A Biostable l-DNA Hydrogel with Improved Stability for Biomedical Applications.

DNA hydrogels have attracted increasing attention owing to their excellent permeability and high mechanical strength, together with thixotropy, versatile programmability and good biocompatibility. However, the moderate biostability and immune stimulation of DNA have arisen as big concerns for future potential clinical applications. Herein, we report the self-assembly of a novel l-DNA hydrogel, which inherited the extraordinary physical properties of a d-DNA hydrogel. With the mirror-isomer deoxyribose, this hydrogel exhibited improved biostability, withstanding fetal bovine serum (FBS) for at least 1 month without evident decay of its mechanical properties. The low inflammatory response of the l-DNA hydrogel has been verified both in vitro and in vivo. Hence, this l-DNA hydrogel with outstanding biostability and biocompatibility can be anticipated to serve as an ideal 3D cell-culture matrix and implanted bio-scaffold for long-term biomedical applications.

Microrheology of DNA hydrogels.

A key objective in DNA-based material science is understanding and precisely controlling the mechanical properties of DNA hydrogels. We perform microrheology measurements using diffusing wave spectroscopy (DWS) to investigate the viscoelastic behavior of a hydrogel made of Y-shaped DNA (Y-DNA) nanostars over a wide range of frequencies and temperatures. We observe a clear liquid-to-gel transition across the melting temperature region for which the Y-DNA bind to each other. Our measurements reveal a cross-over between the elastic [Formula: see text] and loss modulus [Formula: see text] around the melting temperature [Formula: see text] of the DNA building blocks, which coincides with the systems percolation transition. This transition can be easily shifted in temperature by changing the DNA bond length between the Y shapes. Using bulk rheology as well, we further show that, by reducing the flexibility between the Y-DNA bonds, we can go from a semiflexible transient network to a more energy-driven hydrogel with higher elasticity while keeping the microstructure the same. This level of control in mechanical properties will facilitate the design of more sensitive molecular sensing tools and controlled release systems.

On the role of flexibility in linker-mediated DNA hydrogels.

Three-dimensional DNA networks, composed of tri- or higher valent nanostars with sticky, single-stranded DNA overhangs, have been previously studied in the context of designing thermally responsive, viscoelastic hydrogels. In this work, we use linker-mediated gels, where the sticky ends of two trivalent nanostars are connected through the complementary sticky ends of a linear DNA duplex. We can design this connection to be either rigid or flexible by introducing flexible, non-binding bases. The additional flexibility provided by these non-binding bases influences the effective elasticity of the percolating gel formed at low temperatures. Here we show that by choosing the right length of the linear duplex and non-binding flexible joints, we obtain a completely different phase behaviour to that observed for rigid linkers. In particular, we use dynamic light scattering as a microrheological tool to monitor the self-assembly of DNA nanostars with linear linkers as a function of temperature. While we observe classical gelation when using rigid linkers, the presence of flexible joints leads to a cluster fluid with a much-reduced viscosity. Using both the oxDNA model and a coarse-grained simulation to investigate the nanostar-linker topology, we hypothesise on the possible structure formed by the DNA clusters. Moreover, we present a systematic study of the strong viscosity increase of aqueous solutions in the presence of these DNA building blocks.

Self-Collapsing of Single Molecular Poly-Propylene Oxide (PPO) in a 3D DNA Network.

On the basis of DNA self-assembly, a thermal responsive polymer polypropylene oxide (PPO) is evenly inserted into a rigid 3D DNA network for the study of single molecular self-collapsing process. At low temperature, PPO is hydrophilic and dispersed uniformly in the network; when elevating temperature, PPO becomes hydrophobic but can only collapse on itself because of the fixation and separation of DNA rigid network. The process has been characterized by rheological test and Small Angle X-Ray Scattering test. It is also demonstrated that this self-collapsing process is reversible and it is believed that this strategy could provide a new tool to study the nucleation-growing process of block copolymers.

Supramolecular Hydrogels Based on DNA Self-Assembly.

Extracellular matrix (ECM) provides essential supports three dimensionally to the cells in living organs, including mechanical support and signal, nutrition, oxygen, and waste transportation. Thus, using hydrogels to mimic its function has attracted much attention in recent years, especially in tissue engineering, cell biology, and drug screening. However, a hydrogel system that can merit all parameters of the natural ECM is still a challenge. In the past decade, deoxyribonucleic acid (DNA) has arisen as an outstanding building material for the hydrogels, as it has unique properties compared to most synthetic or natural polymers, such as sequence designability, precise recognition, structural rigidity, and minimal toxicity. By simple attachment to polymers as a side chain, DNA has been widely used as cross-links in hydrogel preparation. The formed secondary structures could confer on the hydrogel designable responsiveness, such as response to temperature, pH, metal ions, proteins, DNA, RNA, and small signal molecules like ATP. Moreover, single or multiple DNA restriction enzyme sites could be incorporated into the hydrogels by sequence design and greatly expand the latitude of their responses. Compared with most supramolecular hydrogels, these DNA cross-linked hydrogels could be relatively strong and easily adjustable via sequence variation, but it is noteworthy that these hydrogels still have excellent thixotropic properties and could be easily injected through a needle. In addition, the quick formation of duplex has also enabled the multilayer three-dimensional injection printing of living cells with the hydrogel as matrix. When the matrix is built purely by DNA assembly structures, the hydrogel inherits all the previously described characteristics; however, the long persistence length of DNA structures excluded the small size meshes of the network and made the hydrogel permeable to nutrition for cell proliferation. This unique property greatly expands the cell viability in the three-dimensional matrix to several weeks and also provides an easy way to prepare interpenetrating double network materials. In this Account, we outline the stream of hydrogels based on DNA self-assembly and discuss the mechanism that brings outstanding properties to the materials. Unlike most reported hydrogel systems, the all-in-one character of the DNA hydrogel avoids the "cask effect" in the properties. We believe the hydrogel will greatly benefit cell behavior studies especially in the following aspects: (1) stem cell differentiation can be studied with solely tunable mechanical strength of the matrix; (2) the dynamic nature of the network can allow cell migration through the hydrogel, which will help to build a more realistic model to observe the migration of cancer cells in vivo; (3) combination with rapidly developing three-dimension printing technology, the hydrogel will boost the construction of three-dimensional tissues and artificial organs.

Tuning the Mechanical Properties of a DNA Hydrogel in Three Phases Based on ATP Aptamer.

By integrating ATP aptamer into the linker DNA, a novel DNA hydrogel was designed, with mechanical properties that could be tuned into three phases. Based on the unique interaction between ATP and its aptamer, the mechanical strength of the hydrogel increased from 204 Pa to 380 Pa after adding ATP. Furthermore, with the addition of the complementary sequence to the ATP aptamer, the mechanical strength could be increased to 570 Pa.

An intelligent method for identifying otological drill slippage.

An otological drill is a fundamental apparatus used for bone-milling in ear surgery. A common problem in bone-milling is that the drill bit slips on the bone surface. To improve the operational safety of such a surgery, this article presents a new apparatus combined with an intelligent method for identifying drill slippage. A two-axis force sensor is installed on a modified drill, and it detects the force of the bone's reaction to the drill bit. By integrating the unit reaction forces of the bone and the drill bit on the contact area, the functions of the force signals are deduced, which can reflect changes in the milling parameters. Based upon these functions, the slippage force, which is an important factor in drill slippage, is then extracted. An adaptive filter is specially designed to suppress interference in the slippage force. Drill slippage can be identified by calculating the variations in the filtering results. Five surgeons were invited to carry out an experiment in which they used this method on calvarian bones. Their average recognition rate of drill slippage was 86%, and only 1% of normal millings were identified as milling faults.

In Situ Formation of Covalent Second Network in a DNA Supramolecular Hydrogel and Its Application for 3D Cell Imaging.

DNA hydrogels have been demonstrated with important applications in three-dimensional cell culture in vitro due to their good biocompatibility, biodegradability, and permeability. In these applications, to observe the cell morphology and functions in situ, immobilization, labeling, and imaging processes are involved, which requires good stability of the hydrogels during washing and immersion. To improve the stability of the hydrogels for better imaging, here we built a covalent second network in a DNA supramolecular hydrogel by in situ polymerization and successfully constructed a stable three-dimensional transparent system for cell culture and observation. This strategy has been proved to be efficient in enhancing the mechanical properties and immobilizing the cells inside the hydrogel, which can be applied for immunostaining and cell imaging.

Precise pitch-scaling of carbon nanotube arrays within three-dimensional DNA nanotrenches.

Precise fabrication of semiconducting carbon nanotubes (CNTs) into densely aligned evenly spaced arrays is required for ultrascaled technology nodes. We report the precise scaling of inter-CNT pitch using a supramolecular assembly method called spatially hindered integration of nanotube electronics. Specifically, by using DNA brick crystal-based nanotrenches to align DNA-wrapped CNTs through DNA hybridization, we constructed parallel CNT arrays with a uniform pitch as small as 10.4 nanometers, at an angular deviation <2° and an assembly yield >95%.

Research on highly sensitive optomagnetic sensor for rapid detection of inflammation.

BACKGROUND: C-reactive protein (CRP) is used to evaluate the evolution of infections and sepsis in critically ill patients. For POCT testing, biosensor-based detection techniques offer quick and convenient application. OBJECTIVE: A prototype three dimensional chip was fabricated based on a new optomagnetic method to achieve the rapid detection of CRP. METHODS: This work investigates a new technology for the quick quantitative detection of the C-reactive protein (CRP) by total internal reflection magnetic imaging (TIRMI) on a three dimensional optomagnetic sensor. Transparent glass and hydrophilic plastic film with channels were used to construct the three dimensional sensor. The magnetic nanoparticles and immunological reagent were immobilized on the reaction area of the sensor. Samples were detected using total internal reflection magnetic spot imaging (TIRMI) based on a sandwich magnetic immunoassay by one-step assay. RESULTS: The developed 3D biosensor-TIRMI method showed a wide dynamic linear range (0.2-200 ng/ml) and quick detection (5 min) with low-sample volume (10 µL). CONCLUSIONS: We have presented a three dimensional optical protein chip that fulfills the demanding for point-of-care diagnostics in terms of ease-of-use (one step assay), miniaturization, assay time. This approach shows great promise for application in clinical investigations of biological samples.

Remote Controlling DNA Hydrogel by Magnetic Field.

DNA hydrogel has aroused widespread attention because of its unique properties. In this work, the DNA-modified magnetic nanoparticles were integrated into the mainframe of DNA hydrogel, resulting in DNA-MNP hydrogel. Under the magnetic field, this hydrogel can be remotely deformed into various shapes, driven to jump between two planes and even climb the hill. By applying various triggers, such as temperature, enzyme, and magnetic field, DNA-MNP hydrogel can specifically undergo sol-gel transition. This work not only imparts DNA hydrogel with a new fold of property but also opens a unique platform of such smart materials for its further applications.

Responsive Double Network Hydrogels of Interpenetrating DNA and CB[8] Host-Guest Supramolecular Systems.

A supramolecular double network hydrogel is presented by physical interpenetration of DNA and cucurbit[8]uril networks. In addition to exhibiting an increase in strength and thermal stability, the double network hydrogel possesses excellent properties such as stretchability, ductility, shear-thinning, and thixotropy. Moreover, it is enzymatically responsive to both nuclease and cellulase, as well as small molecules, showing great potential as a new soft material scaffold.

A method for identifying otological drill milling through bone tissue wall.

BACKGROUND: Otological drill milling through the bone tissue wall is a common milling fault in ear surgery. This paper presents a method for identifying milling faults and improving operation safety. METHODS: Force and current sensors are used. According to a DC motor model and a cutting force model, the features of the milling process were analysed and a dynamic model was established. The dynamic model could extract the characteristic curve of a milling fault and the phase difference between the current and force signals. An adaptive filter was designed to fuse the phase and amplitude of signals to suppress interference in the characteristic curve. According to the filtering result, milling states can be identified by a rule base. RESULTS: Five surgeons carried out experiments on calvarian bone. The average recognition rate of milling faults was 90%. Only 1% of normal millings were identified as milling faults. CONCLUSIONS: This method could be adapted to different surgeons and identify milling faults exactly.

A method for identifying otological drill entanglement with a cotton swab.

BACKGROUND: The entanglement of the otological drill with cotton swabs is a common milling fault in ear surgery. To improve operational safety, this paper presents a method for identifying this type of milling fault. METHODS: Force and current sensors were installed on a modified otological drill. In accordance with the DC motor model and cutting force model, two features of the milling process were extracted, namely the characteristic curve and the dynamic relationship between the sensor signals. These are complementary features. An adaptive filter was designed to fuse them together and output a curve that was sensitive to milling faults and was stable during normal milling. Based on the filtering data, a rule base is presented for identifying cotton swab entanglement. RESULTS: Five surgeons were invited to perform an experiment on calvarian bones. The average recognition rate for milling faults was 90%, whereas only 2% of normal millings were identified as milling faults. CONCLUSIONS: The presented method could adapt to the technique of different surgeons and identify milling faults exactly.

Automatic identification of otological drilling faults: an intelligent recognition algorithm.

BACKGROUND: This article presents an intelligent recognition algorithm that can recognize milling states of the otological drill by fusing multi-sensor information. METHODS: An otological drill was modified by the addition of sensors. The algorithm was designed according to features of the milling process and is composed of a characteristic curve, an adaptive filter and a rule base. The characteristic curve can weaken the impact of the unstable normal milling process and reserve the features of drilling faults. The adaptive filter is capable of suppressing interference in the characteristic curve by fusing multi-sensor information. The rule base can identify drilling faults through the filtering result data. RESULTS: The experiments were repeated on fresh porcine scapulas, including normal milling and two drilling faults. The algorithm has high rates of identification. CONCLUSIONS: This study shows that the intelligent recognition algorithm can identify drilling faults under interference conditions.

Automatic identification of otologic drilling faults: a preliminary report.

BACKGROUND: A preliminary study was carried out to identify parameters to characterize drilling faults when using an otologic drill under various operating conditions. METHODS: An otologic drill was modified by the addition of four sensors. Under consistent conditions, the drill was used to simulate three important types of drilling faults and the captured data were analysed to extract characteristic signals. A multisensor information fusion system was designed to fuse the signals and automatically identify the faults. RESULTS: When identifying drilling faults, there was a high degree of repeatability and regularity, with an average recognition rate of >70%. CONCLUSIONS: This study shows that the variables measured change in a fashion that allows the identification of particular drilling faults, and that it is feasible to use these data to provide rapid feedback for a control system. Further experiments are being undertaken to implement such a system.