Control of blood capillary networks and holes in blood-brain barrier models by regulating elastic modulus of scaffolds.

The blood-brain barrier (BBB) is a type of capillary network characterized by a highly selective barrier, which restricts the transport of substances between the blood and nervous system. Numerous in vitro models of the BBB have been developed for drug testing, but a BBB model with controllable capillary structures remains a major challenge. In this study, we report for the first time a unique method of controlling the blood capillary networks and characteristic holes formation in a BBB model by varying the elastic modulus of a three-dimensional scaffold. The characteristic hole structures are formed by the migration of endothelial cells from the model surface to the interior, which have functions of connecting the model interior to the external environment. The hole depth increased, as the elastic modulus of the fibrin gel scaffold increased, and the internal capillary network length increased with decreasing elastic modulus. Besides, internal astrocytes and pericytes were also found to be important for inducing hole formation from the model surface. Furthermore, RNA sequencing indicated up-regulated genes related to matrix metalloproteinases and angiogenesis, suggesting a relationship between enzymatic degradation of the scaffolds and hole formation. The findings of this study introduce a new method of fabricating complex BBB models for drug assessment.

3D puzzle-inspired construction of large and complex organ structures for tissue engineering.

3D printing as a powerful technology enables the fabrication of organ structures with a programmed geometry, but it is usually difficult to produce large-size tissues due to the limited working space of the 3D printer and the instability of bath or ink materials during long printing sessions. Moreover, most printing only allows preparation with a single ink, while a real organ generally consists of multiple materials. Inspired by the 3D puzzle toy, we developed a "building block-based printing" strategy, through which the preparation of 3D tissues can be realized by assembling 3D-printed "small and simple" bio-blocks into "large and complex" bioproducts. The structures that are difficult to print by conventional 3D printing such as a picture puzzle consisting of different materials and colors, a collagen "soccer" with a hollow yet closed structure, and even a full-size human heart model are successfully prepared. The 3D puzzle-inspired preparation strategy also allows for a reasonable combination of various cells in a specified order, facilitating investigation into the interaction between different kinds of cells. This strategy opens an alternative path for preparing organ structures with multiple materials, large size and complex geometry for tissue engineering applications.

3D Printing of Collagen Scaffold with Enhanced Resolution in a Citrate-Modulated Gellan Gum Microgel Bath.

3D printing in a microgel-based supporting bath enables the construction of complex structures with soft and watery biomaterials but the low print resolution is usually an obstacle to its practical application in tissue engineering. Herein, high-resolution printing of a 3D collagen organ scaffold is realized by using an engineered Gellan gum (GG) microgel bath containing trisodium citrate (TSC). The introduction of TSC into the bath system not only mitigates the aggregation of GG microgels, leading to a more homogeneous bath morphology but also suppresses the diffusion of the collagen ink in the bath due to the dehydration effect of TSC, both of which contribute to the improvement of print resolution. 3D collagen organ structures such as hand, ear, and heart are successfully constructed with high shape fidelity in the developed bath. After printing, the GG and TSC can be easily removed by washing with water, and the obtained collagen product exhibits good cell affinity in a tissue scaffold application. This work offers an easy-to-operate strategy for developing a microgel bath for high-resolution printing of collagen, providing an alternative path to in vitro 3D organ construction.

Comparative analysis of the residues of granular support bath materials on printed structures in embedded extrusion printing.

Embedded extrusion printing facilitates the fabrication of complex biological structures using soft hydrogels that are challenging to construct using conventional manufacturing methods. While this targeting strategy is appealing, the residues of support materials on the printed objects have been overlooked. Here, we quantitatively compare the bath residues on fibrin gel fibers printed in granular gel baths that are conjugated with fluorescent probes for visualization, including physically crosslinked gellan gum (GG) and gelatin (GEL) baths and chemically crosslinked polyvinyl alcohol baths. Notably, all support materials can be detected on a microscopic scale, even on structures without any visible residues. Quantitative results indicate that baths with smaller size or lower shear viscosity show more and deeper diffusion into the extruded inks, and the removal efficiency of support materials depends mainly on the dissolving property of the granular gel baths. The residual amount of chemically cross-linked support materials on fibrin gel fibers is 28-70µg mm-2, which is tens of times higher than physically cross-linked GG (7.5µg mm-2) and GEL (0.3µg mm-2) baths. Meanwhile, cross-sectional images suggest that most gel particles are distributed around the fiber surface, but a small amount is in the fiber center. Such bath residues or the blank pores created by the removal of gel particles induce changes in product surface morphology, physicochemical and mechanical properties, impeding cell adhesion. This study will draw attention to the effects of residual support materials on printed structures and encourage the development of new strategies to diminish these residues or to take advantage of the residual support baths to improve product performances.

Self-healing bottlebrush polymer networks enabled via a side-chain interlocking design.

Exploring novel healing mechanisms is a constant impetus for the development of self-healing materials. Herein, we find that side-chain interlocking of bottlebrush polymers can form a dynamic network and thereby serve as a driving force for the self-healing process of the materials. Molecular dynamics simulation indicates that the interlocking is formed by the interpenetration between the long side chains of adjacent molecules and stabilized by van der Waals interactions and molecular entanglements of side chains. The interlocking can be tailored by changing the length and density of the side chains through atom transfer radical polymerization. As a result, the optimized bottlebrush polymer shows a healing efficiency of up to 100%. Unlike chemical interactions, side-chain interlocking eliminates the introduction of specific chemical groups. Therefore, bottlebrush polymers can even self-heal under harsh aqueous conditions, including acid and alkali solutions. Moreover, the highly dynamic side-chain interlocking enables bottlebrush polymers to efficiently dissipate vibration energy, and thus they can be used as damping materials. Collectively, side-chain interlocking expands the scope of physical interactions in self-healing materials and hews out a versatile way for polymers to accomplish self-healing capability in various environments.

"Out-of-the-box" Granular Gel Bath Based on Cationic Polyvinyl Alcohol Microgels for Embedded Extrusion Printing.

Embedded extrusion printing provides a versatile platform for fabricating complex hydrogel-based biological structures with living cells. However, the time-consuming process and rigorous storage conditions of current support baths hinder their commercial application. This work reports a novel "out-of-the-box" granular support bath based on chemically crosslinked cationic polyvinyl alcohol (PVA) microgels, which is ready to use by simply dispersing the lyophilized bath in water. Notably, with ionic modification, PVA microgels yield reduced particle size, uniform distribution, and appropriate rheological properties, contributing to high-resolution printing. Following by the lyophilization and re-dispersion process, ion-modified PVA baths recover to its original state, with unchanged particle size, rheological properties, and printing resolution, demonstrating its stability and recoverability. Lyophilization facilitates the long-term storage and delivery of granular gel baths, and enables the application of "out-of-the-box" support materials, which will greatly simplify experimental procedures, avoid labor-intensive and time-consuming operations, thus accelerating the broad commercial development of embedded bioprinting.

Resolution of 3D bioprinting inside bulk gel and granular gel baths.

Three-dimensional (3D) bioprinting has rapidly developed in the last decade, playing an increasingly important role in applications including pharmacokinetics research, tissue engineering, and organ regeneration. As a cutting-edge technology in 3D printing, gel bath-supported 3D bioprinting enables the freeform construction of complex structures with soft and water-containing materials, facilitating the in vitro fabrication of live tissue or organ models. To realize in vivo-like organs or tissues in terms of biological functions and complex structures by 3D printing, high resolution and fidelity are prerequisites. Although a wide range of gel matrices have recently been developed as supporting materials, the effect of bath properties and printing parameters on the print resolution is still not clearly understood. This review systematically introduces the decisive factors for resolution in both bulk gel bath systems and granular microgel bath systems, providing guidelines for high-resolution 3D bioprinting based on bath properties and printing parameters.

Superfast flow reactor derived from the used cigarette filter for the degradation of pollutants in water.

Developing high value-added products from the waste materials is highly promising from the perspective of environmental protection and resource recovery. Herein, the used cigarette filter was recycled to prepare the flow reactor via a clean and facile strategy. A continuous-flow reduction method was adopted to produce the gold nanoparticles on deacetylated cigarette filter without any extra chemical modifier, reductant or surfactant. The obtained filter was applied as a continuous-flow reactor and showed a high permeability and ultrafast flow catalytic ability. The permeability coefficient of the reactor was about 1.4 × 10-10 m2. This work provided a clean method to covert the waste cigarette filter to useful flow reactor with the relatively simple steps, and the product had a potential for the fast reduction of 4-nitrophenol and dyes including methyl blue and methylene orange.

Dual roles of cellulose monolith in the continuous-flow generation and support of gold nanoparticles for green catalyst.

Monolithic flow reactors are widely applied in numerous reactions due to its high efficiency and good reusability, but the green and efficient fabrication of monolithic flow catalytic system is still a challenge. Herein, the cellulose monolith prepared using a facile temperature-induced phase separation method was utilized to generate and immobilize the gold nanoparticles by a continuous-flow strategy, in which the cellulose monolith served as both reducing agent and supporting material. This process was conducted at room temperature and avoided the tedious surface modification of cellulose. The obtained cellulose-Au monolith can be directly applied as a green flow reactor in both water and organic solvents, and exhibited superior catalytic efficiency and good stability. This work provides a highly efficient, scalable and sustainable strategy for developing green catalytic system based on environmentally friendly cellulose monolith materials.

Monolithic cellulose supported metal nanoparticles as green flow reactor with high catalytic efficiency.

A highly effective, stable and reusable flow microreactor was developed by utilizing the environmentally sustainable porous monolithic cellulose based on a facile temperature induced phase separation (TIPS) method. The obtained microreator could be applied to efficiently and continuously catalysing the reduction reaction of 4-nitrophenol (an important reaction in water treatment) without any post-treatment or regeneration of catalysts. Moreover, the monolith overcame the brittleness of the crystalline cellulose and showed a good mechanical resilience, suggesting a great potential for the practical application in severe environment. Compared with previous reported Pd supported catalytic systems, this microreactor exhibited extremely high catalytic efficiency (turnover frequency, TOF = 4660 h-1, almost 4 times higher than that of cellulose nanocrystals supported catalyst) and long-term stability. This work provided a new strategy to construct highly effective and reusable metal NPs involved catalytic system by utilizing biodegradable cellulose materials.

Synergistic effect of CB and GO/CNT hybrid fillers on the mechanical properties and fatigue behavior of NR composites.

In this paper, graphene oxide (GO) and carbon nanotube (CNT) hybrid fillers were used to replace partial carbon black (CB), and GO/CNT/CB/NR composites were prepared with excellent crack growth resistance, low heat build-up and superior mechanical properties. Mechanical testing revealed a significant synergistic reinforcement between GO/CNT and CB in NR composites. The improved dispersion of GO/CNT hybrid fillers and CB in the NR matrix was characterized by transmission electron microscopy (TEM). Through the fatigue test, the GO/CNT/CB/NR composites showed excellent fatigue crack growth resistance and low heat build-up compared to CB/NR composites. These properties provide the NR composites with better applications in industry.