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microRNAs (miRNAs), a kind of small noncoding RNAs, are considered able to regulate expression of genes and mediate RNA silencing. miR-129-5p was shown to be a cancer-related miRNA. However, the influence of miR-129-5p in rectal adenocarcinoma (READ) development remains to be determined. Based on the TCGA data, downregulation of miR-129-5p in READ samples was observed. Manual restoration of the miR-129-5p in SW1463 and SW480 cell lines significantly inhibited invasion, migration, and proliferation of READ cell lines, while the apoptosis ability was enhanced. Meanwhile, we found E2F7 acted as a potential target of miR-129-5p and was upregulated in READ samples. E2F7 upregulation reversed the repression of miR-129-5p on READ development. Finally, in vivo experiments showed that inhibition of tumor growth in nude mice was achieved through upregulating miR-129-5p. Overall, our findings suggest increasing of miR-129-5p leads to the suppression of READ progression through regulating the expression of E2F7, which may provide novel insights into the treatment of READ.

Biocomposite systems evolve to superior structural strategies in adapting to their living environments, using limited materials to form functionality superior to their inherent properties. The synergy of physical-field and 3D printing technologies creates unprecedented opportunities that overcome the limitations of traditional manufacturing methods and enable the precise replication of bio-enhanced structures. Here, we provide an overview of typical structural designs in biocomposite systems, their functions and properties, and highlight the recent advances in bio-inspired composites using mechanical, electrical, magnetic, and ultrasound -field-assisted 3D printing techniques. Finally, in order to realize the preparation of bionic functional devices and equipment with more superior functions, we here provide an outlook on the development of field-assisted 3D printing technology from three aspects: materials, technology and post-processing. This article is protected by copyright. All rights reserved.

For prey, seeding, and protection, plants exhibit ingenious adaptive motions that respond autonomously to environmental stimuli by varying cellular organization, anisotropic orientation of cellulose fibers, mechanical instability design, etc. Notably, plants do not leverage muscle and nerves to produce and regulate their motions. In contrast, they harvest energy from the ambient environment and compute through embodied intelligence. These characteristics make them ideal candidates for application in self-morphing devices. Four-dimensional (4D) printing is a bottom-up additive manufacturing method that builds objects with the ability to change shape/properties in a predetermined manner. A versatile motion design catalog is required to predict the morphing processes and final states of the printed parts. This review summarizes the morphing and actuation mechanisms of plants and concludes with the recent development of 4D-printed smart materials inspired by the locomotion and structures of plant systems. We provide analyses of the challenges and our visions of biomimetic 4D printing, hoping to boost its application in soft robotics, smart medical devices, smart parts in aerospace, etc.

The self-morphing mechanism of some plant organs had inspired researchers to facilitate the realization of smart composites, and 3-D printing had shown its superiority in this area. However, composites fabricated directly by the 3-D printer are too soft, and complexity of the ink preparation is still very high. In this study, we presented a new method which combined 3-D printing technique and impregnation process to develop the biomimetic fibre-reinforced composites with programmable self-morphing properties. The new composites are reinforced by the continuous fibers which can effectively increase their mechanical property like cellulose fibrils in plant tissue. Moreover, matrices of the composites are made by the commercial water swelling rubbers, thus extend the choice of the compatible materials and reduce their preparation cost. Finally, the flexible method helps the smart composites to undergo specific shape transformations, like bending, twisting, and other inhomogeneous deformation.

Shape memory polymers (SMPs) generally change shape from a temporary state to a permanent state, and the permanent shape is only determined by its initial form, which leads to the lack of design freedom for SMPs. In order to enrich morphing behavior and extend applications of SMPs, bioinspired design and fabrication methods need to be developed. Many biological dynamic materials enable shape changes ranging from bending, twisting to spiraling using site-specific aligned cellulose microfibers orientations. Here, we proposed an approach integrating bioinspired fiber architectures and varying 3D printing parameters into SMPs, to achieve tunable permanent shape and shape memory properties. The self-folded flower and sequentially deployed smart robotic hand have been developed to demonstrate the feasibility of our method. The proposed bioinspired SMPs, which is rarely seen in the previous reports, have intriguing fundamental properties and hold great potential for applications in soft actuators, smart textiles, wearable equipment, medical devices, and other intelligent apparatus.

Fiber is a crucial element in biological micro-structural materials. Replication of fiber-reinforced composites with analogous architectures of their natural counterparts has caused widespread academic concern. Recent researches indicate 3D printing technology has the potential to produce biomimetic structural materials. The aim of this study is to develop a process to fabricate fiber-reinforced composites with ordered yet spatially tunable fiber arrangement. Specifically, we present a method to align fibers during the 3D printing of fiber-reinforced composites. A modified slurry-based stereolithography process was developed, and the fibers in the fiber–resin mixture were aligned by Shear force produced during the spreading of slurry. We investigated the influence of relative factors on fiber orientation, and two models were used to uncover the internal mechanism. By controlling the speed and the direction of the moving blade, the patterns that fibers were arranged can be freely programmed. Therefore, we have extracted bioinspired sinusoidal and zigzag design motifs to analyze their mechanical properties compared with non-bioinspired motifs. The proposed method is relatively material agnostic, more efficient and more facile. It thus provides a promising route to fabricate fiber-reinforced composites, and has potential to be adopted in biological structures researches and industrial applications.

Biological materials have fascinating mechanical properties built up from simple basic material blocks. It is worthwhile to learn how biological materials are constructed, and to apply the knowledge in advanced manufacturing, and to realize new materials by design. In this study, we chose the tubular cell in the soft wood as a biological prototype, and tried to mimic its intelligent construction principle to regulate the compression mechanical behavior through the helical structure. First, by using the multi-material three-dimensional printing technology, we fabricated a series of tubular composites with the helix fibers of a rigid plastic embedded into an elastomeric matrix. Then, through the uniaxial compression tests, we characterized the mechanical behavior of the specimens, having different fiber angle from 0 to 50 deg at constant volume fraction. The results showed that both stiffness and fracture toughness of the printed composite could be regulated effectively by adjusting the fiber angle of the helical structure. Moreover, the helical structure with high fiber angle is able to improve the compression stability of the tubular composite with big lumen. In addition, for the biomimetic composites, the volume fraction of the reinforcements should exceed 40%. Finally, we proposed a new structural design method by combining the reinforcements of different architectures into a double-layered configuration. The intelligent strategy is proven to balance the conflict between the stiffness and toughness of the composites to some extent, and without changing in the building constituents.

Currently, four-dimensional (4D) printing programming methods are mainly structure-based, which usually requires more than one material to endow products with site-specific attributes. Here, we propose a new 4D printing programming approach that enables site-specific shape-morphing behaviors in a single material by regulating the printing parameters. Specifically, a direct ink writing three-dimensional (3D) printer with the ability to change printing parameters (e.g., deposition speed) on the fly is reported. By site-specifically adjusting print speed and print path to control the local nematic arrangements of printed liquid crystal elastomers (LCEs), the shape-morphing behaviors of the LCEs can be successfully programmed. In this way, locally programmed popping-up, self-assembling, and oscillating behaviors can be designed by varying the print speed in specific regions. Snake-like curling is realized by uniformly boosting the print speed in a single line. Furthermore, two theories and an ultrasound image diagnostic apparatus are employed to reveal the mechanism behind this behavior. This work provides a feasible way to realize the gradient transition of material properties through a single material. It broadens the design space and pushes the envelope of 4D printing, which is expected to be helpful in the fabrication of soft robotics and flexible electronics.

Programmable nonuniform deformation is of great significance for self-shape-morphing systems that are commonly seen in biological systems and also has practical applications in drug delivery, biomedical devices and robotics, etc. Here, we present a novel gradient four-dimensional (4D) printing method toward biomimetic nonuniform, dual-stimuli self-morphing. By modeling and printing graded active materials with water swelling properties, we can configure continuously smooth gradients of volume fraction of the active material in bilayer structures. The variation of swelling ratio mismatch between the two layers can be delicately regulated, which results in the programmable nonuniform shape transformation. The shape-shifting results can be predicted by the established mathematical model and computational simulations. Furthermore, we demonstrate dual-stimuli self-morphing structures by printing the graded water-responsive elastomer materials onto a heat-shrinkable shape memory polymer, which could produce different shape changes in response to humidity and different temperatures. This method pioneers a versatile approach to broaden the design space for 4D printing and will be compatible with a wide range of active materials meeting various requirements in diverse potential applications.

Meniscal injury is more likely to cause a permanent alteration of the biomechanical and biological environment of the knee joint, mainly due to the morphological mismatch and substantial loss of meniscal tissues. Herein, to overcome this challenge, we developed an improved bioink with enhanced printability, while maintaining the biocompatibility of major cellular component of the meniscus, namely fibrochondrocytes. Firstly, cellulose nanofiber (CNF) was mixed with gelatin-alginate thermal-responsive bioinks to improve the printability. Afterward, individual-specific meniscal prototypes based on the 3D reconstruction of MRI data were bioprinted using our bioink. The rheological and printability properties of the bioinks were characterized to select proper bioink content and bioprinting parameters. And then, a series of biological characterizations of the bioprinted samples, such as cell viability, metabolic activity, and extracellular matrix accumulation, were carried out in vitro. The results indicated that superior rheological performance and printability of CNF-modified bioink were achieved, ensuring high-precision bioprinting of specific-designed meniscal prototype when compared with the non-CNF-containing counterparts. Meanwhile, biological tests indicated that fibrochondrocytes encapsulated within the CNF-modified bioink maintained long-term cellular viability as well as acceptable extracellular matrix accumulation. This study demonstrates that the CNF-modified bioink is in favor of the printing fidelity of specific meniscus by improved rheological properties, minimizing the mismatch between artificial meniscal implants and native knee joint tissues, thereby permitting the evolution of clinical therapeutic methods of meniscal reconstruction.

In the natural composites, the reinforcement particles are subtly organized into complex structures in matrix, and its various microstructures endow the biomaterials with a variety of excellent mechanical behaviors. Among the various reinforcement building blocks used in biomaterials, short fibers are the most ubiquitous reinforcement elements. Unfortunately, because of the limitation of fabrication technique, replication of these fiber-reinforced biological composites can be extremely difficult in practice. In this paper, we developed a fiber assembly 3D printing process, which can manipulate the orientation of fibers during 3D printing procedure. Benefiting from this technology, the reinforcement particles were manipulated remotely and the arrangement of reinforcement particles with higher degree of freedom was achieved. Subsequently, based on the herringbone-modified helicoidal architecture of mantis shrimp, the bio-inspired composites with various microstructures were reconstructed by 3D magnetic printing. In addition, the influence of microstructure type and parameters of bio-inspired composites on the properties of composites was studied systematically, and the quantitative relationship between microstructure and properties of the composites was established. The results show that the impact resistance and compression resistance of the composites can be significantly improved by the simple internal microstructures design, and the regression model established in this article can be used for accurate prediction of composites properties and the reliability is higher. In a word, this study opens a new route for the design of composites with unusual features.