured on SiO2/TiO2 nanocomposite film were easily detached after 10 min of UV365 illumination; the detachment rates reached 90.8% and 88.6%, respectively. Correspondingly, continuous cell sheets with good viability were also easily obtaine...

Titanium (Ti) and tantalum (Ta) metals have been widely used as implants for their favorable mechanical features and good biocompatibility. However, the results on their osteogenic capacity have been conflicting due to the synergistic effects of complex and multiple material surface features (such as topography, surface chemistries etc.) on cellular behaviors. Here, we directly compare the osteogenic response of mesenchymal stem cells (MSCs) to Ti and Ta metal surfaces with alterable surface hydroxyl groups. Although no difference was found on both surface topographies, cellular adhesion, proliferation, and the expression of osteogenic-related markers were upregulated with the increasing amount of surface hydroxyl groups (-OH) after ultraviolet (UV) light treatment. Moreover, Ti showed better effects in promoting osteogenic differentiation of MSCs than Ta before UV light treatment, but demonstrated the opposite after UV light treatment. These results might be attributed to the comparative quantity of the distinct type of surface hydroxyl groups (bridging-OH and terminal-OH), which regulated the conformation of the initial protein adsorption and subsequent cellular behaviors. Our results demonstrate the central role of the surface hydroxyl groups in mediating cell-material interactions and implicate this interface as helping in optimizing osteointegration of Ti and Ta based orthopaedic and dental implants.

Early vascularization in bone defects has been considered to play a critical role in the bone regeneration process. Although mesenchymal stem cells (MSCs) co-cultured with endothelial cells (ECs) have attracted the most attention in strategies that seek to achieve vascularized bone, it still remains a challenge to achieve a prevascularized construct in vitro that can be translated conveniently. Here, we provided a strategy of engineering a transferable prevascularized MSC–EC composite cell sheet to promote the vascular-like network formation for bone tissue engineering. We co-cultured human mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVECs) on a distinct light-responsive TiO2 nanodots film. Various cell ratios of MSC–EC and culture mediums were explored to achieve the optimal angiogenesis capacity. The prevascularized MSC–EC composite cell sheet was then detached as an intact and confluent cell layer by a simple light treatment, and showed high viability and 3D network formation surrounded by mesenchymal stem cells. This light-induced cell sheet technology therefore realized a novel transferable prevascularized MSC–EC composite cell sheet, and will have a profound impact on further strategies for designing in-bone tissue engineering.

Alkali treatment has been widely used for the surface modification of Ti and Ti alloys for clinical applications. However, the mechanism underlying the effects of the alkali-treated Ti surface on the cell response still needs to be explored. In this study, we demonstrated that the cell responses on a H2Ti3O7 nanowire film, normally titanate generated on a Ti surface via alkali treatment and ion exchange, were sensitive to the surface hydroxyl groups of the H2Ti3O7 nanowire films, i.e. the total amount as well as comparative ratio of the distinct type of surface hydroxyl groups (bridging-OH and terminal-OH). The surface hydroxyl groups of H2Ti3O7 nanowires were further controlled via heat treatment to produce anatase TiO2 nanowire films. Although there was no difference in both topographies, cells on a H2Ti3O7 nanowire film showed more elongated shape than those on an anatase nanowire film. Moreover, the expression of ALP of cells on H2Ti3O7 upregulated as compared to that on the anatase nanowire film at day 4, suggesting enhanced osteogenic capacity at an early stage. These results could be attributed to the difference in the distinct ratio of the terminal hydroxyl groups to the bridging hydroxyl groups, which was 0.42 for the H2Ti3O7 nanowire film and 0.75 for the anatase nanowire film. It appeared that the bridging hydroxyl groups on H2Ti3O7 were efficient in attracting Ca2+, which influenced the cell morphology and further upregulated the early differentiation.

Graphene (Gr) presents promising applications in regulating the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Light illumination is regarded as a spatiotemporally controllable, easily applicable, and noninvasive mean to modulate material responses. Herein, Gr-transferred silicon (Gr/Si) with a Schottky junction is utilized to evaluate the visible-light-promoted osteogenic differentiation of BMSCs. Under light illumination, light-induced charges, owing to the formation of the Schottky junction at the interface of Gr and Si, accumulated on the surface and then changed the surface potential of Gr/Si. The Schottky junction and surface potential at the interface of Gr and Si was measured by photovoltaic test and scanning Kelvin probe microscopy. Alkaline phosphatase (ALP) activity and quantitative real-time polymerase chain reaction (PCR) measurement showed that such variations of surface improved the osteogenic differentiation of BMSCs, and the activation of the voltage-gated calcium channels through surface potential and accumulation of cytosolic Ca2+ could be the reason. Moreover, X-ray photoelectron spectroscopy characterization showed that surface charge could also affect BMSCs differentiation through the promotion or inhibition of the adsorption of osteogenic growth factors. Such light-promoted osteogenic differentiation of BMSCs on Gr/Si may have huge potential for biomedical materials or devices for bone regeneration application.

It is well known that three-dimensional (3D) printing is an emerging technology used to produce customized implants and surface characteristics of implants, strongly deciding their osseointegration ability. In this study, Ti alloy microspheres were printed under selected rational printing parameters in order to tailor the surface micro-characteristics of the printed implants during additive manufacturing by an in situ, controlled way. The laser path and hatching space were responsible for the appearance of the stripy structure (S), while the bulbous structure (B) and bulbous&ndash, stripy composite surface (BS) were determined by contour scanning. A nano-sized structure could be superposed by hydrothermal treatment. The cytocompatibility was evaluated by culturing Mouse calvaria-derived preosteoblastic cells (MC3T3-E1). The results showed that three typical microstructured surfaces, S, B, and BS, could be achieved by varying the 3D printing parameters. Moreover, the osteogenic differentiation potential of the S, B, and BS surfaces could be significantly enhanced, and the addition of nano-sized structures could be further improved. The BS surface with nano-sized structure demonstrated the optimum osteogenic differentiation potential. The present research demonstrated an in situ, controlled way to tailor and optimize the surface structures in micro-size during the 3D printing process for an implant with higher osseointegration ability.

In this work, mineralized collagen coatings with different loading quantity of bovine serum albumin (BSA) were prepared via in situ electrochemical deposition on titanium substrate. The microstructure and BSA loading quantity of the coatings could be controlled by the electrochemical deposition parameters, such as deposition potential, BSA concentration and its adding sequence in the electrolyte. The BSA loading quantity in the coatings was obtained in the range of 0.0170-0.173mg/cm(2), enhancing the cell adhesion and proliferation of the coatings with the simultaneous release. The distinct release behaviors of BSA were attributed to their gradient distribution with different mineralization degrees, which could be adjusted by the deposition process. These results suggest that in situ electrochemical deposition is a promising way to incorporate functional molecules into the mineralized collagen coatings and the mineralized BSA/collagen coatings are highly promising for improving the rhBMP-2 loading capability (1.8-fold).

Invited for this month's cover is the interdisciplinary research group of Prof. Kui Cheng from Zhejiang University, China. The cover picture shows a schematic figure of carbon quantum dots incorporated as a sensitizer into TiO2 films to regulate the light-induced cell-detachment performance. Read the full text of the article at 10.1002/cplu.201600202.

Cellular responses are strongly sensitive to surface structure, so the optimization of the structures is essential in biomaterial research. In this work, the exposed nanorod-heights in TiO2 nanorod films were adjusted for enhancing cellular responses. The adjustment was realized by incorporating mesoporous bioactive glass (MBG) into the nanorod films via a sol–gel method. The exposed nanorod-heights in the films could be changed from the original ∼300 nm to ∼200 nm and ∼100 nm. The cellular responses on the nanostructured surfaces were evaluated through culturing mesenchymal stem cells (MSCs). The results showed that the films with shortened nanorod-heights had better cellular responses and could accelerate osteogenic differentiation and mineralization, and the films with 100 nm nanorod-height provided the best surface for cell growth. This is attributed to the nanostructure with the shortened nanorod-heights being well recognized by the cells, consequently the cells grew with a faster osteogenic differentiation through a strengthened BMP-smads signal pathway.

High performance of biomaterial surfaces provides a sound basis to mediate cellular growth behavior. In this work, we attempted to incorporate both positive and negative magnetostriction particles of CoFe2O4 (CFO) and TbxDy1−xFe2 alloy (TD) into piezoelectric poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) for forming high magnetoelectric effect films, on which osteogenic differentiation could be dynamically mediated by a magnetic-field-induced surface potential (φME).The negatively poled film with TD/CFO volume ratio of 1:4 (1T4C) showed a highest magnetoelectric effect with φME of −171 mV at 2800 Oe. Compared with CFO/P(VDF-TrFE) and TD/P(VDF-TrFE) films, the φME increased about 213% and 173%, respectively. This could result from that P(VDF-TrFE) dipole domains receive a larger off-axial stress caused by the distribution characteristic of CFO and TD in P(VDF-TrFE), consequently to facilitate P(VDF-TrFE) dipole domain rearrangement. When MSCs were cultured on 1T4C film for 7 or 14 days, the magnetic actuation was setup to begin at the 4th or 8th day after the culture. The 7-day osteogenic differentiation was hardly affected for magnetic actuation at 4th day, moreover, the 14-day differentiation was significantly enhanced for magnetic actuation at 8th day. The enhancement appears just at a relatively late period of the cell growth, probably because the cells need a steady change in cell membrane potential to disassociate pairs of β-catenin and E-cadherin and activate osteogenic-related signaling pathway. This work could provide an alternative way to promote performance for magnetoelectric materials, and get insight into understanding of interactions of surface potential with cells.

Surface nanotopography and bioactive ions have been considered to play critical roles on the interactions of biomaterials with cells. In this study, a TiO2 nanorod film incorporated with Zn-containing bioactive glass (TiO2/Zn-BG) was prepared on tantalum substrate, trying to evaluate the synergistic effects of nanotopograpgy and bioactive ions to promote cellular osteogenic differentiation activity. The expression of osteogenic-related genes, ALP as well as the ECM mineralization on TiO2/Zn-BG film were significantly upregulated compared to that of the film without TiO2 nanorod nanostructure (Zn-BG) or without Zn (TiO2/BG). Moreover, a much low Zn2+ release level on TiO2/Zn-BG film was beneficial to promote the osteogenesis, which could be ascribed to that a semi-closed space established by TiO2 nanorods with adhered cells provided an appropriate micro-environment that facilitated Zn2+ adsorption.

Extracellular matrix (ECM) provides a dynamic and complex environment to determine the fate of stem cells. In this work, light harvested cell sheets were treated with paraformaldehyde or ethanol, which eventually become ECM. Such ECM was then immobilized on titanium substrates via polydopamine chemistry. Their effects on bone marrow mesenchymal stromal cells (BMSCs) behaviors were investigated. It was found that paraformaldehyde-treated ECM coating (PT-ECM) showed a well-maintained microstructure, whereas that of ethanol-treated (ET-ECM) was completely changed. As a result, different amide structures and distributions of ECM components, such as laminin and collagen I, were exhibited. Alkaline phosphatase activity, osteocalcin secretion, related gene expression, and mineral deposition were evaluated for BMSCs cultured on both ECM coatings. PT-ECM was demonstrated to promote osteogenic differentiation much more efficiently than that of ET-ECM. That is ascribed to the preservation of native ECM milieu of PT-ECM. Such ECM acquirement and immobilization method could establish surfaces being able to direct stem cell responses on various materials. That shows promising potential in bone tissue engineering and other related biomedical applications.

The binding of cell integrins to proteins adsorbed on the material surface is a highly dynamic process critical for guiding cellular responses. However, temporal dynamic regulation of adsorbed proteins to meet the spatial conformation requirement of integrins for a certain cellular response remains a great challenge. Here, an active CoFe2O4/poly(vinylidene fluoride-trifluoroethylene) nanocomposite film, which was demonstrated to be an obvious surface potential variation (Δ V ≈ 93 mV) in response to the applied magnetic field intensity (0-3000 Oe), was designed to harness the dynamic binding of integrin-adsorbed proteins by in situ controlling of the conformation of adsorbed proteins. Experimental investigation and molecular dynamics simulation confirmed the surface potential-induced conformational change in the adsorbed proteins. Cells cultured on nanocomposite films indicated that cellular responses in different time periods (adhesion, proliferation, and differentiation) required distinct magnetic field intensity, and synthetically programming the preferred magnetic field intensity of each time period could further enhance the osteogenic differentiation through the FAK/ERK signaling pathway. This work therefore provides a distinct concept that dynamically controllable modulation of the material surface property fitting the binding requirement of different cell time periods would be more conducive to achieving the desired osteogenic differentiation.

The design of multifunctional localized drug delivery systems (LDDSs) has been endeavored in the past decades worldwide. The matrix material of LDDSs is known as a crucial factor for the success of its transformation from the laboratory to clinical practices. Herein, a biocompatible ceramic, strontium titanate (SrTiO3, STO), was utilized as the matrix. A variety of fine Er doped SrTiO3 (STO:Er) nanofibers were fabricated via electrospinning. After the surface functionalization with amino groups, the drug loading capacity of STO:Er nanofibers is dramatically increased. The nanofibers present a rather sustained drug releasing behavior in the media with pH of 7.4, and the release kinetics is significantly accelerated with the decreased pH value from 7.4 to 4.7. Furthermore, the intensity of the spectrum emitted from the STO:Er nanofibers corresponds well with the drug releasing progress under the excitation of near-infrared spectrum (∼980 nm). Fast drug release behavior (in an acid environment) induces a rapid intensity enhancing effect of photoluminescence emission and vice versa. The main mechanism is attributed to the quenching effect induced by the C-Hx groups of IBU molecules with vibration frequencies from 2850 to 3000 cm(-1). Such new STO:Er nanofibers with pH-triggered and optically monitored drug delivery functionalities have therefore been considered as another new localized drug delivery platform for modern tumor diagnosis and therapy.

Anatase TiO2 nanodot films have been found to be able to release cells under light illumination with excellent efficiency and safety. In the present study, we investigated the effects of rutile contents in TiO2 nanodot films on such light induced cell detachment behavior. The results showed that TiO2 nanodot films with different contents of rutile phase have been prepared successfully. The content of rutile phase increased with the increase in calcination temperature. All films possessed good cell adhesion but there was a decrease in cell proliferation with the increasing content of rutile phase. Single cell detachment assay showed that the films with high rutile contents (calcined at 900 °C and 1100 °C) showed better cell detachment performance. That was ascribed to the changes of the secondary structure of extracellular proteins adsorbed on the nanodot surface after ultraviolet (365 nm, UV365) illumination. In addition, cell sheets detached through UV365 illumination maintained high activity and could be further used in tissue engineering. The present work showed that the existence of rutile phase is helpful in cell detachment behavior and it could be utilized to optimize light-induced cell detachment behavior. Statement of Significance This work discovers that the presence of rutile phase in TiO2 nanodot films could improve the light-induced cell detachment behavior, although rutile phase is inferior to anatase phase on light induced superhydrophilicity. That strongly supported that the behaviors of adsorbed proteins are crucial in acquiring cell sheet with light illumination. In fact, the state and behavior of adsorbed protein greatly affect the interaction between biomaterials and living cells. Therefore, we consider this work is not only important in harvesting cells or cell sheets through light illumination, but also helpful in further understanding of interaction between biomaterials and cells.

For orthopedic implant coatings, excellent biological performance and anti-infective property have been both increasingly required for implantation surgery. In this work, TiO 2 nanorod films with good cellular responses and mesoporous bioactive glass (MBG) with good drug loading and release ability were adopted, and MBG-incorporated TiO 2 nanorod films were prepared by the sol–gel technique. The effects of TiO 2 nanorod density and MBG composition on the formation of the incorporated films were investigated. The results show that T-MBG (SiO 2 /CaO/P 2 O 5 /TiO 2 = 80/5/5/10) tightly cohered to TiO 2 nanorods in the films, and the degree of T-MBG incorporation ranged from about 100 nm to 300 nm of exposed TiO 2 nanorods in height. T-MBG incorporation had a positive role in the cytocompatibility of the films. Importantly, T-MBG incorporation improved greatly the drug release behavior of the TiO 2 nanorod films. The present work provides an approach to build organized nanostructure films on implant surfaces with satisfactory biological performance and essential anti-infective ability.

Europium (Eu) doped TiO 2 nanodot films were prepared through a phase-separation-induced self-assembly method. Eu was doped to impart the nanodots with luminescence property so that the protein adsorption could be in situ characterized quantitatively. Bovine serum albumin (BSA) was adsorbed on the surface of Eu-doped titanium nanodot films. It was found that the photo luminescence intensity at 616 nm decreased with the increase of BSA adsorption time. Also, Eu-doped TiO 2 nanodot films showed good biocompatibility. These results suggested that Eu-doped TiO 2 nanodot films could provide a feasible in situ way to evaluate protein adsorption if prepared on the surface of bioimplants.

Light-induced cell detachment on the substrate of TiO 2 nanodots has been proved to be a safe and attractive method for cell harvesting in tissue engineering. In order to improve the cell release efficiency, bioinert platinum with excellent charge transport loading in biocompatible graphite was prepared. 20 wt.% Pt/C powder showing excellent electrical, chemical and bioactive properties was incorporated to a TiO 2 system. We investigated the biocompatibility of Pt/C–TiO 2 composite films with different amounts of Pt/C with C/tetrabutyl titanate molar ratio varying from 0 to 0.42. The adhesion and proliferation rates of pre-osteoblastic MC3T3-E1 cells (mouse calvaria-derived) on the films prepared with the highest C/TiO 2 molar ratio are higher than that of the pure TiO 2 and other films, indicating a Pt/C dose-dependent effect. It is shown that the detachment efficiency of MC3T3-E1 cells depends on Pt/C amount and UV illumination time. Moreover, films prepared with C/tetrabutyl titanate molar ratio of 0.42 showed 93% cell detachment ratio within 5 min of UV illumination, while bare TiO 2 films only reached 75%, indicating an improved cell release efficiency by the incorporation of Pt/C. However, an interesting phenomenon was found that longer illumination time showed lower detachment ratios to some extent, which is contrary to our previous work. It is believed that this work presents the improved cell detachment efficiency by the incorporation of Pt/C.

In the present study, the effects of nanostructure on the light-induced cell detachment property of anatase TiO2 films are investigated and discussed. Anatase dense films, nanodots films and porous films are prepared through sol–gel and phase separation-induced self-assembly based methods. It is found that all the films possessed good cell adhesion but there is a decrease in cell proliferation in the dense film. The porous film exhibits improved cell detachment performance in both single cell and cell sheet detachment tests. It only takes about 3 min of ultraviolet illumination for cell sheets to detach from the porous film, while those for nanodots film and dense film are 5 min and 10 min, respectively. The cell sheets harvested show good performance and thus can be further utilized in cell sheet tissue engineering. The beneficial effects of film nanostructure are ascribed to the differences of initial adsorption status of extracellular proteins, as well as their changes after ultraviolet illumination. The present work demonstrates that optimization of film nanostructures could be an effective approach to improve light induced cell sheet harvesting.

Controlling protein adsorption on material surfaces can offer significant opportunities in terms of engineering the material–cell interactions. In this work, SrTiO3 cubic nanocrystals exposed with {100} facets, which was proved to have strong protein affinity previously, were used to assemble nano-microstructured surface. We demonstrated that the nano-microstructured surface with highly stacking density of the nanocrystals had enhanced cellular responses in cellular adhesion and proliferation compared to that of the (100)-terminated SrTiO3 single crystal substrate. The enhancement is attributed to more interaction sites resulting from heavy protein adsorption on {100} facets of the SrTiO3 cubic nanocrystals, and more appropriate cell growth microenvironment arising from the nanocrystals stacked nano-microstructure. The two factors are suggested to play critical role in material–cell interactions. The SrTiO3 cubic nanocrystals are powerful units to assemble surface nano/microstructure with highly biological responses.

750–850 nm (NIR I) and 1000–1400 nm (NIR II) in the near infrared (NIR) spectra are two windows of optical transparency for biological tissues with the latter capable of penetrating tissue deeper. Monitoring drug release from the drug carrier is still a daunting challenge in the field of nanomedicine. To overcome such a challenge, we propose to use porous Nd3+-doped CaTiO3 nanofibers, which can be excited by NIR I to emit NIR II light, to carry drugs to test the concept of monitoring drug release from the nanofibers by detecting the NIR II emission intensity. Towards this end, we first used electrospinning to prepare porous Nd3+-doped CaTiO3 nanofibers by adding micelle-forming surfactant Pluronic F127, followed by annealing to remove the organic component. After a model drug, ibuprofen, was loaded into the porous nanofibers, the drug release from the nanofibers into the phosphate buffered saline (PBS) solution was monitored by detecting the NIR II emission from the nanofibers. We found that the release of the drug molecules from the nanofibers into the PBS solution triggers the quenching of NIR II emission by the hydroxyl groups in the surrounding media. Consequently, more drug release corresponded to more reduction in the intensity of the NIR II emission, allowing us to monitor the drug release by simply detecting the intensity of NIR II from the nanofibers. In addition, we demonstrated that tuning the amount of micelle-forming surfactant Pluronic F127 enabled us to tune the porosity of the nanofibers and thus the drug release kinetics. This study suggests that Nd3+ doped CaTiO3 nanostructures can serve as a promising drug delivery platform with the potential to monitor drug release kinetics by detecting the tissue-penetrating NIR emission.

Carbon nanospheres were synthesized using a reduction–pyrolysis–catalysis process with the reaction of carbon tetrachloride and aluminum at low temperature (160 °C), which is much lower than that of traditional methods. The carbon nanospheres as an electrode for Li-ion batteries exhibited a high specific capacity of 719 mA h g−1 at a rate of 0.2 A g−1 (98.5% charge capacity retention) after 100 charge–discharge cycles.

BaTiO 3 /Ni 0.5 Zn 0.47 Fe 2 O 4 ceramic composites with various compositions were sintered at different temperatures. It is found both the formation and electromagnetic properties of the composite ceramics are strongly dependent on the percolation transition of NZFO. As NZFO content x is low ( x =0.1 and 0.2), the density increases with increasing the sintering temperature T from 1220 °C to 1300 °C, while it decreases as x is high ( x =0.65, 0.75 and 0.85). It is ascribed to the mismatch between the densification of BTO and NZFO. Both the permeability and low-frequency permittivity of the composites exhibit typical percolation behaviors, which are appropriate to the Kirkpatrick׳s effective medium model with the percolation threshold f c ranging from 0.35 to 0.5. As x f c , the permeability varies little and the low-frequency permittivity decreases with increasing T , owing to the dominant control of nonmagnetic BTO and the decrease in the defects in BTO, respectively. In comparison, as x > f c , both the permeability and permittivity increase considerably with increasing T . By analyzing the magnetic and dielectric dispersion spectra, it is revealed they are attributed respectively to the enhancement of domain-wall motion and the increase in the grain conductivity of NZFO.

Collagen/calcium phosphate nanocomposite coating similar to the natural bone structure is a promising material in surface modification of metallic implants to accelerate the osseointegration. In this chapter, electrochemical deposition was utilized to prepare collagen/calcium phosphate coating on titanium substrates successfully. A modified method called alternating potential-assisted electrochemical deposition (AP-ECD) was further proposed to modulate coating microstructures, making it possible to effectively achieve a controlled preparation of the collagen/calcium phosphate coating for different purposes. In vitro tests demonstrated that the desired cytocompatibility, loading/release behavior, and antibacterial property of the coatings were realized, intensifying its biological role as differentiation inducer and promoting the osteogenic differentiation. In vivo tests further confirmed that the implant with the collagen/calcium phosphate coatings showed higher new bone density and pull out strength, and the significantly accelerated osseointegration was realized. The AP-ECD method could provide a basis for function design and controlled preparation of collagen/calcium phosphate composite coatings, favoring for different biological applications.

Effective regulation of cell-surface interactions is critical for regenerative medicine and other cell-based therapies. Herein, visible-light-induced cell sheet harvesting based on silicon wafers with a p/n junction [Si(p/n)] is introduced. Cell sheets could quickly detach from the Si(p/n) surface after 10 min of visible-light illumination with maintained cell viability and functions. It is found that preadsorbed proteins on the Si(p/n) surface like BSA and collagen-I show light-induced desorption behaviors. Molecular dynamics simulation also indicates that long-range force caused by the photovoltaic effect of Si(p/n) under visible-light illumination plays a key role in triggering the release of the preadsorbed protein. It is suggested that such protein desorption behavior mediated by the photovoltaic effect is responsible for cell release. This work not only shows promising potential for cell sheet harvesting, but also provides new insights into protein-material interactions.

Two important goals in orthopedic implant research are to promote osseointegration and prevent infection. However, much previous effort has been focused on the design of coatings to either enhance osseointegration while ignoring antibacterial activity or vice versa, to prevent infection while ignoring bone integration. Here, we designed a multifunctional mineralized collagen coating on titanium with the aid of metal-organic framework (MOF) nanocrystals to control the release of naringin, a Chinese herbal medicine that could promote osseointegration and prevent bacterial infection. The attachment, proliferation, osteogenic differentiation, and mineralization of mesenchymal stem cells on the coating were significantly enhanced. Meanwhile, the antibacterial abilities against Staphylococcus aureus were also promoted. Furthermore, release kinetics analysis indicated that the synergistic effect of a primary burst release stage and secondary slow release stage played a critical role in the performance and could be controlled by the relative concentrations of MOF and naringin. This work thus provides a novel strategy to engineer multifunctional orthopedic coatings that can enhance osseointegration and simultaneously inhibit microbial cell growth.

A series of SrTiO3 polyhedral submicro/nanocrystals with systematic morphology evolution from cubic to edge-truncated cubic and truncated rhombic dodecahedra have been synthesized by using a series of alcohol molecules with different acidities as surfactants. The concentration and pK a value of the alcohols both play important roles in determining the size and shape of the SrTiO3 polyhedral submicro/nanocrystals. The adsorption energy of alcohol molecules on SrTiO3 {110} facets depends on their pK a values, which are therefore critical for morphology control. Using the same strategy, a series of BaTiO3 polyhedral submicro/nanocrystals with systematic morphology evolution have also been successfully prepared.

Controlling the formation of conductive particles to be nano-scale is important for achieving percolation effect in metal dispersed thin film composite to contribute extraordinary dielectric properties required for miniaturization of electronic devices. In this paper, lactic acid (LA) and citric acid (CA) were used as dual complexing agents to prepare a typical Ag nanoparticle dispersed PbTiO 3 (PTO) composite thin film by using a sol-gel method. The phase structure of the thin film and the coordination effect between complexing agent and metallic ions were investigated. It revealed that LA coordinated with Ti 4 + and Pb 2 + and CA coordinated with Ag + . Lead was fixed inside the gel network by LA and restricted to evaporate during heat treatment thus the pyrochlore phase was prevented from forming in the thin film. Ag + was coordinated by CA and the diffusion and thus aggregation of silver during gelation and annealing process were weakened. Silver nanoparticles dispersed in the PTO matrix formed with dual complexing agents of LA and CA introduced during the preparation process. The composite thin film of perfect perovskite phase with silver nanoparticles embedded was obtained at the molar ratio of LA/lead = 0.5 and CA/lead = 0.5. The dielectric constant of the thin film with silver nanoparticles is 5 times higher than that without silver nanoparticles.