A universal and facile approach to modifying proteins so that they can rapidly form hydrogel upon mixing with crosslinkers is presented. The concept of it is to introduce maleimide, which is highly reactive with dithiol-containing crosslinkers via thiol-ene click chemistry, onto proteins. Bovine serum albumin (BSA) is used as a model protein due to its good stability and low cost. The results here show that a protein hydrogel can be readily formed by blending modified BSA and resilin-related peptide crosslinker solutions at a proper ratio. The hydrogel exhibits good elasticity and tunable mechanical as well as biochemical properties. Moreover, it allows convenient 3D cell encapsulation and shows good biocompatibility. Muscle cells embedded in the hydrogel are promoted to spread by incorporating arginyl-glycyl-aspartic acid (RGD)-containing peptide into the system, thus warranting a bright future of it in regenerative medicine.

Engineering living tissues that simulate their natural counterparts is a dynamic area of research. Among the various models of biological tissues being developed, fiber-shaped cellular architectures, which can be used as artificial blood vessels or muscle fibers, have drawn particular attention. However, the fabrication of continuous microfiber substrates for culturing cells is still limited to a restricted number of polymers (e.g., alginate) having easy processability but poor cell–material interaction properties. Moreover, the typical smooth surface of a synthetic fiber does not replicate the micro- and nanofeatures observed in vivo, which guide and regulate cell behavior. In this study, a method to fabricate photocrosslinkable cell-responsive methacrylamide-modified gelatin (GelMA) fibers with exquisite microstructured surfaces by using a microfluidic device is developed. These hydrogel fibers with microgrooved surfaces efficiently promote cell encapsulation and adhesion. GelMA fibers significantly promote the viability of cells encapsulated in/or grown on the fibers compared with similar grooved alginate fibers used as controls. Importantly, the grooves engraved on the GelMA fibers induce cell alignment. Furthermore, the GelMA fibers exhibit excellent processability and could be wound into various shapes. These microstructured GelMA fibers have great potential as templates for the creation of fiber-shaped tissues or tissue microstructures.

As a technique for precisely manipulating fluid at the micrometer scale, the field of microfluidics has experienced an explosive growth over the past two decades, particularly owing to the advances in device design and fabrication. With the inherent advantages associated with its scale of operation, and its flexibility in being incorporated with other microscale techniques for manipulation and detection, microfluidics has become a major enabling technology, which has introduced new paradigms in various fields involving biological cells. A microfluidic device is able to realize functions that are not easily imaginable in conventional biological analysis, such as highly parallel, sophisticated high-throughput analysis, single-cell analysis in a well-defined manner, and tissue engineering with the capability of manipulation at the single-cell level. Major advancements in microfluidic device fabrication and the growing trend of implementing microfluidics in cell studies are presented, with a focus on biological research and clinical diagnostics.

Gold nanocrystals and nanoassemblies have attracted extensive attention for various applications, including chemical and biological sensing, solar energy harvesting, and plasmon-enhanced spectroscopies, due to their unique plasmonic properties. It is of great importance to prepare shape-controlled Au nanocrystals with high monodispersity over a large range of sizes. In this work, Au nanospheres with sizes ranging from 20 nm to 220 nm are prepared using a simple seed-mediated growth method aided with mild oxidation. As-prepared Au nanospheres are remarkably uniform in size. The resultant Au nanospheres of different sizes are ideal building blocks for constructing plasmonic nanoassemblies. Core/satellite nanostructures are assembled out of differently sized Au nanospheres with molecular linkers. The core/satellite nanostructures show a red-shifted plasmon resonance peak in comparison to that of the Au cores, which is consistent with the results calculated according to Mie theory. As predicted by finite-difference time-domain simulations, the assembled core/satellite nanostructures exhibit strongly enhance Raman signals. This facile growth of Au nanospheres and assembly of core/satellite nanostructures are expected to facilitate the design of new nanoassemblies with desired plasmonic properties and functions.

Graphene, a two-dimensional, single-atom-thick carbon crystal arranged in a honeycomb lattice, shows extraordinary electronic, mechanical, thermal, optical, and optoelectronic properties, and has great potential in next-generation electronics, optics, and optoelectronics. Graphene and graphene-based nanomaterials have witnessed a very fast development of both fundamental and practical aspects in optics and optoelectronics since 2008. In this Feature Article, the synthesis techniques and main electronic and optical properties of graphene-based nanomaterials are introduced with a comprehensive view. Recent progress of graphene-based nanomaterials in optical and optoelectronic applications is then reviewed, including transparent conductive electrodes, photodetectors and phototransistors, photovoltaics and light emitting devices, saturable absorbers for ultrafast lasers, and biological and photocatalytic applications. In the final section, perspectives are given and future challenges in optical and optoelectronic applications of graphene-based nanomaterials are addressed.

Magnesium-based metallic glasses (MMGs) show intriguing potentials for application as implantable biomaterials owing to their disordered atomic structure, good biodegradability, low elastic modulus, high strength, and large elasticity. However, despite of all these advantages, their brittleness is their Achilles’ heel, which severely limits their application as biomedical materials. In the current study, a significantly improved ductility of MMGs under bending and tensile loading through minor alloying with rare-earth element ytterbium (Yb) at an atomic concentration of 2 and 4% is reported. The enhanced ductility is attributed to the increased density of shear bands close to fracture end and larger plastic zones on the fracture surface. In comparison with that of Yb-free control, in vitro cell culture study confirms an improved biocompatibility of MMGs alloyed with Yb as determined by MTT, live-dead, and cytoskeleton staining assays, respectively.

Elaborating a bone replacement using tissue-engineering strategies for bone repair seems to be a promising remedy. However, previous platforms are limited in constructing three-dimensional porous scaffolds and neglected the critical importance of periosteum (a pivotal source of osteogenic cells for bone regeneration). We report here an innovative method using the periosteum as a template to replicate its exquisite morphologies onto the surfaces of biomaterials. The precise topographic cues (grooved micropatterns) on the surface of collagen membrane inherited from the periosteum effectively directed cell alignment as the way of natural periosteum. Besides, we placed the stem-cell and endothelial-cell-laden collagen membrane (pseudo-periosteum) onto a three-dimensional porous scaffold. The pseudo-periosteum-covered scaffolds showed remarkable osteogenesis when compared with the pseudo-periosteum-free scaffolds, indicating the significant importance of pseudo-periosteum on bone regeneration. This study gives a novel concept for the construction of bone tissue engineering scaffold and may provide new insight for periosteum research.

Injury to articular cartilage, especially the defects induced by degenerative diseases has presented insurmountable challenges. Elaborating a replacement of articular cartilage using biomimic tissue-engineering strategies provides a promising remedy. However, none of the previous osteo/chondrogenic methodologies can not only simultaneously induce osteo/chondrogenesis of stem cells in one scaffolding niche, but also generate a biomimic interface between the formed osteogenic and chondrogenic zones. We report here an innovative method using biomicrofluidic techniques to simultaneously steer distinct specialized differentiation of stem cells into chondrocytes and osteoblasts in one hydrogel slab. Importantly, a gradient that mimics the interface of bone-to-cartilage was generated in the middle of the hydrogel slab. We compared this format with the conventional method for osteochondrogenesis; this format using the gradient-generating microfluidic device indicated outstanding superiorities in stem cell culture and differentiation. Our findings will have a major impact on the design of versatile biomicrofluidic devices for interfacial tissue regeneration.

Human bone tissue is built in a hierarchical way by assembling various cells of specific functions; the behaviors of these cells in vivo are sophisticatedly regulated. However, the cells in an injured bone caused by tumor or other bone-related diseases cannot properly perform self-regulation behaviors, such as specialized differentiation. To address this challenge, a simple one-step strategy for patterning drug-laden poly(lactic-co-glycolic acid) (PLGA) microspheres into grooves by Teflon chips is developed to direct cellular alignment and osteogenic commitment of adipose-derived stem cells (ADSCs) for bone regeneration. A hydrophilic model protein and a hydrophobic model drug are encapsulated into microsphere-based grooved micropatterns to investigate the release of the molecules from the PLGA matrix. Both types of molecules show a sustained release with a small initial burst during the first couple of days. Osteogenic differentiated factors are also encapsulated in the micropatterns and the effect of these factors on inducing the osteogenic differentiation of ADSCs is studied. The ADSCs on the drug-laden micropatterns show stronger osteogenic commitment in culture than those on flat PLGA film or on drug-free grooved micropatterns cultured under the same conditions. The results demonstrate that a combination of chemical and topographical cues is more effective to direct the osteogenic commitment of stem cells than either is alone. The microsphere-based groove micropatterns show potential for stem cell research and bone regenerative therapies.

Understanding the effect of graphene on cellular behavior is important for enabling a range of new biological and biomedical applications. However, due to the complexity of cell responses and graphene surface states, regulating cellular behaviors on graphene or its derivatives is still a great challenge. To address this challenge we have developed a novel, facile route to regulate the cellular behaviors on few-layer reduced graphene oxide (FRGO) films by controlling the reduction states of graphene oxide. Our results indicate that the surface oxygen content of FRGO has a strong influence on cellular behavior, with the best performance for cell attachment, proliferation and phenotype being obtained in moderately reduced FRGO. Cell performance decreased significantly as the FRGO was highly reduced. Moderate performance was found in non-reduced pure graphene oxide and control glass slides. Our results highlight the important role of surface physicochemical characteristics of graphene and its derivatives in their interactions with biocomponents, and may have great potential in enabling the utility of graphene based materials in various biomedical and bioelectronic applications.

This work describes a convenient method to generate a poly(dimethylsiloxane) (PDMS) composite containing ZnO quantum dots (QDs) for whole-chip temperature measurements. This composite is highly fluorescent and very sensitive to temperature changes (0.4 nm °C⁻¹, compared to 0.1 nm °C⁻¹ in commonly used CdSe QDs). It also shows extremely high fluorescent stability under various conditions over long time without phase separation or fluorescent changes. Both merits make this composite an ideal material for sensing temperature changes on microfluidic chips. The bonding between the QDs and PDMS is studied by comparing PDMS composites with ZnO QDs of different sizes, and a model is given to elucidate the high stability of this composite.