Biomimetic Elastomeric Bioactive Siloxane‐Based Hybrid Nanofibrous Scaffolds with miRNA Activation: A Joint Physico‐Chemical‐Biological Strategy for Promoting Bone Regeneration

Rapid and efficient disease‐induced or critical‐size bone regeneration remains a challenge in tissue engineering due to the lack of highly bioactive biomaterial scaffolds. Physical structures such as nanostructures, chemical components such as silicon elements, and biological factors such as genes have shown positive effects on bone regeneration. Herein, a bioactive photoluminescent elastomeric silicate‐based nanofibrous scaffold with sustained miRNA release is reported for promoting bone regeneration based on a joint physico‐chemical‐biological strategy. Bioactive nanofibrous scaffolds are fabricated by cospinning poly (ε‐caprolactone) (PCL), elastomeric poly (citrates‐siloxane) (PCS), and bioactive osteogenic miRNA nanocomplexes (denoted PPM nanofibrous scaffolds). The PPM scaffolds possess uniform nanostructures, significantly enhanced tensile stress (≈15 MPa) and modulus (≈32 MPa), improved hydrophilicity (30–60°), controlled biodegradation, and strong blue fluorescence. Bioactive miRNA complexes are efficiently loaded into the nanofibrous matrix and exhibit long‐term release for up to 70 h. The PPM scaffolds significantly promote the adhesion, proliferation, and osteoblast differentiation of bone marrow stem cells in vitro and enhanced rat cranial defect restoration (12 weeks) in vivo. This work reports an attractive joint physico‐chemical‐biological strategy for the design of novel cell/protein‐free bioactive scaffolds for synergistic tissue regeneration.     

Porous Polymersomes with Encapsulated Gd‐Labeled Dendrimers as Highly Efficient MRI Contrast Agents

The use of nanovesicles with encapsulated Gd as magnetic resonance (MR) contrast agents has largely been ignored due to the detrimental effects of the slow water exchange rate through the vesicle bilayer on the relaxivity of encapsulated Gd. Here, the facile synthesis of a composite MR contrast platform is described; it consists of dendrimer conjugates encapsulated in porous polymersomes. These nanoparticles exhibit improved permeability to water flux and a large capacity to store chelated Gd within the aqueous lumen, resulting in enhanced longitudinal relaxivity. The porous polymersomes, ～130 nm in diameter, are produced through the aqueous assembly of the polymers, polyethylene oxide‐b‐polybutadiene (PBdEO), and polyethylene oxide‐b‐polycaprolactone (PEOCL). Subsequent hydrolysis of the caprolactone (CL) block resulted in a highly permeable outer membrane. To prevent the leakage of small Gd‐chelate through the pores, Gd was conjugated to polyamidoamine (PAMAM) dendrimers via diethylenetriaminepentaacetic acid dianhydride (DTPA dianhydride) prior to encapsulation. As a result of the slower rotational correlation time of Gd‐labeled dendrimers, the porous outer membrane of the nanovesicle, and the high Gd payload, these functional nanoparticles are found to exhibit a relaxivity (R1) of 292 109 mM ^?1 s^?1 per particle. The polymersomes are also found to exhibit unique pharmacokinetics with a circulation half‐life of >3.5 h and predominantly renal clearance.     

Targeted Tumor Hypoxia Dual‐Mode CT/MR Imaging and Enhanced Radiation Therapy Using Dendrimer‐Based Nanosensitizers

The efficacy of radiation therapy (RT) is often limited by the poor response of hypoxia inside most solid tumors. The development of a theranostic nanoplatform for precision‐imaging‐guided sensitized RT for tumor hypoxia is still challenging. Herein, the creation of hypoxia‐targeted dendrimer‐entrapped gold nanoparticles complexed with gadolinium(III) (Gd‐Au DENPs‐Nit) for dual‐mode CT/MR imaging and sensitized RT of hypoxic tumors is reported. In this work, generation 5 poly(amidoamine) dendrimers are partially conjugated with Gd(III) chelator, entrapped with Au nanoparticles, and conjugated with hypoxia‐targeting agent nitroimidazole via a polyethylene glycol linker, and ending with chelation of Gd(III) and conversion of their leftover amine termini to acetamides. The designed dendrimer‐based nanohybrids with 3.2 nm Au cores exhibit an excellent X‐ray attenuation effect, acceptable r₁ relaxivity (1.32 mM^?1 s^?1), and enhanced cellular uptake in hypoxic cancer cells, affording efficient dual‐mode CT/MR imaging of tumor hypoxia. Under X‐ray irradiation, the Gd‐Au DENPs‐Nit nanohybrids can produce reactive oxygen species, promote DNA damage, and prevent DNA repair, facilitating sensitized RT of hypoxic cancer cells in vitro and tumor hypoxia in vivo. The developed hypoxia‐targeted dendrimer‐based nanohybrids may be employed as both contrast agents and nanosensitizers for precision tumor hypoxia imaging and sensitized tumor RT.     

Piezoelectric Nanotopography Induced Neuron‐Like Differentiation of Stem Cells

The biophysical characteristics of the extracellular matrix, such as nanotopography and bioelectricity, have a profound influence on cell proliferation, adhesion, differentiation, etc. Recognition of the function of a certain biophysical cue and fabrication of biomaterial scaffolds with specific properties would have important implications and significant applications in tissue engineering. Herein, nanotopographic and piezoelectric biomaterials are fabricated and the combination effect of and individual contribution to proliferation, adhesion, and neuron‐like differentiation of rat bone marrow‐derived mesenchymal stem cells (rbMSCs) are clarified via nanotopography and piezoelectricity. Piezoelectric polyvinylidene fluoride with nanostripe array structures is fabricated, which can generate a surface piezoelectric potential up to millivolt by cell movement and traction. The results reveal a more favorable effect on neuron‐like differentiation of rbMSCs from the combination of piezoelectricity and nanotopography rather than nanotopography alone, whereas nanotopography can increase cellular adhesion. This research provides a new insight into designing biomaterials for the potential application in neural tissue engineering.     

Facile Stem Cell Delivery to Bone Grafts Enabled by Smart Shape Recovery and Stiffening of Degradable Synthetic Periosteal Membranes

Delivering stem/progenitor cells via a degradable synthetic membrane to devitalized allogenic tissue graft surfaces presents a promising allograft‐mediated tissue regeneration strategy. However, balancing degradability and bioactivity of the synthetic membrane with physical characteristics demanded for successful clinical translation is challenging. Here, well‐integrated composites of hydroxyapatite (HA) and amphiphilic poly(lactide‐co‐glycolide)‐b‐poly(ethylene glycol)‐b‐poly(lactide‐co‐glycolide) (PELGA) with tunable degradation rates are designed that stiffen upon hydration and exhibit excellent shape recovery ability at body temperature for efficiently delivering skeletal progenitor cells around bone grafts. Unlike conventional degradable polymers that weaken upon wetting, these amphiphilic composites stiffen upon hydration as a result of enhanced polyethylene glycol (PEG) crystallization. HA‐PELGA composite membranes support the attachment, proliferation, and osteogenesis of rat periosteum‐derived cells in vitro, as well as the facile transfer of confluent cell sheets of green fluorescent protein‐labeled bone marrow stromal cells. With efficient shape memory behaviors around physiological temperature, the composite membranes can be programmed with a permanent tubular configuration, deformed into a flat temporary shape desired for cell seeding/cell sheet transfer, and triggered to wrap around a femoral bone allograft upon 37 °C saline rinse and subsequently stiffen. These properties combined make electrospun HA‐PELGA promising smart synthetic periosteal membranes for augmenting allograft healing.     

A Fluorinated Bola‐Amphiphilic Dendrimer for On‐Demand Delivery of siRNA,via Specific Response to Reactive Oxygen Species

Functional materials capable of responding to stimuli intrinsic to diseases are extremely important for specific drug delivery at the disease site. However, developing on‐demand stimulus‐responsive vectors for targeted delivery is highly challenging. Here, a stimulus‐responsive fluorinated bola‐amphiphilic dendrimer is reported for on‐demand delivery of small interfering RNA (siRNA) in response to the characteristic high level of reactive oxygen species (ROS) in cancer cells. This dendrimer bears a ROS‐sensitive thioacetal in the hydrophobic core and positively charged poly(amidoamine) dendrons at the terminals, capable of interacting and compacting the negatively charged siRNA into nanoparticles to protect the siRNA and promote cellular uptake. The ROS‐sensitive feature of this dendrimer boosts specific and efficient disassembly of the siRNA/vector complexes in ROS‐rich cancer cells for effective siRNA delivery and gene silencing. Moreover, the fluorine tags in the vector enable ¹⁹F‐NMR analysis of the ROS‐responsive delivery process. In addition, this ingenious and distinct bola‐amphiphilic dendrimer is also able to combine the advantageous delivery features of both lipid and dendrimer vectors. Therefore, it represents an innovative on‐demand stimulus‐responsive delivery platform.     

Multifunctional Dendrimer‐Templated Antibody Presentation on Biosensor Surfaces for Improved Biomarker Detection

Dendrimers, with their well‐defined globular shape and high density of functional groups, are ideal nanoscale materials for templating sensor surfaces. This work exploits dendrimers as a versatile platform for capturing biomarkers with improved sensitivity and specificity. The synthesis, characterization, fabrication, and functional validation of the dendrimer‐based assay platform are described. Bifunctional hydroxyl/thiol‐functionalized G4‐polyamidoamine (PAMAM) dendrimer is synthesized and immobilized on the polyethylene‐glycol (PEG)‐functionalized assay plate by coupling PEG‐maleimide and dendrimer thiol groups. Simultaneously, part of the dendrimer thiol groups are converted to hydrazide functionalities. The resulting dendrimer‐modified surface is coupled to the capture antibody in the Fc region of the oxidized antibody. This preserves the orientation flexibility of the antigen binding region (Fv) of the antibody. To validate the approach, the fabricated plates are further used as a solid phase for developing a sandwich‐type enzyme‐linked immunosorbent assay (ELISA) to detect IL‐6 and IL‐1β, important biomarkers for early stages of chorioamnionitis. The dendrimer‐modified plate provides assays with significantly enhanced sensitivity, lower nonspecific adsorption, and a detection limit of 0.13 pg mL^?1 for IL‐6 luminol detection and 1.15 pg mL^?1 for IL‐1β TMB detection, which are significantly better than those for the traditional ELISA. The assays were validated in human serum samples from a normal (nonpregnant) woman and pregnant women with pyelonephritis. The specificity and the improved sensitivity of the dendrimer‐based capture strategy could have significant implications for the detection of a wide range of cytokines and biomarkers since the capture strategy could be applied to multiplex microbead assays, conductometric immunosensors, and field‐effect biosensors.     

Dendrimer‐Based,High‐Luminescence Conjugated Microporous Polymer Films for Highly Sensitive and Selective Volatile Organic Compound Sensor Arrays

Conjugated microporous polymers (CMPs) are attracting increasing attention in chemical sensing due to their extended π‐conjugated framework, permanent microporous structure, and large specific surface area. However, the extremely poor solubility and processability of CMPs, as well as the serious fluorescence quenching caused by aggregation, restrict their practical applications. Herein, a high‐luminescence CMP film is constructed based on a novel dendrimer (TPETCz) featured by its central tetraphenylethylene “core” with aggregation‐induced emission effect and its highly electro‐active “branches.” High specific surface area CMP films for analyte diffusion are fabricated by a facile in situ electropolymerization method. These dendrimer‐based CMP films exhibit superior sensitivity to volatile organic compounds (VOCs). More importantly, 18 types, the most types reported, of VOC vapors are precisely distinguished by the linear discriminant analysis by establishing a 2D fluorescence sensor array based on the CMP films and the dendrimer monomer films.     

A Dendrimer‐Based Electropolymerized Microporous Film: Multifunctional,Reversible, and Highly Sensitive Fluorescent Probe

A dendrimer PYTPAG2 composed of a central pyrene “core” and four exterior “arms” capped with electroactive triphenylamine is developed as an electroactive precursor to prepare fluorescent films through electropolymerization (EP). The fluorescence emission comes from the central pyrene “core” and the steric hindrance of the exterior “arms” is beneficial for the formation of microporous morphology. The stable and highly cross‐linked fluorescent EP films can be obtained even as free‐standing films. Further, these dendrimer EP films are first studied as the multifunctional fluorescent probe: the emission of EP films exposed to trinitrotoluene vapor is quenched by 82% in 120 s; while the fluorescence is increased to nearly 400% in 120 s upon exposure to benzene vapor, EP films also act as the fluorescent sensor to Fe³⁺ in solution and the limit of detection is obtained to be 8.5 × 10^?8 m . All the above detection processes exhibit remarkable reversibility. These excellent performances are attributed to both the specific molecular features of PYTPAG2 and the intrinsic properties of EP films.     

Intracellular Microenvironment‐Responsive Dendrimer‐Like Mesoporous Nanohybrids for Traceable,Effective, and Safe Gene Delivery

In order to create advanced functional nanocarriers for efficient gene therapy, novel intracellular microenvironment‐sensitive fluorescence label‐free nanostructured dendrimer‐like silica hybrid nanocarriers are developed for traceable, effective, and safe gene delivery. Dendrimer‐like mesoporous silica nanoparticles (DMSNs) with center‐radial large pores are covalently modified with short polyethyleneimine (PEI) for efficient gene loading and binding. Autofluorescent and biodegradable PEI (AC‐PEI) responsive to the intracellular microenvironment are then coated on the gene‐loaded nanoparticles for inhibiting gene leakage from the carriers. Moreover, AC‐PEI coating not only endows intracellular microenvironment‐responsive gene release property, but also allows monitoring the gene delivery process in the absence of external labelling, owing to the pH‐ and GSH‐responsive autofluorescence and biodegradability of AC‐PEI. The resultant nanocarriers show high gene loading capacity, low cytotoxicity, stimuli‐responsive gene release, label‐free, and simultaneous fluorescence tracking, and high gene silencing capability. Thus, these developed nanocarriers hold substantial and promising potential as effective and safe gene‐delivery carriers for future scientific investigation and practical implications in gene therapy.     

Tetrahydro[5]helicene‐Based Nanoparticles for Structure‐Dependent Cell Fluorescent Imaging

Four new fluorescent dyes containing tetrahydro[5]helicene moiety characterized by three‐primary emission colors (blue‐green‐red) are designed and synthesized, and their structures are characterized by NMR, MS, and single crystal X‐ray crystallography. Organic nanoparticles based on the fluorescent dyes are then prepared by re‐precipitation method, and their photophysical properties are investigated. These nanoparticles retain the strong emissions of the organic dyes, and multicolor nanoparticles were also prepared by simply tuning the ratios of the three‐primary colors dyes. These organic nanoparticles exhibit low cytotoxicity, good photostability, and high quantum yields. Moreover, the nanoparticles can also be applied in the cell fluorescence imaging. Especially, it is interestingly found that the stained regions of these nanoparticles from membrane to cytoplasm for HeLa cells show obvious structure‐dependent properties. This strategy provides a new perspective to fluorescence probe by molecular design for specific location imaging of living cells.     

Polydopamine Encapsulation of Fluorescent Nanodiamonds for Biomedical Applications

Fluorescent nanodiamonds (FNDs) are promising bioimaging probes compared with other fluorescent nanomaterials such as quantum dots, dye‐doped nanoparticles, and metallic nanoclusters, due to their remarkable optical properties and excellent biocompatibility. Nevertheless, they are prone to aggregation in physiological salt solutions, and modifying their surface to conjugate biologically active agents remains challenging. Here, inspired by the adhesive protein of marine mussels, encapsulation of FNDs within a polydopamine (PDA) shell is demonstrated. These PDA surfaces are readily modified via Michael addition or Schiff base reactions with molecules presenting thiol or nitrogen derivatives. Modification of PDA shells by thiol terminated poly(ethylene glycol) (PEG‐SH) molecules to enhance colloidal stability and biocompatibility of FNDs is described. Their use as fluorescent probes for cell imaging is demonstrated; it is found that PEGylated FNDs are taken up by HeLa cells and mouse bone marrow‐derived dendritic cells and exhibit reduced nonspecific membrane adhesion. Furthermore, functionalization with biotin‐PEG‐SH is demonstrated and long‐term high‐resolution single‐molecule fluorescence based tracking measurements of FNDs tethered via streptavidin to individual biotinylated DNA molecules are performed. This robust polydopamine encapsulation and functionalization strategy presents a facile route to develop FNDs as multifunctional labels, drug delivery vehicles, and targeting agents for biomedical applications.     

Preparation of Near‐IR Fluorescent Nanoparticles for Fluorescence‐Anisotropy‐Based Immunoagglutination Assay in Whole Blood

A class of novel core/shell near‐IR fluorescent nanoparticles have been prepared through co‐hydrolysis of a hydrophobic silicon alkoxide, hexadecyltrimethoxysilane, and tetraethyl orthosilicate as the dye‐doped core, followed by the formation of a hydrophilic shell via hydrolysis of tetraethyl orthosilicate in a water‐in‐oil microemulsion. The co‐hydrolysis of hexadecyltrimethoxysilane and tetraethyl orthosilicate produces a highly hydrophobic core for the entrapment of a low‐cost near‐IR fluorescence dye, methylene blue. Experimental investigation of this particular core/shell nanoparticle in comparison with conventional dye‐doped silica nanoparticles demonstrates that the hydrophobic core enables the doped dye to exhibit enhanced fluorescence and show improved stability to dye leaching and exogenous quenchers. In contrast to rhodamine B doped silica nanoparticles, the near‐IR fluorescent nanoparticles also show negligible background fluorescence and low inner‐filtration interference in complex biological systems such as whole blood. This advantage is utilized for the development of an immunoagglutination assay method based on fluorescence‐anisotropy measurement for the detection of alpha fetoprotein (AFP) in whole‐blood samples. The results reveal that increase in fluorescence anisotropy is linearly correlated with AFP concentration in the range 1.9–51.9 ng mL^–1.     

Thermodynamically Controlled Self‐Assembly of Hierarchically Staggered Architecture as an Osteoinductive Alternative to Bone Autografts

Osteoinductive synthetic biomaterials for replacing autografts can be developed by mimicking bone hierarchy and surface topography for host cell recruitment and differentiation. Until now, it has been challenging to reproduce a bone‐like staggered hierarchical structure since the energy change underlying synthetic pathways in vitro is essentially different from that of the natural process in vivo. Herein, a bone‐like hierarchically staggered architecture is reproduced under thermodynamic control involving two steps: fabrication of a high‐energy polyacrylic acid‐calcium intermediate and selective mineralization in collagenous gap regions driven by an energetically downhill process. The intermediate energy interval could easily be adjusted to determine different mineralization modes, with distinct morphologies and biofunctions. Similar to bone autografts, the staggered architecture offers a bone‐specific microenvironment for stem cell recruitment and multidifferentiation in vitro, and induces neo‐bone formation with bone marrow blood vessels by host stem cell homing in vivo. This work provides a novel perspective for an in vitro simulating biological mineralization process and proof of concept for the clinical application of smart biomaterials.     

Ultrasensitive,Biocompatible, Quantum‐Dot‐Embedded Silica Nanoparticles for Bioimaging

The successful development of highly sensitive, water‐compatible, nontoxic nanoprobes has allowed nanomaterials to be widely employed in various applications. The applicability of highly bright quantum dot (QD)‐based probes consisting of QDs on 120 nm silica nanoparticles (NPs) with silica shells is investigated. Their substantial merits, such as their brightness and biocompatibility, for effective bioimaging are demonstrated. Silica‐coated, QD‐embedded silica NPs (Si@QDs@Si NPs) containing QDs composed of CdSe@ZnS (core‐shell) are prepared to compare their structure‐based advantages over single QDs that have a similar quantum yield (QY). These Si@QDs@Si NPs exhibit approximately 200‐times stronger photoluminescence (PL) than single QDs. Cytotoxicity studies reveal that the Si@QDs@Si NPs are less toxic than equivalent numbers of silica‐free single quantum dots. The excellence of the Si@QDs@Si NPs with regard to in vivo applications is illustrated by significantly enhanced fluorescence signals from Si@QDs@Si‐NP‐tagged cells implanted in mice. Notably, a more advanced version of QD‐based silica NPs (Si@mQDs@Si NPs), containing multishell quantum dots (mQDs) composed of CdSe@CdS@ZnS, are prepared without significant loss of QY during surface modification. In addition, the Si@mQDs@Si NPs display a fivefold higher fluorescence activity than the Si@QDs@Si NPs. As few as 400 units of Si@mQDs@Si‐ NP‐internalized cells can be detected in the cell‐implanted mouse model.     

Coupling BCP Ceramics with Micro-Vibration Stimulation Field for Cascade Amplification from Immune Activation to Bone Regeneration

The osteoimmunology has revealed that immune system plays an important role in maintaining bone metabolism and remodeling. As long-term physiological factor in bone, mechanical stimulation such as micro-vibration stimulation (MVS) exerts effects on regulating osteogenesis and immune response. In this study, the osteo-immunodulatory effects of bicalcium phosphate (BCP) ceramics coupled with MVS are investigated. This results find that the combination of BCP ceramics and MVS may exert synergistic effects on the polarization and functional status of macrophages through activating plasma membrance Ca²⁺ ATPase (PMCA) channel, reducing the intracellular calcium ion concentration, and inhibiting downstream extracellular signal-regulated kinase (ERK)1/2 signaling pathway. BCP ceramics coupled MVS could drive the macrophage polarization to wound-healing M2 phenotype to decrease the production of pro-inflammatory factors, enhance the secretion of anti-inflammatory cytokines and growth factors such as transforming growth factor (TGF)-β1 and bone morphogenetic protein (BMP)-2. Moreover, BCP and MVS-modulated macrophage secretion pattern can trigger the BMP/TGF-Smad signaling pathways to induce osteoblastic differentiation of bone marrow mesenchymal stromal cells (BM-MSCs) in vitro, and maintain cellular viability and promote the formation of collagen-rich osteoid like tissues and mature blood vessels in vivo. This study demonstrates that the introduction of mechanical stimuli like non-invasive MVS is an effective strategy to improve bone repair effects of biomaterials through endowing them with superior osteo-immunodulatory capacity.     

Light‐Triggered Clustered Vesicles with Self‐Supplied Oxygen and Tissue Penetrability for Photodynamic Therapy against Hypoxic Tumor

Smart nanocarriers are of particular interest for highly effective photodynamic therapy (PDT) in the field of precision nanomedicine. Nevertheless, a critical challenge still remains in the exploration of potent PDT treatment against hypoxic tumor. Herein, light‐triggered clustered polymeric vesicles for photoinduced hypoxic tumor ablation are demonstrated, which are able to deeply penetrate into the tumor and simultaneously afford oxygen supply upon light irradiation. Hydrogen peroxide (H₂O₂) and poly(amidoamine) dendrimer conjugating chlorin e6/cypate (CC‐PAMAM) are coassembled with reactive‐oxygen‐species‐responsive triblock copolymer into the polymeric vesicles. Upon 805 nm irradiation, the vesicles exhibit the light‐triggered thermal effect that is able to decompose H₂O₂ into O₂, which distinctly ensures the alleviation of tumor hypoxia at tumor. Followed by 660 nm irradiation, the vesicles are rapidly destabilized through singlet oxygen‐mediated cleavage of copolymer under light irradiation and thus allow the release of photoactive CC‐PAMAM from the vesicular chambers, followed by their deep penetration in the poorly permeable tumor. Consequently, the light‐triggered vesicles with both self‐supplied oxygen and deep tissue penetrability achieve the total ablation of hypoxic hypopermeable pancreatic tumor through photodynamic damage. These findings represent a general and smart nanoplatform for effective photoinduced treatment against hypoxic tumor.     

Engineered 3D Silk‐Based Metastasis Models: Interactions Between Human Breast Adenocarcinoma,Mesenchymal Stem Cells and Osteoblast‐Like Cells

Bone metastasis occurs in 70% of breast cancer patients and is a frequent cause of morbidity in cancer patients. A delicate balance exists in the bone microenvironment, but the functional dynamics underlying the tumor cell‐microenvironment interactions remain poorly understood. 3D in vitro model systems of metastasis can throw new light on this phenomenon. Silk protein fibroin scaffolds, are cytocompatible for 3D cancer cell culture. They are structurally more resistant to protease degradation than other native biomaterials making these matrices suitable for cancer modeling. In this report, human breast adenocarcinoma cells, human osteoblast like cells and mesenchymal stem cells are co‐cultered. Cancer cells and osteoblast‐like cells are found to interact through secreted products. Decreased population of osteoblast‐like cells and mineralization of extracellular matrix are observed as a result of co‐culture. Significantly increased migration of breast cancer cells is observed in the bone‐like constructs than in non‐seeded scaffolds. The co‐culture constructs show significant increase in drug resistance, invasiveness and angiogenicity. Co‐culture of breast cancer cells with osteoblast like cells and mesenchymal stem cells also indicate that the interaction of cancer cells with bone microenvironment varies with spatial organization, presence of osteogenic factors as well as stromal cell type. Here, results show that 3D in vitro co‐culture models is possibly a better system to study and target cancer progression.     

Metal Ion/Dendrimer Complexes with Tunable Work Functions in a Wide Range and Their Application as Electron‐ and Hole‐Transport Materials of Non‐Fullerene Organic Solar Cells

The work functions of electrodes can be modified by adding charge transport layers to have good energy level matching with the active materials for organic solar cells (OSCs). Usually, a certain material gives rise to one definite work function of an electrode. In this work it is demonstrated that complexes of poly(amido amine) (generation 3) (PAMAM) with Cu²⁺ can continuously tune the work function of indium tin oxide (ITO) in a range of 4–5 eV by controlling the ratio of Cu²⁺ to PAMAM. PAMAM can lower the work function of ITO from 4.60 to 4.07 eV, while Cu²⁺‐PAMAM can increase the work function. The work function increase depends on the Cu²⁺‐to‐PAMAM molar ratio, and the work function can be up to 4.96 eV. The Cu²⁺ effect is ascribed the Cu²⁺‐caused change in the dipole moment of PAMAM. Moreover, this method can be used to continuously modify the work function of other materials, including Ag, Au, poly(3,4‐ethylenedioxythiophene):polystyrene sulfonate, and reduced graphene oxide. In addition, PAMAM and Cu²⁺‐PAMAM are investigated as the charge collection buffer materials of non‐fullerene OSCs of poly[(2,6‐(4,8‐bis(5‐(2‐ethylhexyl)thiophen‐2‐yl)‐benzo[1,2‐b:4,5‐b′]dithiophene))‐alt‐(5,5‐(1′,3′‐di‐2‐thienyl‐5′,7′‐bis(2‐ethylhexyl)benzo[1′,2′‐c:4′,5′‐c′]dithiophene‐4,8‐dione))]: 3,9‐bis(2‐methylene‐(3‐(1,1‐dicyanomethylene)‐indanone))‐5,5,11,11‐tetrakis(4‐hexylphenyl)‐dithieno[2,3‐d:2′,3′‐d′]‐s‐indaceno[1,2‐b:5,6‐b′]dithiophene). The power conversion efficiency can reach 9.2%, which is comparable to that using conventional charge transport materials.     

Polyphenylene Dendrimer‐Templated In Situ Construction of Inorganic–Organic Hybrid Rice‐Shaped Architectures

A novel dendrimer‐templating method for the synthesis of CuO nanoparticles and the in situ construction of ordered inorganic–organic CuO–G2Td(COOH)₁₆rice‐shaped architectures (RSAs) with analogous monocrystalline structures are reported. The primary CuO nanoparticles are linked by the G2Td(COOH)₁₆ dendrimer. This method provides a way to preserve the original properties of primary CuO nanoparticles in the ordered hybrid nanomaterials by using the 3D rigid polyphenylene dendrimer (G2Td(COOH)₁₆) as a space isolation. The primary CuO nanoparticles with diameter of (6.3 ± 0.4) nm are synthesized via four successive reaction steps starting from the rapid reduction of Cu(NO₃)₂ by using NaBH₄ as reducer and G2Td(COOH)₁₆ as surfactant. The obtained hybrid CuO–G2Td(COOH)₁₆ RSA, formed in the last reaction step, possesses a crystal structure analogous to a monocrystal as observed by transmission electron microscopy(TEM). In particular, the formation process of the RSA is monitored by UV–vis, TEM, and X‐ray diffraction. Small angle X‐ray scattering and Fourier transform infrared spectroscopy are used to investigate the role of the dendrimer in the RSA formation process. The obtained results illuminate that Cu²⁺? COO^? coordination bonds play an indispensable role in bridging and dispersing the primary CuO nanoparticles to induce and maintain the hybrid RSA. More importantly, the RSA is retained through the Cu²⁺? COO^?coordination bonds even with HCl treatment, suggesting that the dendrimers and Cu²⁺ ions may form rice‐shaped polymeric complexes which could template the assembly of CuO nanoparticles towards RSAs. This study highlights the feasibility and flexibility of employing the peculiar dendrimers to in‐situ build up hybrid architectures which could further serve as templates, containers or nanoreactors for the synthesis of other nanomaterials.