Functionally graded surfaces and materials, featuring spatial variations in terms of composition, structure, and other properties across distance, have emerged as powerful platforms for mimicking native tissue architectures and enabling a wide range of biomedical applications. This review aims to provide a comprehensive overview of their fabrication methods and biomedical applications. We begin by introducing the concept of gradients and their inherent biological relevance in nature. With a distinct focus on either surfaces or materials, we then discuss the fabrication methods and characterization techniques capable of controlling the graded profiles. Importantly, representative examples are provided to highlight how engineered gradients regulate specific cellular responses and functionalities in biomedical contexts. Despite significant progress, challenges remain in translating laboratory-scale fabrication to clinical use, such as ensuring good reproducibility and scalability. At the end, we discuss how computational modeling and artificial intelligence offer new opportunities to address these challenges. We hope this review provides a framework for advancing the development of next-generation functionally graded surfaces and materials toward diverse biomedical applications.

Silver nanocubes have emerged as a model system for understanding how surface chemistry governs shape-controlled synthesis and shape preservation, in addition to their widespread use in a range of applications. This review discusses our recent progress in directly probing the surface of Ag nanocubes, with emphasis on surface-enhanced Raman scattering studies carried out under actual experimental conditions. We first discuss how the native surface is established during polyol synthesis, where chemisorbed chloride and poly(vinylpyrrolidone) act cooperatively to define and stabilize the cubic shape. We then show that sample collection, washing, and redispersion also reorganize the surface and determine whether the Ag nanocubes can retain their shape during storage. We also examine aqueous seed-mediated growth, in which rapid ligand exchange, transient AgCl formation, interfacial electron transfer, and surface reduction collectively govern the enlargement of Ag nanocubes. Taken together, these studies provide a mechanistic framework for rational synthesis of colloidal metal nanocrystals with controlled sizes and shapes.

Pathways and structural dynamics of phase transformations impact performance of materials in energy and information storage technologies. Palladium hydride (PdHx) nanocrystals are an ideal model system for studying solute-induced phase transformations, where elastic energy from lattice mismatch between α-PdHx and β-PdHx phases is often considered a key to determining the transformation pathways. α/β-PdHx interfacial elastic energy is affected by the confined geometry of a nanocrystal. However, how nanocrystal geometry influences phase transformation pathways is largely unknown. Using in situ liquid phase transmission electron microscopy, we directly visualize hydrogenation in Pd nanocrystals with two geometries, a nanocube and a hexagonal nanoplate. Both follow similar sequences of an initially curved nucleus, interface flattening, and reverse-stage nucleation; however, their evolving α/β-PdHx interfaces exhibit geometry-dependent crystallographic alignments. In nanocubes, {100}-aligned configurations conform to static elastic energy ordering, representing a pathway that maintains a local mechanical equilibrium, whereas nanoplates display both {110}- and {211}-aligned interfaces. Theoretical simulations show that geometry determines the accessibility of alternative phase transformation pathways as the system is driven far from equilibrium during hydrogenation. These findings identify geometry as a fundamental parameter for directing phase transformation pathways, offering design principles for accessing atypical configurations and improving properties of intercalation-based devices.

High-entropy alloy (HEA) nanocrystals, characterized by four core effects, including high entropy, lattice distortion, sluggish diffusion, and cocktail mixing, represent a transformative class of catalytic materials that combine compositional diversity with nanoscale complexity. By combining five or more elements into single-phase solid solutions, HEA nanocrystals offer unique opportunities to tailor local atomic environments, electronic structures, and catalytic properties. This Review offers a comprehensive overview of recent advances in the syntheses, compositional and structural controls, and catalytic applications of these materials, with a focus on achieving uniform atomic mixing and well-defined surface structures. We start with key synthetic methodologies, including both top-down and bottom-up approaches, and highlight wet-chemical synthesis that allows for precise regulation of reduction, nucleation, growth, and alloying dynamics to overcome challenges such as reduction kinetics, elemental immiscibility, and crystallographic incompatibility. We then discuss advanced characterization techniques and theoretical modeling approaches used to probe the multicomponent solid-solution phases, local coordination environments, interelement interactions, and synergistic effects that collectively govern the catalytic behaviors of HEA nanocrystals. We further highlight how these fundamental features manifest at the nanoscale to enhance performance across diverse catalytic reactions, including electro-, thermo-, and photocatalysis. Finally, we identify 15 critical aspects that provide a roadmap for the rational design of next-generation HEA catalysts for sustainable energy conversions and chemical transformations.

Oxidative stress in damaged or inflamed tissues presents a major barrier to the efficacy of cell-based therapies by impairing cell viability, function, and engraftment. Herein, we demonstrate a nanofiber-integrated three-dimensional spheroid platform that delivers Curcumin (Cur), a natural antioxidant, for cellular protection. Cur can be encapsulated in electrospun polycaprolactone (PCL) fibers, which are processed into short segments and coassembled with human mesenchymal stem cells to form spheroids. The integrated fibers enable a two-phase release profile of Cur while preserving spheroid morphology and maintaining cell organization. Under H2O2-induced oxidative stress, Cur-PCL-integrated spheroids showed improved cell viability and reduced mitochondrial reactive oxygen species compared with untreated controls. Unlike conventional nanoparticle-based systems that often rely on inefficient cellular uptake and can suffer from limited penetration in 3D aggregates, this fiber-segment approach provides a physically retained intraspheroidal depot that enables localized cytoprotection while preserving spheroid integrity, offering a scalable and injectable strategy for engineering resilient cell constructs. The system holds promise for improving the therapeutic performance of stem cell therapies in oxidative microenvironments associated with tissue injury and regeneration.

It remains a grand challenge to rationally design and synthesize nanocarriers with well-controlled surface properties to manipulate their interactions with cells and intracellular trafficking. Here, we report a rational synthesis of virus-mimicking nanocarriers characterized by a controlled number of hydrophobic protrusions on the hydrophilic surface. When a polystyrene bead is coated with a porogen-loaded SiO2 shell and then exposed to a good solvent, the polymer is swollen to generate an internal pressure against the shell. By adjusting the extent of porogen removal, the swollen polymer can push through the shell from one, two, or multiple sites to create up to 175 hydrophobic protrusions while leaving behind a cavity inside the shell. As the number of protrusions increases, polyvalent interactions with lipid bilayer are enabled and enhanced to promote both cellular uptake and endo/lysosomal escape. By leveraging the mesopores in the wall, the cavity can be readily loaded with various types of drugs for cytoplasmic delivery at maximal therapeutic efficacy. This work offers a rational approach to the development of advanced nanocarriers for biomedicine.

Metal nanocrystals in metastable phases have received increasing attention owing to their unique physicochemical properties and potential catalytic applications. Bulk Ru crystallizes in the hexagonal close-packed (hcp) phase, but colloidal methods have enabled the synthesis of Ru nanocrystals in the metastable face-centered cubic (fcc) phase. In this report, we highlight recent progress in engineering the phase of Ru nanocrystals, with a focus on methods based on the seed-templating effect, such as facet symmetry matching, and kinetic control over the reduction pathway. We also discuss the thermal stability of metastable fcc-Ru nanocrystals, as well as their catalytic applications. We further summarize how hcp-Ru nanocrystals can serve as templates to direct the synthesis of Pd and Rh nanocrystals in the metastable hcp phase. Finally, we offer perspectives on quantitative kinetic control, scalable synthesis, and stabilization of nanocrystals in metastable phases.

Noble-metal nanoframes are attractive for catalytic applications due to their open structures and large specific surface areas. However, traditional nanoframes are known to suffer from poor structural robustness because of their ultrathin ridges. Here, we address this issue by developing a new class of nanoframes characterized by relatively thick but hollow ridges. Our demonstration is based upon Pd and a typical synthesis involves the one-shot injection of PdBr2 powder suspension into an aqueous mixture containing Ag nanocubes, ascorbic acid, poly(vinyl pyrrolidone), and KBr held at 75 degrees C. The poor solubility of PdBr2 in water enables slow release of Pd(II) and thus a steady reduction rate for controlling the deposition of Pd atoms. During the synthesis, the side faces of Ag nanocubes are continuously carved away through galvanic replacement, accompanied by the deposition of Pd atoms on the corners and edges for the generation of cage cubes-cubes with through holes across the opposite faces. At a later stage, the Ag remaining in the ridges is etched away, leading to the formation of hollow ridges with a final composition of Pd1Ag2. The Pd-Ag alloy nanoframes exhibited good structural robustness during 1 h of chronoamperometric test toward formic acid oxidation reaction.

We report a facile synthesis of Au@Pd nanostructures with controllable porous shells by varying the concentration of KBr. Our mechanistic studies suggest that the porous morphology can be ascribed to an attachment growth process. Rapid reduction of Pd(II) precursor generates abundant Pd atoms in the initial stage of a synthesis. The Pd atoms self‐nucleate in the solution to generate a large number of ultrafine nanoparticles, which are subsequently deposited onto the surface of Au seeds through attachment growth. Increasing the concentration of KBr slows down the reduction kinetics, leading to the formation of fewer and larger Pd nanoparticles for the generation of less porous shells. A tensile lattice strain is identified in the Pd shell, providing more active catalytic sites. When evaluated as electrocatalysts toward formic acid oxidation, the porous Au@Pd nanocrystals exhibit a current density of 2.50 A mg−1, approximately six times greater than that of the commercial Pd/C, highlighting their great potential for applications in direct formic acid fuel cells.

We report a plasmonic platform based on Au nanospheres for the rapid detection and removal of trace Pd2+ and Pt2+ ions from aqueous systems. Upon exposure to Pd2+, Pt2+, or a mixture of them in the presence of a reductant, surface deposition occurs on the Au nanospheres, leading to pronounced damping of localized surface plasmon resonance that can be monitored by using ultraviolet-visible spectroscopy. By tuning the amount of Au nanospheres, the optical response can be optimized to achieve sensitive detection over a broad concentration range. Structural analyses reveal that the deposited Pd atoms are incorporated into the near-surface region of the nanospheres through interdiffusion, forming an alloyed layer rather than a sharp core-shell boundary. Because the plasmonic response is directly coupled to material uptake, this system enables simultaneous optical detection and removal of platinum-group metals (specifically, Pd2+ and Pt2+ in this work) from the solution.

A cell-based theranostic system can be fabricated by attaching nanomedicines to the surface of carrier cells, but it remains a challenge to achieve the attachment without involving endocytosis. Herein, we address this challenge by developing multifunctional Janus nanoparticles with orthogonal surface properties for the two opposite halves. When incubated with carrier cells, the hydrophobic half made of polystyrene readily inserts into the plasma membrane, whereas the hydrophilic SiO2 half grafted with poly(ethylene glycol) protrudes away from the cell surface. Additionally, the SiO2 half can be made with a cavity to hold theranostic agents and thus serves as a "backpack" for the carrier cell. By confining the theranostic agents in the SiO2 compartment and outside the carrier cell during the delivery process, their adverse impact on the cell is minimized. Upon release in an in vitro spheroid model, the agents quickly eradicate cancer cells. Moreover, the polystyrene half can be loaded with superparamagnetic nanoparticles to enhance magnetic resonance imaging contrast and enable magnetic manipulation, facilitating image-guided and target-directed treatments. By further optimizing the interactions between the multifunctional Janus nanoparticles and carrier cells, this system can be developed into a robust platform for cell-based theranostics.

Skin wound healing is a dynamic process, yet scaffolds enabling stage-specific modulation remain limited. We fabricated a nanofiber scaffold from FDA-approved materials, consisting of two outer layers of radially aligned and random poly(ε-caprolactone) fibers and a middle layer of electrosprayed phase-change microparticles loaded with platelet-derived growth factor-BB (PDGF-BB)/vascular endothelial growth factor (VEGF) in the periphery and PDGF-BB/epidermal growth factor (EGF) in the center. Near-infrared irradiation through a photomask enabled spatiotemporal control of growth factor release, aligning PDGF-BB, VEGF, and EGF delivery with specific phases of wound healing to promote vascularization, cell proliferation, and tissue remodeling. In a preclinical porcine model, it enhanced closure and modulated the microenvironment by activating PI3K-Akt, MAPK, and immune pathways, up-regulating genes for survival and repair while down-regulating those linked to apoptosis and inflammation. With scalable manufacturing and large-animal efficacy, this scaffold holds translational potential for skin wound healing.

Nonwoven mats of electrospun nanofibers are widely used in an array of applications, including those related to filtration, textiles, and tissue engineering. The performance of the mats is often plagued by their relatively weak mechanical strength due to the lack of bonding at the junction points between fibers. To address this issue, here a controllable technique is demonstrated for welding a nonwoven mat of poly(ε-caprolactone) fibers into an interconnected network by leveraging the photothermal effect of Au nanocages under the irradiation of a near-infrared laser. Upon irradiation for 2 s only, the poly(ε-caprolactone) fibers in a nonwoven mat are permanently welded at the junction points. When the irradiation time is increased to 5 s, the fibers fused together transforming the porous and opaque mat into a transparent solid film. In addition to strengthening nonwoven mats of electrospun nanofibers, this technique may open the door to new applications such as masking, patterning, and printing.

We report a versatile method based on seed-mediated growth for the facile synthesis of trimetallic Pd@PtxAu1−x core-shell nanocubes. By simply varying the feeding ratio between the Pt(II) and Au(III) precursors, the atomic ratio of Pt to Au in the shell and thereby the ensemble state of Pt atoms on the surface can be tuned to control the binding configuration of O2 molecules. Specifically, discrete Pt atoms on the surface promote the adsorption of O2 molecules in the Pauling configuration to enhance the catalytic selectivity of the nanoparticles toward H2O2 via the two-electron oxygen reduction reaction, with the Pd@Pt0.025Au0.975 nanocubes showing selectivity as high as 91% at 0.45 VRHE. This work offers a viable means to augment the electrocatalytic performance of alloy nanocrystals by controlling their surface compositions.

While the synthesis of Ag nanocubes has been extensively studied, sample preparation (including collection, washing, and redispersion) after the synthesis has received far less attention. Herein, we leverage the unique capability of surface-enhanced Raman scattering to investigate how the solvent used for sample preparation affects the surface chemistry of Ag nanocubes. Our findings reveal that the use of an appropriate solvent for sample preparation plays a vital role in preserving the cubic shape. Crushing the reaction mixture with acetone before centrifugation greatly improves collection efficiency by inducing reversible aggregation among the particles. It also promotes the coadsorption of the carbonyl group from acetone and Cl- ions on the Ag surface to suppress oxidative etching and thereby help preserve the cubic shape. Subsequent washing of the collected nanocubes with water or ethanol enables effective redispersion while facilitating the desorption of Cl- ions and the adsorption of the carbonyl group from poly(vinylpyrrolidone). Collectively, these results underscore the importance of processing conditions after a colloidal synthesis in preserving the desired properties of Ag nanocubes for an array of applications.

Despite remarkable progress, colloidal synthesis of metal nanocrystal is still far away from reaching the goal for robust, reproducible, and scalable production. Even with the adoption of seed-mediated growth, the synthesis can still be complicated by issues such as self-nucleation, galvanic replacement, stochastic symmetry reduction, and unwanted compositional variation. All these issues can be addressed by switching to steady-state synthesis characterized by a slow, constant, and tightly controlled reduction rate. Steady-state synthesis can be achieved by adding one reactant dropwise while using the other reactant in large excess, but this method is not suitable for scale-up production in a continuous flow reactor. There is a pressing need to develop alternative methods capable of establishing the steady-state kinetics characteristic of dropwise addition while introducing both reactants by one-shot injection. In this Perspective, we discuss a number of methods that allow for both one-shot injection and steady-state synthesis.

This study demonstrates that Au nanospheres are advantageous over their octahedral and cubic counterparts as seeds in the synthesis of Au@Pt core-shell nanocrystals with a monolayer shell. In combination with experimental characterization, we show through training a machine-learned interatomic potential that the Au nanospheres exhibit a large fraction of low-coordination atoms which are uniformly distributed over the surface. The corresponding high-index facets, including {211}, {311}, {331}, {210}, and {310}, on a spherical seed promote nucleation while greatly shortening the diffusion distance for adatoms. In addition, the high-index facets are instrumental in retaining the deposited Pt atoms on the outermost surface by retarding their inter-diffusional exchange with the underlying Au atoms. By switching from a monolayer made of pure Pt to those made of Pt-Au alloys, we can optimize both the activity and selectivity of the nanocrystals toward the two-electron oxygen reduction reaction for the electrochemical synthesis of H2O2. This method should be extendible to the fabrication of other core-shell nanocatalysts with desired monolayer shells for various catalytic reactions.

Noble-metal open nanostructures have remarkable catalytic capabilities toward a wide range of reactions. In particular, Pd-based open nanostructures have been synthesized and validated for superior catalytic performance toward formic acid oxidation. However, most of the syntheses are based on dropwise addition, making it challenging to increase the production volume. In this work, we present a facile approach to the synthesis of Ag@Pd core-frame nanocubes and then Pd-based nanoframes through one-shot injection. In a typical synthesis, Ag nanocubes are dispersed in an aqueous solution of ascorbic acid and polyvinylpyrrolidone at room temperature, followed by the injection of Pd(NH3)4(NO3)2 precursor in one shot. The Pd(NH3)4(NO3)2 precursor has a much slower reduction kinetics relative to Na2PdCl4, preventing self-nucleation and enabling controlled deposition of Pd atoms on the Ag nanocubes. The lower reduction potential of Pd(NH3)4(NO3)2 also helps minimize the galvanic replacement reaction, facilitating uniform deposition of Pd atoms. After selectively etching away the Ag template, Pd-based nanoframes with a rigid cubic structure are obtained. Finally, the synthesis is successfully adapted to a continuous flow system, generating Ag@Pd nanocubes with comparable quality to those obtained via one-shot synthesis, demonstrating a practical route to large-scale production of Pd-based nanoframes with H2O2 etching.

Significant advances in science and engineering often emerge at the intersections of disciplines. Nanoscience and nanotechnology are inherently interdisciplinary, uniting researchers from chemistry, physics, biology, medicine, materials science, and engineering. This convergence has fostered novel ways of thinking and enabled the development of materials, tools, and technologies that have transformed both basic and applied research, as well as how we address critical societal challenges. In this Nano Focus, we pose and explore 33 questions whose answers could profoundly impact fields such as energy, electronics, the environment, optics, and medicine. These questions highlight the need for deeper foundational understanding, improved tools and techniques, and innovative applications─each with significant societal relevance. Together, they represent a global call-to-action for the scientific community.