A biomimetic gradient porous cage with a micro-structure for enhancing mechanical properties and accelerating osseointegration in spinal fusion.

Objectives: Spinal fusion is a widely employed treatment of patients with degenerative disc disease, in which a cage is used to replace the disc for spinal fusion. But it often fails for insufficient mechanical strength and poor osseointegration. Here, we designed a polyether-ether-ketone (PEEK)/tantalum (Ta) composite cage with a biomimetic gradient porous micro-structure, simultaneously enhancing mechanical properties and accelerating osseointegration in spinal fusion. Materials and methods: In the study, based on the mechanical performances of PEEK and osteogenic potential of Ta, and the three-dimensional (3D) structures of cuttlebone and vertebra, the cages were respectively 3D printed by pure PEEK, PEEK with 5 wt% Ta (PEEK/Ta-5), PEEK with 10 wt% Ta (PEEK/Ta-10) and PEEK with 15 wt% Ta (PEEK/Ta-15), then verified in vitro and in sheep cervical fusion model systematically. Results: Vertebral Gyroid structure PEEK/Ta-15 cage exhibited superior mechanical properties than Cuttlebone-like structure PEEK/Ta-15 cage, closer to the cervical vertebra. Furthermore, PEEK/Ta-15 cage with higher Ta microparticles in PEEK provided a biomimetic gradient porous micro-structure with higher surface energy, guiding cell biological behavior, promoting new bone penetration, and accelerating osseointegration in vivo. Conclusion: In conclusion, the study designed a biomimetic gradient porous cage with a micro-structure for enhancing mechanical properties, accelerating osseointegration and forming an anatomical lock in the fusion segment through composites, mechanical efficiency, surface extension, and pores.

Manta Ray Inspired Soft Robot Fish with Tough Hydrogels as Structural Elements.

The design of soft robots capable of navigation underwater has received tremendous research interest due to the robots' versatile applications in marine explorations. Inspired by marine animals such as jellyfish, scientists have developed various soft robotic fishes by using elastomers as the major material. However, elastomers have a hydrophobic network without embedded water, which is different from the gel-state body of the prototypes and results in high contrast to the surrounding environment and thus poor acoustic stealth. Here, we demonstrate a manta ray-inspired soft robot fish with tailored swimming motions by using tough and stiff hydrogels as the structural elements, as well as a dielectric elastomer as the actuating unit. The switching between actuated and relaxed states of this unit under wired power leads to the flapping of the pectoral fins and swimming of the gel fish. This robot fish has good stability and swims with a fast speed (∼10 cm/s) in freshwater and seawater over a wide temperature range (4-50 °C). The high water content (i.e., ∼70 wt %) of the robot fish affords good optical and acoustic stealth properties under water. The excellent mechanical properties of the gels also enable easy integration of other functional units/systems with the robot fish. As proof-of-concept examples, a temperature sensing system and a soft gripper are assembled, allowing the robot fish to monitor the local temperature, raise warning signals by lighting, and grab and transport an object on demand. Such a robot fish should find applications in environmental detection and execution tasks under water. This work should also be informative for the design of other soft actuators and robots with tough hydrogels as the building blocks.

Digital Light Processing 3D Printing of Tough Supramolecular Hydrogels with Sophisticated Architectures as Impact-Absorption Elements.

Processing tough hydrogels into sophisticated architectures is crucial for their applications as structural elements. However, Digital Light Processing (DLP) printing of tough hydrogels is challenging because of the low-speed gelation and toughening process. Described here is a simple yet versatile system suitable for DLP printing to form tough hydrogel architectures. The aqueous precursor consists of commercial photoinitiator, acrylic acid, and zirconium ion (Zr4+ ), readily forming tough metallo-supramolecular hydrogel under digital light because of in situ formation of carboxyl-Zr4+ coordination complexes. The high-stiffness and antiswelling properties of as-printed gel enable high-efficiency printing to form high-fidelity constructs. Furthermore, swelling-induced morphing of the gel is also achieved by encoding structure gradients during the printing with grayscale digital light. Mechanical properties of the printed hydrogels are further improved after incubation in water due to the variation of local pH and rearrangement of coordination complex. The swelling-enhanced stiffness affords the printed hydrogel with shape fixation ability after manual deformations, and thereby provides an additional avenue to form more complex configurations. These printed hydrogels are used to devise an impact-absorption element or a high-sensitivity pressure sensor as proof-of-concept examples. This work should merit engineering of other tough gels and extend their scope of applications in diverse fields.

3D printing of a tough double-network hydrogel and its use as a scaffold to construct a tissue-like hydrogel composite.

To mimic biological tissues with high toughness such as cartilage, it is highly desired to fabricate stable and tough hydrogels with intricate shapes to act as a structural support. Extrusion-based 3D printing is a promising method to fabricate 3D scaffolds with various architectures; however, printing tough hydrogel structures with high fidelity and resolution is still a challenge. In this work, we adopt the fast sol-to-gel transition of κ-carrageenan in the solution of acrylamide upon cooling to fix the printed scaffolds and polymerize the precursor solution to form the second network. The printed constructs of κ-carrageenan/polyacrylamide double-network gels are toughened by soaking in an aqueous solution of zirconyl chloride to form coordination complexes between the Zr4+ ions and sulfate groups of κ-carrageenan. The obtained hydrogels are stable in water and possess good mechanical properties, with a tensile breaking stress of 1-2 MPa, breaking strain of 100-150%, and Young's modulus of 4-10 MPa. The printed grid can hold 150 times its own weight. 3D printed constructs with a high aspect ratio and shape fidelity are obtained by optimizing the printing parameters. Furthermore, a biomimetic strategy is applied to construct a hydrogel composite by filling the printed tough hydrogel scaffold with a cell-laden fibrin hydrogel as the soft substance. Chondrocytes in the hydrogel composite maintain high viability after cyclic compression, demonstrating the load-bearing capacity of the tough scaffold and favorable microenvironment for cells provided by the embedded soft fibrin gel. We envision that this printing strategy for hydrogel constructs with high toughness and good stability, as well as the method to form tough-soft hydrogel composites, can be extended to other systems to develop structural elements and scaffolds towards applications in biomedical devices and tissue engineering.

Engineering Tough Metallosupramolecular Hydrogel Films with Kirigami Structures for Compliant Soft Electronics.

A simple and effective approach is demonstrated to fabricate tough metallosupramolecular hydrogel films of poly(acrylic acid) by one-pot photopolymerization of the precursor solution in the presence of Zr4+ ions that form coordination complexes with the carboxyl groups and serve as the physical crosslinks of the matrix. Both as-prepared and equilibrated hydrogel films are transparent, tough, and stable over a wide range of temperature, ionic strength, and pH. The thickness of the films can be easily tailored with minimum value of ≈7 µm. Owing to the fast polymerization and gelation process, kirigami structures can be facilely encoded to the gel films by photolithographic polymerization, affording versatile functions such as additional stretchability and better compliance of the planar films to encapsulate objects with sophisticated geometries that are important for the design of soft electronics. By stencil printing of liquid metal on the hydrogel film with a kirigami structure, the integrated soft electronics shows good compliance to cover curved surfaces and high sensitivity to monitor human motions. Furthermore, this strategy is applied to diverse natural and synthetic macromolecules containing carboxyl groups to develop tough hydrogel films, which will open opportunities for the applications of hydrogel films in biomedical and engineering fields.

Reversibly Transforming a Highly Swollen Polyelectrolyte Hydrogel to an Extremely Tough One and its Application as a Tubular Grasper.

Poly(2-acrylamido-2-methyl-1-propanesulfonic acid) and its copolymer hydrogels are typical polyelectrolyte gels with extremely high swelling capacity that are widely used in industry. It's common to consider these hydrogels as weak materials that are difficult to toughen. Reported here is a facile strategy to transform swollen and weak poly(acrylamide-co-2-acrylamido-2-methyl-1-propanesulfonic acid) [P(AAm-co-AMPS)] hydrogels to tough ones by forming strong sulfonate-Zr4+ metal-coordination complexes. The resultant hydrogels with moderate water content possess high stiffness, strength, and fracture energy, which can be tuned over 3-4 orders of magnitude by controlling the composition and metal-to-ligand ratio. Owing to the dynamic nature of the coordination bonds, these hydrogels show rate- and temperature-dependent mechanical performances, as well as good self-recovery properties. This strategy is universal, as manifested by the drastically improved mechanical properties of hydrogels of various natural and synthetic sulfonate-containing polymers. The toughened hydrogels can be converted to the original swollen ones by breaking up the metal-coordination complexes in alkaline solutions. The reversible brittle-tough transition and concomitant dramatic volume change of polyelectrolyte hydrogels afford diverse applications, as demonstrated by the design of a tubular grasper with holding force a thousand times its own weight for objects with different geometries. It is envisioned that these hydrogels enable versatile applications in the biomedical and engineering fields.

[Evaluation and analysis of high-quality products of Liuwei Dihuang Pills].

Liuwei Dihuang Pills is a typical traditional Chinese medicine with "the same product made by many manufacturers". The quality and price of products made in various factories was different obviously. In this study, the quality differences of Liuwei Dihuang Pills were evaluated over multi-dimensions and throughout the whole production cycle involving raw materials, production process, quality control and post-marketing re-studies based on the "Chinese patent medicine evaluation standard with quality at the core" established earlier by our research group. The research results showed that the product quality of various manufacturers was significantly different, and the product quality was positively correlated with the market shares of enterprises, indicating that enterprises with more market shares paid more attention to product quality; and the sales determined the concern degree of enterprises on products, which was in line with general cognition. During the single-item evaluation of Liuwei Dihuang Pills, the score of raw material selection was relatively low, and the enterprises paid less attention to the initial raw materials. The whole production process was better, and the national compulsory implementation of "Production Quality Management Standard"(GMP) had a positive effect in improving product quality. Quality control could basically guarantee product quality. Intelligent manufacturing promoted by the government was beneficial to ensure product uniformity. The score rate of "quality evaluation" item was basically qualified, which indicated that the quality control level of Liuwei Dihuang Pills was acceptable as a whole, but there was still room for improvement. "Re-evaluation and Brand Construction" had the lowest scores, reflecting that enterprises did not pay enough attention to in-depth study and re-evaluation of "the same product made by many manufacturers". The evaluation results were in line with expectations, provided a reference example for the evaluation of high-quality Chinese patent medicine, a basis for the high-quality and good price of Chinese patent medicine, scientific data for improving medical insurance bidding, and thus facilitated promoting the healthy development of the traditional Chinese medicine industry.

[Research on evaluation criteria over quality as core index of high grade Chinese patent medicine].

"One drug was produced by many companies" is common in Chinese patent medicines. The quality and price of products from different manufacturers varies widely, and the efficacy is inconsistency. In order to ensure the quality of Chinese patent medicines and promote "Healthy national program" implementation, it is necessary to study the current status of Chinese patent medicines and carry out the evaluation criteria over quality as the core management of high grade Chinese patent medicines, which is set up to reflect the evaluation strategy and method of Chinese patent medicines from raw material, production, quality control, reevaluation and competitive power to the whole chain of brand construction. It aims to reveal the quality discrepancy from different manufacturers over the same Chinese patent medicines. The research and application will select a serials of high grade quality products, and provide reference basis for the scientific and reasonable price formation mechanism of Chinese patent medicines and purchasing drugs by centralized bidding, guide healthy competition in the market and promote the implementation of "healthy China 2030 program".

Ultrathin κ-Carrageenan/Chitosan Hydrogel Films with High Toughness and Antiadhesion Property.

Designing tough biopolymer-based hydrogels as structural biomaterials has both scientific and practical significances. We report a facile approach to prepare polysaccharide-based hydrogel films with remarkable mechanical performances and antiadhesion property. The hydrogel films with a thickness of 40-60 µm were prepared by mixing aqueous solutions of κ-carrageenan (κ-CG) and protonated chitosan (CS), evaporating the solvent, and then swelling the casted film in water to achieve the equilibrium state. The obtained κ-CG/CS gel films with a water content of 48-88 wt % possessed excellent mechanical properties with a breaking stress of 2-6.7 MPa and a breaking strain of 80-120%, superior to the most existing biopolymer-based hydrogels. The extraordinary mechanical properties of gel films obtained over a wide range of mass ratio of κ-CG to CS should be rooted in the synergistic effect of ionic and hydrogen bonds between the κ-CG and CS molecules. In addition, the tough gel films showed good self-recovery ability, biocompatibility, and cell antiadhesion property, making them promising as an artificial dura mater and diaphragm materials in the surgery. The design principle by incorporating multiple noncovalent bonds to toughen the biopolymer-based hydrogels should be applicable to other systems toward structural biomaterials with versatile properties.

[Discrimination of Lactarius and Russula Mushrooms with FTIR and Two-Dimensional Correlation Infrared Spectroscopy].

Tri-step infrared spectroscopy method of Fourier transform infrared spectroscopy, second derivative infrared spectroscopy and two-dimensional correlation infrared spectroscopy was firstly used to discriminate six species of mushrooms belonging to the genus Lactarius and Russula. The absorption bands of the original spectrum were very similar, which were composed by protein and polysaccharides, but tiny differences were observed at the position, shape and absorption intensities of peaks. Second derivative infrared spectroscopy technology was applied to study 6 species of the samples, there were obvious differences in the range of 1 800～1 400 and 1 200～800 cm-1. Two-dimensional correlation infrared spectroscopy can improve the resolution of spectra. Therefore two-dimensional correlation infrared spectroscopy was used to study 6 kinds of mushrooms. The results showed that there are three auto-peaks in the Lactarius, four in the Russula and significant differences in the number, intensity of auto-peaks and cross peaks were observed in the range of 1 690~1 420 cm-1. In addition, the peaks quantity, position, intensity of auto-peaks and cross peaks were different in the range of 1 110~920 cm-1. It demonstrates that tri-step infrared spectroscopy technology of Fourier transform infrared spectroscopy, second derivative infrared spectroscopy and two-dimensional correlation infrared spectroscopy is a rapid and effective method for discriminating Lactarius and Russula.

[Discrimination of Seven Species of Boletus with Fourier Transform Infrared Spectroscopy].

Fourier transform infrared spectroscopy, two-dimensional correlation infrared spectroscopy and principal component analysis were used to discriminate seven species of boletus belonging to the same genus. The results showed that the absorption bands of original spectra were similar, which were mainly composed of the absorption bands of protein and polysaccharides, but tiny differences were still observed at the position and intensities of peaks. Two-dimensional correlation infrared spectroscopy technology was applied to study the sample. It showed that there are 6 auto-peaks in the Boletus brunneissimus Chiu and Boletus bicolor, 5 auto-peaks in the Boletus speciosus, 4 auto-peaks in the Boletus griseus Forst and Boletus calopus, only 3 in the Boletus edulis and Boletus aereus in the range of 1 680~1 300 cm-1. The significant differences in the position, intensity of auto-peaks and cross peaks were still observed in the range of 1 680~1 300 cm-1. Same significant differences were observed in the range of 1 150~920 cm-1. Principal component analysis was conducted on boletus with second derivative infrared spectra in the range of 1 800~800 cm-1. All the samples were distinguished and the classification accuracy of principal component analysis is up to 100%. It is demonstrated that Fourier transform infrared spectroscopy combined with two-dimensional correlation infrared spectroscopy or principal component analysis is a rapid and effective method for discriminating mushrooms.