A General Strategy for Sustainable 3D Printing Based on A Multifunctional Photoinitiator.

A multifunctional photoinitiator is presented, offering precise control over light-induced polymerization initiation at 450 nm and material degradation at 365 nm. This is accomplished by covalently linking photoactive bis(acyl)phosphane oxide and photocleavable o-nitrobenzyl ether moieties onto the surface of γ-cyclodextrin. Upon degradation, the resulting linear polymers can be easily re-dissolved in their corresponding monomer and re-cured, exhibiting superior mechanical properties compared to the pristine material. Moreover, this photoinitiator enables the successful 3D printing of intricate and precise structures, representing a promising general strategy for developing recyclable photoresins for 3D printing applications.

In situ bioprinting of double network anti-digestive xanthan gum derived hydrogel scaffolds for the treatment of enterocutaneous fistulas.

The clinical treatment of enterocutaneous fistula is challenging and causes significant patient discomfort. Fibrin gel can be used to seal tubular enterocutaneous fistulas, but it has low strength and poor digestion resistance. Based on in situ bioprinting and the anti-digestive properties of xanthan gum (XG), we used carboxymethyl chitosan (CMC) and xanthan gum modified by grafted glycidyl methacrylate (GMA) and aldehyde (GCX) as the ink to print a double network hydrogel that exhibited high strength and an excellent anti-digestive performance. In addition, in vitro studies confirmed the biocompatibility, degradability, and self-healing of hydrogels. In our rabbit tubular enterocutaneous fistula model, the in situ printed hydrogel resisted corrosion due to the intestinal fluid and acted as a scaffold for intestinal mucosal cells to proliferate on its surface. To summarize, in situ bioprinting GCX/CMC double network hydrogel can effectively block tubular enterocutaneous fistulas and provide a stable scaffold for intestinal mucosal regeneration.

A click chemistry-mediated all-peptide cell printing hydrogel platform for diabetic wound healing.

High glucose-induced vascular endothelial injury is a major pathological factor involved in non-healing diabetic wounds. To interrupt this pathological process, we design an all-peptide printable hydrogel platform based on highly efficient and precise one-step click chemistry of thiolated γ-polyglutamic acid, glycidyl methacrylate-conjugated γ-polyglutamic acid, and thiolated arginine-glycine-aspartate sequences. Vascular endothelial growth factor 165-overexpressed human umbilical vein endothelial cells are printed using this platform, hence fabricating a living material with high cell viability and precise cell spatial distribution control. This cell-laden hydrogel platform accelerates the diabetic wound healing of rats based on the unabated vascular endothelial growth factor 165 release, which promotes angiogenesis and alleviates damages on vascular endothelial mitochondria, thereby reducing tissue hypoxia, downregulating inflammation, and facilitating extracellular matrix remodeling. Together, this study offers a promising strategy for fabricating tissue-friendly, high-efficient, and accurate 3D printed all-peptide hydrogel platform for cell delivery and self-renewable growth factor therapy.

Three filters for the enhancement of the images acquired from fluorescence microscope and weak-light-sources and the image compression.

Fluorescence images enhancement is important as it can provide more information for medical diagnosis. In this work, we design three simple yet useful filters based on the combinations of mathematical functions, which are proved to be effective in strengthening the images acquired from the fluorescence microscope. Using these filters, detailed objects can be found in the dark sections of the fluorescence images. In addition, these filters can be used to enhance the low-light image, which provide satisfactory visual information and marginal profile for the blurred objects in the image. Moreover, these filters have been used to enhance the image with high degradation by the Gaussian noise, where clear edge profile can be extracted. Finally, we have shown that these filters can be utilized for the image compression. Compression ratio can be obtained to be 0.9688. This study shows the making of the filters with dual functions for the image enhancement and the image compression. Our designed filters are showing the potentials in the field of biomedical imaging and pattern identification.

Microfluidic intestinal organoid-on-a-chip uncovers therapeutic targets by recapitulating oxygen dynamics of intestinal IR injury.

Increasing evidence demonstrates that mammals have different reactions to hypoxia with varied oxygen dynamic patterns. It takes ∼24 h for tri-gas incubator to achieve steady cell hypoxia, which fails to recapitulate ultrafast oxygen dynamics of intestinal ischemia/reperfusion (IR) injury. Inspired from the structure of native intestinal villi, we engineered an intestinal organoid chip embedded with engineered artificial microvessels based on co-axial microfluidic technology by using pH-responsive ZIF-8/sodium alginate scaffold. The chip was featured on: (i) eight times the oxygen exchange efficiency compared with the conventional device, tri-gas incubator, (ii) implantation of intestinal organoid reproducing all types of intestinal epithelial cells, and (iii) bio-responsiveness to hypoxia and reoxygenation (HR) by presenting metabolism disorder, inflammatory reaction, and cell apoptosis. Strikingly, it was found for the first time that Olfactomedin 4 (Olfm4) was the most significantly down-regulated gene under a rapid HR condition by sequencing the RNA from the organoids. Mechanistically, OLFM4 played protective functions on HR-induced cell inflammation and tissue damage by inhibiting the NF-kappa B signaling activation, thus it could be used as a therapeutic target. Altogether, this study overcomes the issue of mismatched oxygen dynamics between in vitro and in vivo, and sets an example of next-generation multisystem-interactive organoid chip for finding precise therapeutic targets of IR injury.

Development of high internal phase emulsions with noncovalent crosslink of soy protein isolate and tannic acid: Mechanism and application for 3D printing.

In this study, we propose a design strategy using soy protein isolate (SPI)-tannic acid (TA) complexes crosslinked through noncovalent interactions to develop high internal phase emulsions (HIPEs) for 3D printing materials. The results of Fourier transform infrared spectroscopy, intrinsic fluorescence, and molecular docking analyses indicated that the dominant interactions occurring between the SPI and TA were mediated by hydrogen bonds and hydrophobic interactions. The secondary structure, particle size, ζ-potential, hydrophobicity and wettability of SPI was significantly altered by the addition of TA. The microstructure of HIPEs stabilized by SPI-TA complexes exhibited more regular and even polygonal shapes, thereby allowing the protein to form a dense self-supporting network structure. When the concentration of TA exceeded 50 µmol/g protein, the formed HIPEs remained stable after 45 days of storage. Rheological tests revealed that the HIPEs exhibited a typical gel-like (G' > G'') and shear-thinning behavior, which contributed to preferable 3D printing behavior.

Image Enhancement via Special Functions and Its Application for Near Infrared Imaging.

Image enhancement is important given that it can be used to highlight the area of interest in the images. This article designs four filters via special function for realizing image enhancement. Firstly, a filter based on the exponential function is designed. When the value of the progression is even, the edge feature can be extracted. When the value of the progression is odd, sharp contrast can be obtained. Secondly, a filter is built using hyperbolic cosine and its inverse function, where a printmaking feature can be extracted. Thirdly, a filter is made via a hyperbolic secant function and its inverse. It can lead to the extraction of image edge. When the progression value is increasing, marginal effect can be found and the brightness is decreasing. Ripple morphology can be found. Fourthly, a filter is constructed through a hyperbolic sine function and its inverse, where marginal features can be extracted. Furthermore, these filters are useful for extracting the marginal features even when a high noise density of 0.9 is added to the original images. They are useful for highlighting the images acquired from near infrared imaging.

Two Filters for Acquiring the Profiles from Images Obtained from Weak-Light Background, Fluorescence Microscope, Transmission Electron Microscope, and Near-Infrared Camera.

Extracting the profiles of images is critical because it can bring simplified description and draw special attention to particular areas in the images. In our work, we designed two filters via the exponential and hypotenuse functions for profile extraction. Their ability to extract the profiles from the images obtained from weak-light conditions, fluorescence microscopes, transmission electron microscopes, and near-infrared cameras is proven. Moreover, they can be used to extract the nesting structures in the images. Furthermore, their performance in extracting images degraded by Gaussian noise is evaluated. We used Gaussian white noise with a mean value of 0.9 to create very noisy images. These filters are effective for extracting the edge morphology in the noisy images. For the purpose of a comparative study, we used several well-known filters to process these noisy images, including the filter based on Gabor wavelet, the filter based on the watershed algorithm, and the matched filter, the performances of which in profile extraction are either comparable or not effective when dealing with extensively noisy images. Our filters have shown the potential for use in the field of pattern recognition and object tracking.

Smart implants: 4D-printed shape-morphing scaffolds for medical implantation.

Biomedical implants have recently shown excellent application potential in tissue repair and replacement. Applying three-dimensional (3D) printing to implant scaffold fabrication can help to address individual needs more precisely. Fourdimensional (4D) printing emerges rapidly based on the development of shape-responsive materials and design methods, which makes the production of dynamic functional implants possible. Smart implants can be pre-designed to respond to endogenous or exogenous stimuli and perform seamless integration with regular/ irregular tissue defects, defect-luminal organs, or curved structures via programmed shape morphing. At the same time, they offer great advantages in minimally invasive surgery due to the small-to-large volume transition. In addition, 4D-printed cellular scaffolds can generate extracellular matrix (ECM)-mimetic structures that interact with the contacting cells, expanding the possible sources of tissue/organ grafts and substitutes. This review summarizes the typical technologies and materials of 4D-printed scaffolds, and the programming designs and applications of these scaffolds are further highlighted. Finally, we propose the prospects and outlook of 4D-printed shape-morphing implants.

Whole Model Path Planning-Guided Multi-Axis and Multi-Material Printing of High-Performance Intestinal Implantable Stent.

The problems of step effects, supporting material waste, and conflict between flexibility and toughness for 3D printed intestinal fistula stents are not yet resolved. Herein, the fabrication of a support-free segmental stent with two types of thermoplastic polyurethane (TPU) using a homemade multi-axis and multi-material conformal printer guided with advanced whole model path planning is demonstrated. One type of TPU segment is soft to increase elasticity, and the other is used to achieve toughness. Owing to advancements in stent design and printing, the obtained stents present three unprecedented properties compared to previous three-axis printed stents: i) Overcoming step effects; ii) Presenting comparable axial flexibility to a stent made of a single soft TPU 87A material, thus increasing the feasibility of implantation; and iii) Showing equivalent radial toughness to a stent made of a single hard TPU 95A material. Hence, the stent can resist the intestinal contractive force and maintain intestinal continuity and patency. Through implanting such stents to the rabbit intestinal fistula models, therapeutic mechanisms of reducing fistula output and improving nutritional states and intestinal flora abundance are revealed. Overall, this study develops a creative and versatile method to improve the poor quality and mechanical properties of medical stents.

The Influence of Annealing on the Microstructural and Textural Evolution of Cold-Rolled Er Metal.

The microstructural and textural evolution of 60% cold-rolling-deformation Er metal (purity ≥ 99.7%) during annealing were investigated by electron-backscattered diffraction (EBSD) and X-ray diffraction (XRD). The research results showed that the texture of the (0001) plane orientation was strengthened, but there was no apparent enhancement of the (011¯0) and (1¯21¯0) plane orientations with increasing the annealing temperature. The recrystallization frequency and grain sizes gradually stabilized after the annealing duration of more than 1 h at 740 °C; the annealing duration and the recrystallization frequency were fitted to the equation: y=1 − exp (−0.3269x0.2506). HAGBs were predominant, and the distribution of grain sizes was the most uniform after annealing at 740 °C × 1 h, which was the optimal annealing process of the Er metal with 60% cold-rolling deformation. However, the recrystallization was transferred to the substructure due to grain boundary migration and twining under an excessive annealing temperature and duration.

Synthesis of Holmium-Oxide Nanoparticles for Near-Infrared Imaging and Dye-Photodegradation.

The development of multifunctional nanomaterials has received growing research interest, thanks to its ability to combine multiple properties for severing highly demanding purposes. In this work, holmium oxide nanoparticles are synthesized and characterized by various tools including XRD, XPS, and TEM. These nanoparticles are found to emit near-infrared fluorescence (800-1100 nm) under a 785 nm excitation source. Imaging of the animal tissues was demonstrated, and the maximum imaging depth was found to be 2.2 cm. The synthesized nanoparticles also show the capability of facilitating dye (fluorescein sodium salt and rhodamine 6G) degradation under white light irradiation. The synthesized holmium oxide nanoparticles are envisioned to be useful for near-infrared tissue imaging and dye-degradation.

Effect of Cold Rolling and Annealing on the Microstructure and Texture of Erbium Metal.

Erbium metal with purity ≥ 99% was cold rolled to 30%, 40%, 50%, and 60% deformations and the Er metal of 60% deformation was annealed at different temperatures for 1 h. The effect of cold rolling deformation and annealing on the microstructure and texture evolution of Er metal was investigated by XRD, EBSD, Microhardness tester, and OM. P is the orientation index, which is used to judge the preferred orientation. The research results showed that grains were broken and refined gradually with increasing deformation, the average grain size was 3.37 µm, and the orientation distribution was uniform for 60% deformation; deformation twins appeared in the grain when the deformation was less than 40%, which contributed to the generation of (0001) plane orientation. Comparing with the initial state, the (011-0) plane orientation gradually weakened and the (111-0) plane orientation had a trend of further strengthening with the increasing deformation; the (1-21-0) plane orientation remained unchanged, but there was a gradual weakening trend when the deformation was greater than 50%. For 60% deformation of Er metal, the deformed microstructure was replaced by fine equiaxed grains with the increasing annealing temperature, and the high-performance Er metal with fine and uniform equiaxed grains can be obtained under annealing at 740 °C for 1 h.

Fabrication of gelatin-based printable inks with improved stiffness as well as antibacterial and UV-shielding properties.

Gelatin-based inks have a broad range of applications in bioprinting for tissue engineering and regenerative medicine due to their biocompatibility, ease of modification, degradability, and rapid gelation induced by low temperature. However, gelatin-derived inks prepared through low-temperature treatment have poor mechanical properties that limit their applications. To solve this problem, we designed polyacrylamide/gelatin/silver nanoparticle (PAAm-GelatinAgNPs) ink to improve gelatin-based hydrogels. The ink is based on double networks, in which the physically cross-linked gelatin as the first network and covalently cross-linked PAAm as the second network. It was found that the presence of PAAm increased the tensile and compression strength of the gelatin-based ink. Moreover, silver nanoparticles endowed the antibacterial properties to the gelatin-based ink and were able to shield the UV irradiation and damages to rat skin. In addition, this ink showed the shear thinning property; Consequently it succeeded in printing complex 3D scaffolds such as the cube, five-pointed star, flower, and university logo of "SEU". In summary, this ink presents a new strategy for the modification of gelatin and offers new potential applications for customized therapy of antimicrobial and anti-UV damage to tissues.

Marine-inspired molecular mimicry generates a drug-free, but immunogenic hydrogel adhesive protecting surgical anastomosis.

Herein, we report the synthesis of a biomimic hydrogel adhesive that addresses the poor healing of surgical anastomosis. Dopamine-conjugated xanthan gum (Da-g-Xan) is fabricated using deep insights into the molecular similarity between mussels' adhesive and dopamine as well as the structural similarity between barnacle cement proteins and xanthan gum. The hydrogel mimics marine animals' adherence to wet tissue surfaces. Upon applying this adhesive to colonic anastomosis in a rat model, protective effects were shown by significantly improving the bursting pressure. Mechanistically, the architecture of Da-g-Xan hydrogel is maintained by dynamic intermolecular hydrogen bonds that allow the quick release of Da-g-Xan. The free Da-g-Xan can regulate the inflammatory status and induce type 2 macrophage polarization (M2) by specifically interacting with mannose receptors (CD206) revealed by RNA-sequencing and molecular binding assays. Consequently, an appropriate microenvironment for tissue healing is created by the secretion of chemokines and growth factors from M2 macrophages, strengthening the fibroblast migration and proliferation, collagen synthesis and epithelial vascularization. Overall, this study demonstrates an unprecedented strategy for generating an adhesive by synergistic mimicry inspired by two marine animals, and the results show that the Da-g-Xan adhesive augments native tissue regenerative responses, thus enabling enhanced recovery following surgical anastomosis.

Biomaterials and biosensors in intestinal organoid culture, a progress review.

As an emerging technology, intestinal organoids are promising new tools for basic and translational research in gastroenterology. Currently, culture of intestinal organoids relies mostly on a type of tumor-derived scaffolds, namely Matrigel, which may pose tumorigenic risks to organoid implantation. Apart from the traditional detection methods, such as tissue slicing and fluorescence staining, the monitoring of intestinal organoids requires real-time biosensors that can adapt to their three-dimensional dynamic growth patterns. In this review, we summarized the recent advances in developing definite hydrogel scaffolds for intestinal organoid culture and identified key parameters for scaffold design. In addition, classified by different substrate compositions like pH, electrolytes, and functional proteins, we concluded the existing live-imaging biosensors and elucidated their underlying mechanisms. We hope this review enhances the understanding of intestinal organoid culture and provides more practical approaches to investigate them.

Fabrication of Microfluidic Chips Based on an EHD-Assisted Direct Printing Method.

Microfluidic chips have been widely used in many areas such as biology, environmental monitoring, and micromixing. With the increasing popularity and complexity of microfluidic systems, rapid and convenient approaches for fabricating microfluidic chips are necessary. In this study, a method based on EHD (electrohydrodynamic)-assisted direct printing is proposed. Firstly, the principle of EHD-assisted direct printing was analyzed. The influence of the operating voltage and moving speed of the work table on the width of a paraffin wax model was studied. Then, two kinds of paraffin wax molds for micromixing with channel widths of 120 µm were prepared. A polydimethylsiloxane (PDMS) micromixer was fabricated by replicating the paraffin wax mold, and the micromixing of blue and yellow dye was realized. The results show that EHD-assisted direct printing can be used to make complex microscale structures, which has the potential to greatly simplify the manufacturing process.

Controlled release of silver ions from AgNPs using a hydrogel based on konjac glucomannan and chitosan for infected wounds.

Konjac glucomannan is a biocompatible polysaccharide with high medicinal potential. In this study, we prepared a hydrogel using an optimized crosslinking konjac glucomannan and chitosan. Silver nanoparticles (AgNPs) were incorporated into the hydrogel to enhance its antimicrobial property. This nanocomposite hydrogel could absorb wound exudates due to its swelling ability, and showed self-healing property that enabled structure stability. Moreover, as a carrier, the hydrogel could modulate the release of silver ions burst, thereby reducing AgNPs cytotoxicity. Rats models with infected skin defects were used to assess wound healing. The results indicated that AgNPs hydrogels dressing could promote wound healing and reduce inflammatory response, exhibiting great clinical application potentials.

Synthesizing Ag+: MgS, Ag+: Nb2S5, Sm3+: Y2S3, Sm3+:Er2S3, and Sm3+:ZrS2 Compound Nanoparticles for Multicolor Fluorescence Imaging of Biotissues.

Development of the fluorophores whose fluorescence bands can be flexibly selected is of great interest for biotissue imaging. Compounds of Ag+:MgS, Ag+:Nb2S5, Sm3+:Y2S3, Sm3+:Er2S3, and Sm3+:ZrS2 were obtained through new chemical synthesis. They were characterized by X-ray photoelectron spectroscopy, X-ray diffraction spectroscopy, and transmission electron microscopy. They revealed polychromatic-photoluminescence spectra when excited by 280, 380, 480, 580, 680, and 785 nm light. Especially, near-infrared emission ranging from 800-1100 nm was found upon 785 nm light excitation. A band model was proposed to explain transitions responsible for the observed components of emission. Their broad fluorescence spectra cover from the ultraviolet to near-infrared spectral range. Their ability of emitting wide-range fluorescence was utilized for multicolor fluorescence imaging of biotissues, as demonstrated by pig-kidney tissue samples.

Fabrication of Different Microchannels by Adjusting the Extrusion Parameters for Sacrificial Molds.

Using the 3D printed mold-removal method to fabricate microchannel has become a promising alternative to the conventional soft lithography technique, due to the convenience in printing channel mold and the compatibility with PDMS material. Although having great potential, the use of single filament extruded by fused deposition modeling (FDM) as the sacrificial channel mold has not been elaborately studied. In this paper, we demonstrate the fabrication of microchannels with different structure and size by controllably extruding the sacrificial channel molds. The influences of the main processing parameters including working distance, extrusion amount and printing speed on the printed microchannels are systematically investigated. The results show that, the circular and low-aspect-ratio straight microchannels with different sizes can be fabricated by adjusting the extrusion amounts. The sinusoidal, 3D curved and cross-linked curved microchannels along straight path can be fabricated, either independently or in combination, by the combined control of the working distance, extrusion amount and printing speed. The complex microchannels with different structural features can also be printed along curved serpentine, rectangular serpentine, and spiral paths. This paper presents a simple and powerful method to fabricate the complex microchannels with different structure and size by just controlling the processing parameters for extruding channel molds.