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In order to investigate the thermal decomposition kinetics and mechanism of nitrocellulose (NC) based nitramine explosives nanocomposite energetic materials, this work prepares NC/RDX (cyclotrimethylenetrinitramine), NC/HMX (cyclotetramethylenetetranitramine), and NC/CL‐20 (hexanitrohexaazaisowurtzitane) composites by a combined sol‐gel and the freeze‐drying technology. The structure is systematically investigated and the results reveal that the explosive particles are dispersed, filled, or embedded homogenously in the gel matrix of NC, thereby restricting the crystal growth of RDX, HMX, CL‐20 particles to coarse and achieving submicron/nanometer. The thermal analysis of composites exhibits much lower peak temperature compared with raw explosive crystal, furthermore, the activation energy (Ea) of composites is also lower than that of both NC and explosives. Hence, the unique structure of NC gel matrix embedded explosives inside demonstrated different mechanism of decomposition. Concretely, the rupture of the H‐NCO = O bond in the cross‐linked structure is detected firstly, subsequently, the macromolecular chains’ scission site of gel firstly occurs at ‐C‐O‐C‐ in the ring, and then the scission of ‐NO2 (from NC or explosive crystals) bonds happened. Hence, this study may provide promising fabrication strategy and basic theory for the application of NC‐based nanocomposite energetics in high‐energy propellants and explosives.

Astrocyte is the most abundant cells in brain and plays critical roles in brain homeostasis and functions. Although hyperthermia (or fever) is a common symptom in patients, its influence on astrocyte viability, morphology, and functions remains elusive. Here we developed an in vitro astrocyte culture system capable of precisely controlling culture temperature to study astrocyte responses under clinically-relevant hyperthermic temperatures (38 ∼ 41°C). We found that hyperthermia in this temperature range does not alter cell morphology, but significantly affects cell viability, activation and functions. Specifically, high-hyperthermia (40°C and 41°C) causes irreversible and permanent damages to astrocytes and compromises their normal viability and functionalities repairing damaged neural tissue, recycling neurotransmitters, and promoting brain development, while mild-hyperthermia (38°C and 39°C) induces astrocyte activation and cytokine secretion without significant decreases in cell viability. This study sheds new insights into our understanding of various fever-associated symptoms, enabling the future development of astrocyte-targeted therapy to treat brain diseases via hyperthermia.

Diabetic patients suffer from peripheral nerve injury with slow and incomplete regeneration owing to hyperglycemia and microvascular complications. This study develops a graphene-based nerve guidance conduit by incorporating natural double network hydrogel and a neurotrophic concentration gradient with non-invasive treatment for diabetics. GelMA/silk fibroin double network hydrogel plays quadruple roles for rapid setting/curing, suitable mechanical supporting, good biocompatibility, and sustainable growth factor delivery. Meanwhile, graphene mesh can improve the toughness of conduit and enhance conductivity of conduit for regeneration. Here, novel silk tapes show quick and tough adhesion of wet tissue by dual mechanism to replace suture step. The in vivo results demonstrate that gradient concentration of netrin-1 in conduit have better performance than uniform concentration caused by chemotaxis phenomenon for axon extension, remyelination, and angiogenesis. Altogether, GelMA/silk graphene conduit with gradient netrin-1 and dry double-sided adhesive tape can significantly promote repairing of peripheral nerve injury and inhibit the atrophy of muscles for diabetics.

DNA-templated silver nanoclusters (AgNCs) are an emerging class of ultrasmall (

Graphene materials have attracted special attention because of their electrical conductivity, mechanical properties, and favorable biocompatibility. Although various methods have been developed for fabricating micro/nano conductive fibrous scaffolds, it is still challenging to fabricate the three-dimensional (3D) graphene fibrous scaffolds. Herein, we developed a new method, termed as microfluidic 3D printing technology (M3DP), to fabricate 3D graphene oxide (GO) microfibrous scaffolds with an adjustable fiber length, fiber diameter, and scaffold structure by integrating the microfluidic spinning technology with a programmable 3D printing system. GO microfibrous scaffolds were then transformed into conductive reduced graphene oxide (rGO) microfibrous scaffolds by hydrothermal reduction. Our results demonstrated that the fabricated 3D fibrous graphene scaffolds exhibited tunable structures, maneuverable mechanical properties, and good electrical conductivity and biocompatibility, as reflected by the adhesion and proliferation of SH-SY5Y cells on the graphene microfibrous scaffolds in an obviously oriented manner. The developed M3DP would be a powerful tool for fabricating 3D graphene microfibrous scaffolds for electroactive tissue regeneration and drug-screening applications.

Many cell responses that underlie the development, maturation, and function of tissues are guided by the architecture and mechanical loading of the extracellular matrix (ECM). Because mechanical stimulation must be transmitted through the ECM architecture, the synergy between these two factors is important. However, recapitulating the synergy of these physical microenvironmental cues in vitro remains challenging. To address this, a 3D magnetically actuated collagen hydrogel platform is developed that enables combined control of ECM architecture and mechanical stimulation. With this platform, it is demonstrated how these factors synergistically promote cell alignment of C2C12 myoblasts and enhance myogenesis. This promotion is driven in part by the dynamics of Yes-associated protein and structure of cellular microtubule networks. This facile platform holds great promises for regulating cell behavior and fate, generating a broad range of engineered physiologically representative microtissues in vitro, and quantifying the mechanobiology underlying their functions.

The shortened Abstract is as follows: Therapeutic gas nitric oxide (NO) has demonstrated the unique advances in biomedical applications due to its prominent role in regulating physiological/pathophysiological activities in terms of vasodilation, angiogenesis, chemosensitizing effect, and bactericidal effect. However, it is challenging to deliver NO, due to its short half-life (

Myocardial tissue engineering offers a novel technology to improve or regenerate cardiac functions using a combination of cells, biomaterials and engineering strategies. Inspired by low-resistance pathways for electrical signal propagation in the native heart tissue, electrically conductive nanofibrous scaffolds composed of melanin, poly(L-lactide-co-e-caprolactone) and gelatin were fabricated to provide electrophysiological cues to cardiac myocytes and mimic the native myocardial environment. Our results show that by increasing the concentration of melanin to 40% within the composite, the fiber diameters reduced to 153 ± 30 nm, modulus decreased to 7.1 ± 0.6 MPa, and conductance increased to 259.51 ± 187.60 μS cm−1. Results of cell proliferation and immunostaining analysis of human cardiac myocytes demonstrated that the conductive nanofibers containing 10% melanin promote cell interaction with expression of cardiac-specific proteins compared to other scaffolds. Electrical stimulation through the scaffolds showed enhanced cell proliferation and the expression of connexin-43, signifying the potential of using melanin containing nanofibers as a suitable cardiac patch for the regeneration of infarct myocardium.

The potential for the use of electric stimulation to control cell behavior on a surface has been well documented. In terms of orthopaedic applications, there is a need to develop bioactive surfaces with a built-in electric field for clinically relevant materials, such as load-bearing titanium (Ti). In this work, a bi-layered SnO

Engineered tissue constructs rely on biomaterials as support structures for tissue repair and regeneration. Among these biomaterials, polyester biomaterials have been widely used for scaffold construction because of their merits such as ease in synthesis, degradable properties, and elastomeric characteristics. To mimic the aligned structures of native extracellular matrix (ECM) in tissues such as nerve, heart and tendon, various polyester materials have been fabricated into aligned fibrous scaffolds with fibers ranging from several nanometers to several micrometers in diameter by electrospinning in a simple and reproducible manner. These aligned fibrous scaffolds, especially the three-dimensional (3D) aligned nanofibrous scaffolds have emerged as a promising solution for tissue regeneration. Compared with two-dimensional (2D) scaffolds, the 3D aligned nanofibrous scaffolds provide another dimension for cell behaviors such as morphogenesis, migration and cell-cell interactions, which is important in regulating the stem cell fate and tissue regeneration. In this review, we provide an extensive overview on recent efforts for constructing 3D aligned polyester nanofibrous scaffolds by electrospinning, then the results of cell-specific functions dependent on such physical and chemical cues, and discuss their potentials in improving or restoring damaged tissues.

The poor osseointegration of Ti implant significantly compromise its application in load-bearing bone repair and replacement. Electrically bioactive coating inspirited from heterojunction on Ti implant can benefit osseointegration but cannot avoid the stress shielding effect between bone and implant. To resolve this conflict, hierarchically structured Ti implant with electrically bioactive SnO2-TiO2 bilayered surface has been developed to enhance osseointegration. Benefiting from the electric cue offered by the built-in electrical field of SnO2-TiO2 heterojunction and the topographic cue provided by the hierarchical surface structure to bone regeneration, the osteoblastic function of basic multicellular units around the implant is significantly improved. Because the individual TiO2 or SnO2 coating with uniform surface exhibits no electrical bioactivity, the effects of electric and topographic cues to osseointegration have been decoupled via the analysis of in vivo performance for the placed Ti implant with different surfaces. The developed Ti implant shows significantly improved osseointegration with excellent bone-implant contact, improved mineralization of extracellular matrix, and increased push-out force. These results suggest that the synergistic strategy of combing electrical bioactivity with hierarchical surface structure provides a new platform for developing advanced endosseous implants.

In vivo, cells are located in a dynamic, three-dimensional (3D) cell microenvironment, and various biomaterials have been used to engineer 3D cell microenvironments in vitro to study the effects of the cell microenvironment on the regulation of cell fate. However, conventional hydrogels can only mimic the static cell microenvironment without any synchronous regulations. Therefore, novel hydrogels that are capable of responding to specific stimuli (e.g., light, temperature, pH, and magnetic and electrical stimulations) have emerged as versatile platforms to precisely mimic the dynamic native 3D cell microenvironment. Among these novel hydrogels, photoresponsive hydrogels (PRHs) that are capable of changing their physical and chemical properties after exposure to light irradiation enable the dynamic, native cell microenvironment to be mimicked and show great promise in deciphering the unknown mechanisms of the 3D cell microenvironment in regulating the cell fate. Several reviews have already summarized the advances of PRHs and have focused on specific photosensitive chemical groups and photoresponsive elements or on the reaction categories and mechanism of PRHs. However, a holistic view of novel PRHs, which highlights the multiple physical and chemical properties that can be tuned by remote light activation, as well as their applications in engineering a dynamic cell microenvironment for the regulation of cell behaviors in vitro is still missing and is the focus of this review.

Triple-negative breast cancer (TNBC) does not respond to many targeted drugs due to the lack of three receptors (i.e., estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2), which makes it difficult for TNBC detection and treatment. As compared to traditional breast cancer treatments such as surgery and chemotherapy, photodynamic therapy (PDT) has emerged as a promising approach for treating TNBC due to its precise controllability, high spatiotemporal accuracy, and minimal invasive nature. However, traditional photosensitizers used in PDT are associated with limitations of aggregation-caused quenching (ACQ), and the ACQ induced a significant decrease in reactive oxygen species (ROS) generation. To address these, we synthesized a cyclic arginine-glycine-aspartic acid (cRGD) peptide-decorated conjugated polymer (CP) nanoparticles with poly[2-methoxy-5-(2-ethyl-hexyloxy)-1,4-phenylenevinylene] (MEH-PPV) as the photosensitizer for the theranostics of TNBC. The synthesized CP nanoparticles show bright fluorescence with high stability and could effectively produce ROS under light irradiation. Cell viability studies showed that the CP nanoparticles have negligible dark cytotoxicity and could efficiently kill the α

Fluorescence imaging is superior in sensitivity and resolution compared with other imaging modalities; however, its application is hindered by high background noise. Tissue-selective strategies, such as passive, active, and activatable targeting, hold great promise in accelerating clinical translation by significantly improving the tumor:background ratio (TBR) and, in turn, the sensitivity and contrast of fluorescence imaging. Compared with the 'always on' contrast agents, activatable probes, which remain nonfluorescent until being activated by tumor-specific molecular targets, further enhance TBR and at the same time provide additional molecular information that can be related to tumor staging and therapy response. In this review, we summarize recent advances in the development of activatable fluorescence probes and provide insights into their advantages and limitations when used for tumor imaging.

Tracking the distribution and degradation of hydrogels in vivo is important for various applications including tissue engineering and drug delivery. Among various imaging modalities, fluorescence imaging has attracted intensive attention due to their high sensitivity, low cost and easy operation. Particularly, upconversion nanoparticles (UCNPs) that emit visible lights upon near-infrared (NIR) light excitation as tracking probes are promising in deciphering the fate of hydrogels after transplantation. Herein, we reported a facile and non-invasive in vivo hydrogel tracking method using UCNPs, where the degradation of hydrogels was determined using the decrease in fluorescence intensity from the UCNPs encapsulated in the hydrogels. We found that the change in the fluorescence intensity from the UCNPs was well consistent with that of the fluorescein isothiocyanate (FITC) covalently conjugated to hydrogels and also with the weight change of the hydrogels, suggesting the accuracy of the UCNPs in tracking the degradation of hydrogels. Furthermore, the in vivo fluorescence signals were only observed from the UCNPs instead of FITC after implantation for 7 days due to the deep tissue penetration of UCNPs, demonstrating the capability of UCNPs in longitudinal, consecutive and non-invasive monitoring the in vivo degradation of hydrogels without causing any damage to the major organs (heart, lung, liver and kidney) of model rats. This study thus paves the way for monitoring the in vivo behaviors of biomimetic materials via deep tissue imaging with great clinical translation potentials. Statement of Significance Long-term noninvasive in vivo tracking of the distribution and degradation of biodegradable hydrogels using fluorescent probes is important in tissue regeneration and drug delivery. Unlike the widely used fluorescent dyes and quantum dots (QDs) that suffer from photobleaching and undesired toxicity, upconversion nanoparticles (UCNPs) with high stability, deep tissue penetration as tracking probes are promising in deciphering the fate of hydrogels after transplantation. Herein, we reported a noninvasive in vivo hydrogel tracking method using UCNPs and found that the fluorescence intensity change from the UCNPs was well consistent with the weight change of the hydrogels, suggesting the accuracy of UCNPs in tracking hydrogel degradation. This study provides inspirations on developing advanced NIR light regulated probes with great clinical translation potentials.

A modified energy transfer model by incorporating self-quenching effect is introduced to determine upconversion emission of β-NaYF 4 :Yb,Er. The simulation results agree well with existing experimental results, demonstrating the critical role of self-quenching effect in upconversion emission. Our results confirm that a 4.4-fold increase of green upconversion and 86-fold increase in the intensity of red upconversion emission could be realized by suppressing self-quenching. In addition, the optimal doping concentrations for integral emission intensity are found to be independent of excitation power, while the green to red ratio is found to rely significantly on excitation power. Our model offers mechanistic insight into upconversion emission processes and provides inspirations in improving upconversion emission efficiency through optimization of energy transfer pathways in different types of matrix sub-lattice.

Stem cell therapy holds great promise for cardiac regeneration. However, the lake of controllability in stem cell fate after in vivo transplantation greatly restricts the therapeutic outcomes of stem cell therapy. MicroRNA transfection has emerged as a powerful tool to control stem cell fate for enhanced cardiac regeneration. However, the clinical translation of therapy based on gene-transfected stem cells remains challenging, due to the unknown in vivo behaviors of stem cells. Here, we developed a novel nano-platform (i.e., PFBT@miR-1-Tat NPs) that can achieve triggered release of microRNA-1 for promoting cardiac differentiation of mesenchymal stem cells (MSCs), and long-term tracking of transplanted MSCs through the bright and ultra-stable fluorescence of conjugated polymer poly(9,9-dioctylfluorene-alt-benzothiadiazole) (PFBT). We found that PFBT@miR-1-Tat NP-transfected MSC treatment significantly restore infarcted myocardium through promoting stem cell cardiac differentiation and integration with the in-situ cardiac tissues. While, MSCs without gene transfection improve the infarcted heart functions mainly through paracrine effect and blood vessel formation. The developed conjugated polymer nanovector would be a powerful tool in manipulating as well as revealing the fate of therapeutic cells in vivo, which is critical for optimizing the therapeutic route of gene and cell combined therapy and therefore for accelerating clinical translation.

Extracellular matrix remodeling is essential for the development and functions of connective tissues (e.g., heart, muscle and periodontal ligament), where ECM is generally with highly anisotropic features and under mechanical stimulation. However, the nature of how cells remodel their surrounding ECM under mechanical stimulation remains elusive. Herein, we encapsulated human periodontal ligament stem cells (hPDLSCs) within the aligned rat collagen scaffold labeled with fluorescein isothiocyanate (FITC) and provided continuous mechanical stimulation by magnetic stretching. Through tracking the FITC-labeled rat collagen scaffold and the newly secreted human type I collagen, we studied the mechanism of aligned ECM remodeling by encapsulated cells under mechanical stretching. We found that the aligned topography combined with magnetic stretching could significantly promote initial ECM degradation and new ECM secretion: the expression of matrix metalloproteinase 1 and 9 are significantly higher, and the elastic modulus increases from 50 kPa to 75 kPa as compared to the random collagen scaffold encapsulating hPDLSCs. Therefore, we decipher that cells remodel their surrounding ECM under continuous stretching through degradation and then secretion of new ECM to integrate with the aligned ECM and maintain tissue functions. Our study holds great potential in optimization of biomaterial scaffold design for clinical translation.

Stem cell therapy holds great promise for cardiac regeneration. However, the lack of ability to control stem cell fate after in vivo transplantation greatly restricts its therapeutic outcomes. MicroRNA delivery has emerged as a powerful tool to control stem cell fate for enhanced cardiac regeneration. However, the clinical translation of therapy based on gene-transfected stem cells remains challenging, due to the unknown in vivo behaviors of stem cells. Here, we developed a nano-platform (i.e., PFBT@miR-1-Tat NPs) that can achieve triggered release of microRNA-1 to promote cardiac differentiation of mesenchymal stem cells (MSCs), and long-term tracking of transplanted MSCs through bright and ultra-stable fluorescence of conjugated polymer poly(9,9-dioctylfluorene-alt-benzothiadiazole) (PFBT). We found that PFBT@miR-1-Tat NP-treated MSCs significantly restored the infarcted myocardium by promoting stem cell cardiac differentiation and integration with the in situ cardiac tissues. Meanwhile, MSCs without gene delivery improved the infarcted heart functions mainly through a paracrine effect and blood vessel formation. The developed conjugated polymer nanovector should be a powerful tool for manipulating as well as revealing the fate of therapeutic cells in vivo, which is critical for optimizing the therapeutic route of gene and cell combined therapy and therefore for accelerating clinical translation. STATEMENT OF SIGNIFICANCE: The lack of controllability in stem cell fate and the unclear in vivo cellular behaviors restrict the therapeutic outcomes of stem cell therapy. Herein, we engineered fluorescent conjugated polymer nanoparticles as gene delivery nanovectors with controlled release and high intracellular delivery capability to harness the fate of mesenchymal stem cells (MSCs) in vivo, meanwhile to reveal the cellular mechanism of gene-treated stem cell therapy. As compared with only MSC treatment that improves infarcted myocardium functions through paracrine effect, treatment with conjugated polymer nanovector-treated MSCs significantly restored infarcted myocardium through enhancing MSC cardiac differentiation and integration with the in-situ cardiac tissues. These findings demonstrate that the conjugated polymer nanovector would be a powerful tool in optimizing gene and cell combined therapy.

3D bioprinting has been developed to effectively and rapidly pattern living cells and biomaterials, aiming to create complex bioconstructs. However, placing biocompatible materials or cells into direct contact via bioprinting is necessary but insufficient for creating these constructs. Therefore, '4D bioprinting' has emerged recently, where 'time' is integrated with 3D bioprinting as the fourth dimension, and the printed objects can change their shapes or functionalities when an external stimulus is imposed or when cell fusion or postprinting self-assembly occurs. In this review, we highlight recent developments in 4D bioprinting technology. Additionally, we review the uses of 4D bioprinting in tissue engineering and drug delivery. Finally, we discuss the major roadblocks to this approach, together with possible solutions, to provide future perspectives on this technology.

Mesenchymal stem cells (MSCs) hold great promise as cell therapy candidate in clinics. However, the underlying mechanisms remain elusive due to the lack of effective cell tracking approaches during therapeutic processes. In this study, we successfully synthesized and utilized NaYF 4 :Yb 3+ ,Er 3+ upconversion nanoparticles (UCNPs) to label and track rabbit bone marrow mesenchymal stem cells (rBMSCs) during the osteogenic differentiation in vitro . To improve their biocompatibility and cellular uptake, we modified the UCNPs with negatively-charged poly(acrylic acid) and positively-charged poly(allylamine hydrochloride) in turns ( i.e. , PAH-PAA-UCNPs). The effect of cellular uptake of UCNPs on the osteogenic differentiation of rBMSCs was systematically evaluated, and no significant difference was found between rBMSCs labeled with UCNPs (concentration range of 0–50 μg/mL) and UCNPs-free rBMSCs in terms of cell viability, ALP activity, osteogenic protein expressions and production of mineralized nodules. Moreover, the PAH-PAA-UCNPs at a concentration of 50 μg/mL exhibited the highest biocompatibility and stability, which could well track rBMSCs during the osteogenesis process. These results would provide a positive reference for the application of these lanthanide-doped UCNPs as fluorescent nanoprobes for stem cell tracking to further understand the mechanism of stem cell fate in tissue engineering and stem cell therapy. Statement of Significance Upconversion nanoparticles (UCNPs) have attracted increasing attention as alternative probes for tracking various types of cells including stem cells. The reported fluorapatite-based UCNPs with the needle-like morphology showed a little poor performance on stem cell tracking, which was possibly attributed to the low upconversion efficiency and cell labeling efficiency potentially due to nanomaterial composition, crystal structure and shape. Here, we synthesized the positively-charged NaYF 4 :Yb 3+ ,Er 3+ UCNPs with hexagonal phase and sphere-like morphology to enhance their upconversion efficiency, biocompatibility and cellular uptake, leading to a successful tracking of rBMSCs in osteogenesis process without impairing cell viability and differentiation capacity. This study provided a necessary reference for the application of UCNPs in stem cell tracking to better understand the mechanism of stem cell fate in tissue engineering, stem cell therapy, etc .

In article number 2001820, Feng Xu and co‐workers report a multifunctional hydrogel‐based liquid bandage (LBA) for trauma emergency; the resulting photo‐responsive chitosan‐based hydrogel harvests robust adhesive, hemostatic, and antibacterial performances as a first‐aid tissue adhesive. LBA is simply prepared without any extraneous photo‐initiator and toxic crosslinking agent for its safe use. Moreover, the utilization of this LBA can boost wound healing.

Photodynamic therapy (PDT) has been widely applied in the clinic for the treatment of various types of cancer due to its precise controllability, minimally invasive approach and high spatiotemporal accuracy as compared with conventional chemotherapy. However, the porphyrin-based photosensitizers (PSs) used in clinics generally suffer from aggregation-caused reductions in the generation of reactive oxygen species (ROS) and limited tissue penetration because of visible light activation, which greatly hampers their applications for the treatment of deep-seated tumors. Methods: We present a facile strategy for constructing a NIR-regulated cancer theranostic nanoplatform by encapsulating upconversion nanoparticles (UCNPs) and a luminogen (2-(2,6-bis((E)-4-(phenyl(40-(1,2,2-triphenylvinyl)-[1,10-biphenyl]-4-yl)amino)styryl)-4H-pyran-4-ylidene)malononitrile, TTD) with aggregation-induced emission (AIEgen) characteristics using an amphiphilic polymer, and further conjugating cyclic arginine-glycine-aspartic acid (cRGD) peptide to yield UCNP@TTD-cRGD NPs. We then evaluated the bioimaging and anti-tumor capability of the UCNP@TTD-cRGD NPs under NIR light illumination in an in vitro three-dimensional (3D) cancer spheroid and in a murine tumor model, respectively. Results: With a close match between the UCNP emission and absorption of the AIEgen, the synthesized NPs could efficiently generate ROS, even under excitation through thick tissues. The NIR-regulated UCNP@TTD-cRGD NPs that were developed could selectively light up the targeted cancer cells and significantly inhibit tumor growth during the NIR-regulated PDT treatment as compared with the cells under white light excitation. Conclusion: In summary, the synthesized UCNP@TTD-cRGD NPs showed great potential in NIR light-regulated photodynamic therapy of deep-seated tumors. Our study will inspire further exploration of novel theranostic nanoplatforms that combine UCNPs and various AIEgen PSs for the advancement of deep-seated tumor treatments with potential clinical translations.

Stem cell therapy is promising for treating traumatic injuries of the central nervous system, where a major challenge is to effectively differentiate neural stem cells into neurons with uniaxial alignment. Recently, controlling stem cell fate by modulating biophysical cues (e.g., stiffness, conductivity, and patterns) has emerged as an attractive approach. Herein, we report a new heterostructure composite scaffold to induce cell-oriented growth and enhance the neuronal differentiation of SH-SY5Y cells. The scaffold is composed of aligned electrospinning silk nanofibers coated on reduced graphene paper with high conductivity and good biocompatibility. Our experimental results demonstrate that the composite scaffold can effectively induce the oriented growth and enhance neuronal differentiation of SH-SY5Y cells. Our study develops a novel scaffold for enhancing the differentiation of SH-SY5Y cells into neurons, which holds great potential in the treatment of neurological diseases and injuries.

The poor osseointegration of Ti implant significantly compromise its application in load-bearing bone repair and replacement. Electrically bioactive coating inspirited from heterojunction on Ti implant can benefit osseointegration but cannot avoid the stress shielding effect between bone and implant. To resolve this conflict, hierarchically structured Ti implant with electrically bioactive SnO

Medicine counterfeiting is a serious issue worldwide, involving potentially devastating health repercussions. Advanced anti-counterfeit technology for drugs has therefore aroused intensive interest. However, existing anti-counterfeit technologies are associated with drawbacks such as the high cost, complex fabrication process, sophisticated operation and incapability in authenticating drug ingredients. In this contribution, we developed a smart phone recognition based upconversion fluorescent three-dimensional (3D) quick response (QR) code for tracking and anti-counterfeiting of drugs. We firstly formulated three colored inks incorporating upconversion nanoparticles with RGB (i.e., red, green and blue) emission colors. Using a modified inkjet printer, we printed a series of colors by precisely regulating the overlap of these three inks. Meanwhile, we developed a multilayer printing and splitting technology, which significantly increases the information storage capacity per unit area. As an example, we directly printed the upconversion fluorescent 3D QR code on the surface of drug capsules. The 3D QR code consisted of three different color layers with each layer encoded by information of different aspects of the drug. A smart phone APP was designed to decode the multicolor 3D QR code, providing the authenticity and related information of drugs. The developed technology possesses merits in terms of low cost, ease of operation, high throughput and high information capacity, thus holds great potential for drug anti-counterfeiting.

The development of functional polymers from renewable lignin is attractive due to the depletion of fossil fuel and increasing environmental usage. A series of poly(ethylene glycol) methyl ether methacrylate (PEGMA)-grafted lignin hyperbranched copolymers were prepared by atom transfer radical polymerization (ATRP). The chemical structures, molecular characteristic and thermal properties of these copolymers were evaluated and such copolymers were prepared in a range of molecular weights from 38.7 to 65.0 kDa by adjusting the PEGMA-to-lignin weight ratio. As a result from their hyperbranch architecture, their aqueous solutions were found to form supramolecular hydrogels with a very low critical gelation concentration of 1 wt % copolymers, in the presence of α-cyclodextrin (α-CD). The rheological properties of the supramolecular assemblies were investigated and these hydrogel systems showed tunable mechanical response and excellent self-healing capability. Combined with good biocompatibility, these new types...

The potential for the use of electric stimulation to control cell behavior on a surface has been well documented. In terms of orthopaedic applications, there is a need to develop bioactive surfaces with a built-in electric field for clinically relevant materials, such as load-bearing titanium (Ti). In this work, a bi-layered SnO2-TiO2 coating is fabricated via microarc oxidation and subsequent hydrothermal treatment to adjust the surface electrical properties for improving bioactivity. An oxidized titanium interlayer on Ti substrate allows the growth of SnO2 nanorods with different morphologies, which leads to a built-in n-n heterojunction of SnO2 and TiO2 on the Ti surface with varied surface electrical properties. The crystallization of the TiO2 interlayer facilitates the growth of SnO2 nanorods, showing excellent hydrophilicity and good apatite-inducing ability due to the formation of a heterojunction. The results suggest that the bi-layered SnO2-TiO2 coating with electrically stimulated bioactivity could provide a novel way to enhance osteointegration on the Ti surface.

Heart disease, especially myocardial infarction (MI), has become the leading cause of death all over the world, especially since the myocardium lacks the ability to regenerate after infarction. The capability of mesenchymal stem cells (MSCs) to differentiate into the cardiac lineage holds great potential in regenerative medicine for MI treatment. In this study, we investigated the potential of human MSCs (hMSCs) to differentiate into cardiomyogenic cell lineages, using 5-azacytidine (5-aza) on electrospun poly(e-caprolactone)-gelatin (PCL-gelatin) nanofibrous scaffolds. Immunofluorescence staining analysis showed that after 15 days of in vitro culture the hMSCs differentiated to cardiomyogenic cells on PCL-gelatin (PG) nanofibers and expressed a higher level of cardiac-specific proteins, such as α-actinin and troponin-T, compared to the MSC-differentiated CMs on tissue culture plates (control). To further induce the cardiac differentiation, vascular endothelial growth factor (VEGF) was incorporated into the nanofibers by blending or co-axial electrospinning, and in vitro release study showed that the growth factor could cause sustained release of VEGF from the nanofibers for a period of up to 21 days. The incorporation of VEGF within the nanofibers improved the proliferation of MSCs and, more importantly, enhanced the expression of cardiac-specific proteins on PG-VEGF nanofibers. Our study demonstrated that the electrospun PG nanofibers encapsulated with VEGF have the ability to promote cardiac differentiation of hMSCs, and might be promising scaffolds for myocardial regeneration. Copyright © 2015 John Wiley & Sons, Ltd.

The cell microenvironment has emerged as a key determinant of cell behavior and function in development, physiology, and pathophysiology. The extracellular matrix (ECM) within the cell microenvironment serves not only as a structural foundation for cells but also as a source of three-dimensional (3D) biochemical and biophysical cues that trigger and regulate cell behaviors. Increasing evidence suggests that the 3D character of the microenvironment is required for development of many critical cell responses observed in vivo, fueling a surge in the development of functional and biomimetic materials for engineering the 3D cell microenvironment. Progress in the design of such materials has improved control of cell behaviors in 3D and advanced the fields of tissue regeneration, in vitro tissue models, large-scale cell differentiation, immunotherapy, and gene therapy. However, the field is still in its infancy, and discoveries about the nature of cell-microenvironment interactions continue to overturn much early progress in the field. Key challenges continue to be dissecting the roles of chemistry, structure, mechanics, and electrophysiology in the cell microenvironment, and understanding and harnessing the roles of periodicity and drift in these factors. This review encapsulates where recent advances appear to leave the ever-shifting state of the art, and it highlights areas in which substantial potential and uncertainty remain.

• Summary of recent advances in the development of therapeutic nanomaterials and their applications for cancer diagnosis, drug delivery and tissue regeneration.

Recent progress in tissue-engineered skin grafts has alleviated the demand for autologous split thickness skin grafts for treatment of large skin wounds. In this study, a series of cost-effective nanofibrous scaffolds aimed at full-thickness wound healing are fabricated by blending gelatin (Gel) with poly(l-lactic acid)-b-poly( ε-caprolactone) (PLLCL) and electrospun to obtain composite Gel/PLLCL nanofibers in four different weight ratios (w/w) of 80:20 [Gel/PLLCL(20)], 70:30 [Gel/PLLCL(30)], 60:40 [Gel/PLLCL(40)], and 50:50 [Gel/PLLCL(50)]. The mechanical properties of these nanofibrous scaffolds were evaluated in both dry and wet conditions, and the Gel/PLLCL(40) retained suitable tensile stress (1.16 ± 0.03 MPa) to be handled even in wet conditions. Moreover, the proliferations of fibroblast cells on Gel/PLLCL(40) were 15%, 7% and 10% higher compared to cell proliferations on Gel/PLLCL(20), Gel/PLLCL(30), and Gel/PLLCL(50), respectively. In vitro results confirmed Gel/PLLCL(40) as the optimized scaffold composition suitable for skin tissue engineering. The healing ability of this scaffold was studied in vivo using mouse models. The Gel/PLLCL(40) greatly accelerated wound closure and regeneration occurring in the first 10 days of implantation compared to the control group. In addition, newly regenerated epidermis was only found in the nanofibrous scaffolds–treated group, and it was comparable to the epidermis of normal skin.

A series of thermo-responsive amphiphilic hybrid copolymers with a random brush-like structure were synthesized by copolymerizing hydrophilic poly(ethylene glycol)methacrylate (PEGMA) and hydrophobic polyhedral oligomeric silsesquioxane methacrylate (POSSMA) together with temperature sensitive poly(propylene glycol)methacrylate (PPGMA) via atom transfer radical polymerization (ATRP). The resulting poly(PEGMA–PPGMA–POSSMA) (PEPS) hybrid copolymers show a lower critical solution temperature (LCST) in the range of 31–33 °C. Static and dynamic light scattering (SLS and DLS) studies show that micellar structures created by the PEPS copolymer in aqueous media were core-shell structures and possessed a thick hydration layer. The presence of a small amount of POSS (3.1 wt%) in the PEPS copolymers lowered the CMC of the micelles at room temperature by one order of magnitude compared to samples without POSSMA (PEP). Incorporation of POSSMA also enhanced the stability of the formed micelles, i.e. PEPS containing 6.7 wt% POSS exhibited a constant hydrodynamic radius, Rh (∼65 nm), and an aggregation number, Nagg (∼350), when the temperature was varied from 20 to 70 °C while PEP without POSS showed a large increase in both Rh and Nagg values. On the other hand, the change of Rg as the temperature increases could be attributed to the PPG brush adopting a more extended and compact conformation below and above LCST respectively. The thermo-responsiveness of the PPG brush in PEPS hybrid micelles was also exploited to mimic the natural GroEL–GroES chaperone functionalities for renaturation of thermally denatured proteins. Above LCST of PPG, the chaperone-like system comes into effect with hydrophobic PPG domains on the micelle surface, providing spontaneous capture and protection of the unfolded proteins, thus inhibiting the undesired protein aggregation at elevated temperatures. Upon cooling, PPG returns to its hydrophilic state, thereby inducing the release of the bound unfolded proteins. The renaturation process of the detached proteins is spontaneously accomplished by the presence of PEG and OH-groups in the micelle corona. The working mechanism and thermal denaturation protection effect were also investigated by DLS, SLS and circular dichroism (CD) spectroscopy. In the presence of PEPS hybrid micelles, the protection efficiencies for GFP, lipase and lysozyme that can be achieved during the heat-induced denaturation process are 81.4%, 89.3% and 88.7%, respectively. Cell culture and cytotoxicity studies revealed that the PEPS hybrid micelles could be effectively internalized by C6 glioma cells and possess good cell biocompatibility. These interesting findings open up new opportunities to exploit PEPS hybrid copolymers as artificial chaperones for protecting unfolded proteins from toxic aggregation at high temperatures.

Regeneration of bone and cartilage tissues has been an important issue for biological repair in the field of regenerative medicine. The rapidly emerging field of tissue engineering holds great promise for repair and generation of functional bone and cartilage substitutes with a combination of biomaterials, cells, drugs and growth factors. Scaffolds play a pivotal role in tissue engineering as they mimic the natural extracellular matrix (ECM) and play an important role in guiding cell adhesion and proliferation, and maintaining the normal phenotype of the tissues. The use of tissue-engineered grafts based on scaffolds has found to be a more effective method than conventional implantations of autograft, allograft, xenograft. In recent years much attention has been given to electrospinning as a feasible and versatile technique for fabrication of nanofibrous scaffolds, with large surface area to volume ratio, high porosity, mechanical properties and physical dimension similar to the ECM of natural tissues. Extensive research has been carried out for fabrication polymeric nanofibrous substrates with incorporation of hydroxyapatite nanoparticles or bone morphogenetic protein molecules for efficient tissue repair. Here we review on the literature of electrospun nanofibrous scaffolds, their modifications, and advances aimed towards the rapid regeneration of bone and cartilage.