2D material programming for 3D shaping.

Two-dimensional (2D) growth-induced 3D shaping enables shape-morphing materials for diverse applications. However, quantitative design of 2D growth for arbitrary 3D shapes remains challenging. Here we show a 2D material programming approach for 3D shaping, which prints hydrogel sheets encoded with spatially controlled in-plane growth (contraction) and transforms them to programmed 3D structures. We design 2D growth for target 3D shapes via conformal flattening. We introduce the concept of cone singularities to increase the accessible space of 3D shapes. For active shape selection, we encode shape-guiding modules in growth that direct shape morphing toward target shapes among isometric configurations. Our flexible 2D printing process enables the formation of multimaterial 3D structures. We demonstrate the ability to create 3D structures with a variety of morphologies, including automobiles, batoid fish, and real human face.

Injectable Click Chemistry-based Bioadhesives for Accelerated Wound Closure.

Tissue adhesives play a vital role in surgical processes as a substitute for sutures in wound closure. However, several existing tissue adhesives suffer from cell toxicity, weak tissue-adhesive strength, and high cost. In this study, by taking advantage of the fast and specific inverse-demand Diels-Alder cycloaddition reaction, a series of bioadhesives were produced by employing copper-free click chemistry pair trans-cyclooctene (TCO) /tetrazine (Tz) in chitosan. The gelation time of the bioadhesives can be optimized to be less than 2 minutes, which meets the need for surgical wound closure in practice. By adding 4-arm polyethylene glycol propionaldehyde (PEG-PALD) as a co-crosslinker, the adhesive strength of the bioadhesives was optimized to be 2.3 times higher than that of the conventional fibrin glue. Moreover, by adjusting the amount of the co-crosslinker, the swelling ratio and pore size of the chitosan bioadhesives can be tuned to fit the need of drug encapsulation and cell seeding. The chitosan bioadhesives possess no significant in vitro cytotoxicity. Using a mice skin incision wound model, we found that the chitosan bioadhesives were able to close the wound faster and promote wound healing process than the fibrin glue. In conclusion, our results support that the innovative click-chemistry based bioadhesives have been developed with improved physical and biological properties for surgical wound closures. STATEMENT OF SIGNIFICANCE: The manuscript describes a new group of click chemistry-based chitosan bioadhesives fabricated by reacting copper-free click chemistry pair trans-cyclooctene/tetrazine with co-crosslinker PEG-PALD. The new bioadhesives possess the properties of simple preparation, injectability, fast gelation, a minimal cytotoxicity, strong adhesive strength to tissue, and enhanced wound healing responses. This innovative strategy may draw interests of readers from the field of biomaterials, drug delivery, surgical device, and translational medicine.

Catalytic hydrogen atom transfer from hydrosilanes to vinylarenes for hydrosilylation and polymerization.

Because of the importance of hydrogen atom transfer (HAT) in biology and chemistry, there is increased interest in new strategies to perform HAT in a sustainable manner. Here, we describe a sustainable, net redox-neutral HAT process involving hydrosilanes and alkali metal Lewis base catalysts - eliminating the use of transition metal catalysts - and report an associated mechanism concerning Lewis base-catalysed, complexation-induced HAT (LBCI-HAT). The catalytic LBCI-HAT is capable of accessing both branch-specific hydrosilylation and polymerization of vinylarenes in a highly selective fashion, depending on the Lewis base catalyst used. In this process, earth abundant, alkali metal Lewis base catalyst plays a dual role. It first serves as a HAT initiator and subsequently functions as a silyl radical stabilizing group, which is critical to highly selective cross-radical coupling. EPR study identified a potassiated paramagnetic species and multistate density function theory revealed a high HAT character, yet multiconfigurational nature in the transition state of the reaction.

Umpolung α-Silylation of Cyclopropyl Acetates via Low-Temperature Catalytic C-C Activation.

We report a redox-neutral, catalytic C-C activation of cyclopropyl acetates to produce silicon-containing five-membered heterocycles in a highly region-and chemoselective fashion. The umpolung α-selective silylation leading to dioxasilolanes is opposed to contemporary ß-selective C-C functionalization protocols of cyclopropanols. Lewis base activation of dioxasilolanes as α-silyl carbinol equivalents undergoes the unconventional [1,2]-Brook rearrangement to form tertiary alcohols. Notably, mechanistic studies indicate that an electrophilic metal-π interaction harnessing highly fluorinated Tp (CF 3 ) 2 Rh(nbd) catalyst permitted a low-temperature C-C activation.

3D Printing of Anisotropic Hydrogels with Bioinspired Motion.

Motion in biological organisms often relies on the functional arrangement of anisotropic tissues that linearly expand and contract in response to external signals. However, a general approach that can implement such anisotropic behavior into synthetic soft materials and thereby produce complex motions seen in biological organisms remains a challenge. Here, a bioinspired approach is presented that uses temperature-responsive linear hydrogel actuators, analogous to biological linear contractile elements, as building blocks to create three-dimensional (3D) structures with programmed motions. This approach relies on a generalizable 3D printing method for building 3D structures of hydrogels using a fugitive carrier with shear-thinning properties. This study demonstrates that the metric incompatibility of an orthogonally growing bilayer structure induces a saddle-like shape change, which can be further exploited to produce various bioinspired motions from bending to twisting. The orthogonally growing bilayer structure undergoes a transition from a stretching-dominated motion to a bending-dominated motion during its shape transformation. The modular nature of this approach, together with the flexibility of additive manufacturing, enables the fabrication of multimodular 3D structures with complex motions through the assembly of multiple functional components, which in turn consist of simple linear contractile elements.

Bioinspired 3D structures with programmable morphologies and motions.

Living organisms use spatially controlled expansion and contraction of soft tissues to achieve complex three-dimensional (3D) morphologies and movements and thereby functions. However, replicating such features in man-made materials remains a challenge. Here we report an approach that encodes 2D hydrogels with spatially and temporally controlled growth (expansion and contraction) to create 3D structures with programmed morphologies and motions. This approach uses temperature-responsive hydrogels with locally programmable degrees and rates of swelling and shrinking. This method simultaneously prints multiple 3D structures with custom design from a single precursor in a one-step process within 60 s. We suggest simple yet versatile design rules for creating complex 3D structures and a theoretical model for predicting their motions. We reveal that the spatially nonuniform rates of swelling and shrinking of growth-induced 3D structures determine their dynamic shape changes. We demonstrate shape-morphing 3D structures with diverse morphologies, including bioinspired structures with programmed sequential motions.

Single-walled carbon nanotubes as near-infrared optical biosensors for life sciences and biomedicine.

Single-walled carbon nanotubes that emit photostable near-infrared fluorescence have emerged as near-infrared optical biosensors for life sciences and biomedicine. Since the discovery of their near-infrared fluorescence, researchers have engineered single-walled carbon nanotubes to function as an optical biosensor that selectively modulates its fluorescence upon binding of target molecules. Here we review the recent advances in the single-walled carbon nanotube-based optical sensing technology for life sciences and biomedicine. We discuss the structure and optical properties of single-walled carbon nanotubes, the mechanisms for molecular recognition and signal transduction in single-walled carbon nanotube complexes, and the recent development of various single-walled carbon nanotube-based optical biosensors. We also discuss the opportunities and challenges to translate this emerging technology into biomedical research and clinical use, including the biological safety of single-walled carbon nanotubes. The advances in single-walled carbon nanotube-based near-infrared optical sensing technology open up a new avenue for in vitro and in vivo biosensing with high sensitivity and high spatial resolution, beneficial for many areas of life sciences and biomedicine.

Physiologically relevant organs on chips.

Recent advances in integrating microengineering and tissue engineering have generated promising microengineered physiological models for experimental medicine and pharmaceutical research. Here we review the recent development of microengineered physiological systems, or also known as "ogans-on-chips", that reconstitute the physiologically critical features of specific human tissues and organs and their interactions. This technology uses microengineering approaches to construct organ-specific microenvironments, reconstituting tissue structures, tissue-tissue interactions and interfaces, and dynamic mechanical and biochemical stimuli found in specific organs, to direct cells to assemble into functional tissues. We first discuss microengineering approaches to reproduce the key elements of physiologically important, dynamic mechanical microenvironments, biochemical microenvironments, and microarchitectures of specific tissues and organs in microfluidic cell culture systems. This is followed by examples of microengineered individual organ models that incorporate the key elements of physiological microenvironments into single microfluidic cell culture systems to reproduce organ-level functions. Finally, microengineered multiple organ systems that simulate multiple organ interactions to better represent human physiology, including human responses to drugs, is covered in this review. This emerging organs-on-chips technology has the potential to become an alternative to 2D and 3D cell culture and animal models for experimental medicine, human disease modeling, drug development, and toxicology.

Molecular recognition using corona phase complexes made of synthetic polymers adsorbed on carbon nanotubes.

Understanding molecular recognition is of fundamental importance in applications such as therapeutics, chemical catalysis and sensor design. The most common recognition motifs involve biological macromolecules such as antibodies and aptamers. The key to biorecognition consists of a unique three-dimensional structure formed by a folded and constrained bioheteropolymer that creates a binding pocket, or an interface, able to recognize a specific molecule. Here, we show that synthetic heteropolymers, once constrained onto a single-walled carbon nanotube by chemical adsorption, also form a new corona phase that exhibits highly selective recognition for specific molecules. To prove the generality of this phenomenon, we report three examples of heteropolymer-nanotube recognition complexes for riboflavin, L-thyroxine and oestradiol. In each case, the recognition was predicted using a two-dimensional thermodynamic model of surface interactions in which the dissociation constants can be tuned by perturbing the chemical structure of the heteropolymer. Moreover, these complexes can be used as new types of spatiotemporal sensors based on modulation of the carbon nanotube photoemission in the near-infrared, as we show by tracking riboflavin diffusion in murine macrophages.

Single-walled carbon nanotube-based near-infrared optical glucose sensors toward in vivo continuous glucose monitoring.

This article reviews research efforts on developing single-walled carbon nanotube (SWNT)-based near-infrared (NIR) optical glucose sensors toward long-term in vivo continuous glucose monitoring (CGM). We first discuss the unique optical properties of SWNTs and compare SWNTs with traditional organic and nanoparticle fluorophores regarding in vivo glucose-sensing applications. We then present our development of SWNT-based glucose sensors that use glucose-binding proteins and boronic acids as a high-affinity molecular receptor for glucose and transduce binding events on the receptors to modulate SWNT fluorescence. Finally, we discuss opportunities and challenges in translating the emerging technology of SWNT-based NIR optical glucose sensors into in vivo CGM for practical clinical use.

A structure-function relationship for the optical modulation of phenyl boronic acid-grafted, polyethylene glycol-wrapped single-walled carbon nanotubes.

Phenyl boronic acids (PBA) are important binding ligands to pendant diols useful for saccharide recognition. The aromatic ring can also function to anchor an otherwise hydrophilic polymer backbone to the surface of hydrophobic graphene or carbon nanotube. In this work, we demonstrate both functions using a homologous series of seven phenyl boronic acids conjugated to a polyethylene glycol, eight-membered, branched polymer (PPEG8) that allows aqueous dispersion of single-walled carbon nanotubes (SWNT) and quenching of the near-infrared fluorescence in response to saccharide binding. We compare the 2-carboxyphenylboronic acid (2CPBA); 3-carboxy- (3CPBA) and 4-carboxy- (4CPBA) phenylboronic acids; N-(4-phenylboronic)succinamic acid (4SCPBA); 5-bromo-3-carboxy- (5B3CPBA), 3-carboxy-5-fluoro- (5F3CPBA), and 3-carboxy-5-nitro- (5N3CPBA) phenylboronic acids, demonstrating a clear link between SWNT photoluminescence quantum yield and boronic acid structure. Surprisingly, quantum yield decreases systematically with both the location of the BA functionality and the inclusion of electron-withdrawing or -donating substituents on the phenyl ring. For three structural isomers (2CPBA, 3CPBA, and 4CPBA), the highest quantum yields were measured for para-substituted PBA (4CPBA), much higher than ortho- (2CPBA) and meta- (3CPBA) substituted PBA, indicating the first such dependence on molecular structure. Electron-withdrawing substituents such as nitro groups on the phenyl ring cause higher quantum yield, while electron-donating groups such as amides and alkyl groups cause a decrease. The solvatochromic shift of up to 10.3 meV was used for each case to estimate polymer surface coverage on an areal basis using a linear dielectric model. Saccharide recognition using the nIR photoluminescence of SWNT is demonstrated, including selectivity toward pentoses such as arabinose, ribose, and xylose to the exclusion of the expected fructose, which has a high selectivity on PBA due to the formation of a tridentate complex between fructose and PBA. This study is the first to conclusively link molecular structure of an adsorbed phase to SWNT optical properties and modulation in a systematic manner.

Structure and function of glucose binding protein-single walled carbon nanotube complexes.

Understanding the structure and function of glucose binding proteins (GBP) complexed with single walled carbon nanotubes (SWNTs) is important for the development of applications including fluorescent sensors and nanostructure particle tracking. Herein, circular dichroism (CD), thermal denaturation, photo-absorption spectroscopy and atomic force microscopy are used to study these nanostructures. The protein retains its glucose-binding activity after complexation and is thermally stable below 36 °C. However, the SWNT lowers the midpoint denaturation temperature (Tm) by 5 °C and 4 °C in the absence and presence of 10 mM glucose, respectively. This data highlights that using techniques such as CD and thermal denaturation may be necessary to fully characterize such protein-nanomaterial nanostructures.

Boronic acid library for selective, reversible near-infrared fluorescence quenching of surfactant suspended single-walled carbon nanotubes in response to glucose.

We describe the high-throughput screening of a library of 30 boronic acid derivatives to form complexes with sodium cholate suspended single-walled carbon nanotubes (SWNTs) to screen for their ability to reversibly report glucose binding via a change in SWNT fluorescence. The screening identifies 4-cyanophenylboronic acid which uniquely causes a reversible wavelength red shift in SWNT emission. The results also identify 4-chlorophenylboronic acid which demonstrates a turn-on fluorescence response when complexed with SWNTs upon glucose binding in the physiological range of glucose concentration. The mechanism of fluorescence modulation in both of these cases is revealed to be a photoinduced excited-state electron transfer that can be disrupted by boronate ion formation upon glucose binding. The results allow for the elucidation of design rules for such sensors, as we find that glucose recognition and transduction is enabled by para-substituted, electron-withdrawing phenyl boronic acids that are sufficiently hydrophobic to adsorb to the nanotube surface.

Biofunctionalized nanoneedles for the direct and site-selective delivery of probes into living cells.

BACKGROUND: Accessing the interior of live cells with minimal intrusiveness for visualizing, probing, and interrogating biological processes has been the ultimate goal of much of the biological experimental development. SCOPE OF REVIEW: The recent development and use of the biofunctionalized nanoneedles for local and spatially controlled intracellular delivery brings in exciting new opportunities in accessing the interior of living cells. Here we review the technical aspect of this relatively new intracellular delivery method and the related demonstrations and studies and provide our perspectives on the potential wide applications of this new nanotechnology-based tool in the biological field, especially on its use for high-resolution studies of biological processes in living cells. MAJOR CONCLUSIONS: Different from the traditional micropipette-based needles for intracellular injection, a nanoneedle deploys a sub-100-nm-diameter solid nanowire as a needle to penetrate a cell membrane and to transfer and deliver the biological cargo conjugated onto its surface to the target regions inside a cell. Although the traditional micropipette-based needles can be more efficient in delivery biological cargoes, a nanoneedle-based delivery system offers an efficient introduction of biomolecules into living cells with high spatiotemporal resolution but minimal intrusion and damage. It offers a potential solution to quantitatively address biological processes at the nanoscale. GENERAL SIGNIFICANCE: The nanoneedle-based cell delivery system provides new possibilities for efficient, specific, and precise introduction of biomolecules into living cells for high-resolution studies of biological processes, and it has potential application in addressing broad biological questions. This article is part of a Special Issue entitled Nanotechnologies - Emerging Applications in Biomedicine.

Nanoneedle: a multifunctional tool for biological studies in living cells.

Studying biology in living cells is methodologically challenging but highly beneficial. Recent advances in nanobiotechnology offer exciting new opportunities to address this challenge. The nanoneedle technology, as an emerging technology that uses a cell membrane-penetrating nanoneedle to probe and manipulate biological processes in living cells, is expected to play an important role in this endeavor. Here we review the recent development and future direction of the nanoneedle technology for biological studies in living cells. The nanoneedle technology is shown to be powerful and versatile, and can offer numerous new ways to explore biological processes and biophysical properties of living cells with high spatial and temporal precision potentially reaching molecular resolution.

Mechanochemical delivery and dynamic tracking of fluorescent quantum dots in the cytoplasm and nucleus of living cells.

Studying molecular dynamics inside living cells is a major but highly rewarding challenge in cell biology. We present a nanoscale mechanochemical method to deliver fluorescent quantum dots (QDs) into living cells, using a membrane-penetrating nanoneedle. We demonstrate the selective delivery of monodispersed QDs into the cytoplasm and the nucleus of living cells and the tracking of the delivered QDs inside the cells. The ability to deliver and track QDs may invite unconventional strategies for studying biological processes and biophysical properties in living cells with spatial and temporal precision, potentially with molecular resolution.

Voltage generation from individual BaTiO(3) nanowires under periodic tensile mechanical load.

Direct tensile mechanical loading of an individual single-crystal BaTiO(3) nanowire was realized to reveal the direct piezoelectric effect in the nanowire. Periodic voltage generation from the nanowire was produced by a periodically varying tensile mechanical strain applied with a precision mechanical testing stage. The measured voltage generation from the nanowire was found to be directly proportional to the applied strain rate and was successfully modeled through the consideration of an equivalent circuit for a piezoelectric nanowire under low-frequency operation. The study, besides demonstrating a controlled experimental method for the study of direct piezoelectric effect in nanostructures, implies also the use of such perovskite piezoelectric nanowires for efficient energy-harvesting applications.

Individual nanotube-based needle nanoprobes for electrochemical studies in picoliter microenvironments.

We report the fabrication and characterization of individual nanotube-based, long and straight needle nanoprobes for electrochemistry and the study of their applicability and behavior in microenvironments. The needle nanoprobe, with a nanoscale ring-shaped Au electrode at the tip of the needle serving as the active electrode, was characterized by electrochemical current measurement and cyclic voltammetry and analyzed with electrochemical models. Such a needle nanoprobe, in combination with another metal-coated nanowire as a reference electrode, was further used, for the first time, for local electrochemical sensing inside microdroplets having volumes down to a few picoliters. We explain the acquired voltammetric behaviors of redox-active molecules in confined microscale environments and reveal a unique electrochemical mechanism which allows the regeneration of the redox-active molecules and the establishment of a stable reference potential in the microenvironments.