3D printing of milk-based product

We developed a method to perform direct ink writing (DIW) three-dimensional (3D) printing of milk products at room temperature by changing the rheological properties of the printing ink. 3D printing of food products has been demonstrated by different methods such as selective laser sintering (SLS) and hot-melt extrusion. Methods requiring high temperatures are, however, not suitable to creating 3D models consisting of temperature-sensitive nutrients. Milk is an example of such foods rich in nutrients such as calcium and protein that would be temperature sensitive. Cold-extrusion is an alternative method of 3D printing, but it requires the addition of rheology modifiers and the optimization of the multiple components. To address this limitation, we demonstrated DIW 3D printing of milk by cold-extrusion with a simple formulation of the milk ink. Our method relies on only one milk product (powdered milk). We formulated 70 w/w% milk ink and successfully fabricated complex 3D structures. Extending our method, we demonstrated multi-material printing and created food with various edible materials. Given the versatility of the demonstrated method, we envision that cold extrusion of food inks will be applied in creating nutritious and visually appealing food, with potential applications in formulating foods with various needs for nutrition and materials properties, where food inks could be extruded at room temperature without compromising the nutrients that would be degraded at elevated temperatures.

We developed a method to 3D-print milk-based inks at room temperature by changing the rheological properties. The method is based on direct ink writing (DIW) and permits multi-material printing of 3D edible structures.     

Synthesis of a photocurable acrylated poly(ethylene glycol)-co-poly(xylitol sebacate) copolymers hydrogel 3D printing ink for tissue engineering

Photocurable hydrogel scaffolds for tissue engineering must have excellent biocompatibility, tunable mechanical characteristics, and be biodegradable at a controllable rate. Hydrogels developed as ink for 3D printing require several other properties such as optimal viscosity and shorter photocrosslinking time to ensure continuous extrusion and to avoid untimely collapse of the printed structure. Here, a novel photocurable hydrogel made of acrylated poly(ethylene glycol)-co-poly(xylitol sebacate) (PEXS-A) is developed for tissue engineering and 3D printing applications. Synthesis of PEXS-A hydrogel with equilibrated water content above 90% is achieved via a quick and facile photopolymerization process. Changing the acrylation ratio of the PEXS-A hydrogel has an impact on its crosslinking density, mechanical properties and degradation rate, thus highlighting PEXS-A tunability. PEXS-A could be employed as ink as demonstrated by the 3D printing of a 30-layers cubic grid with high structural integrity. Furthermore, 3T3 fibroblast cells encapsulated into PEXS-A during photocrosslinking maintain a viability of 93.76% after seven days, which showed the good biocompatibility of this novel hydrogel. These results indicate that PEXS-A hydrogel could have multiple applications including as 3D printing ink and as tissue engineering scaffold.

A novel acrylated poly(ethylene glycol)-co-poly(xylitol sebacate) (PEXS-A) hydrogel for 3D printing ink and cell encapsulation for tissue engineering application.     

A facile method for fabricating a three-dimensional aligned fibrous scaffold for vascular application

Vascular graft replacement remains the optimal treatment option for many vascular diseases despite advances in endovascular surgery. In this study, we proposed the use of surface topographical cues to align and maintain the phenotype of vascular smooth muscle cells (vSMCs) which were reported as one of the vital limitations for successful graft replacement. An auxiliary electrospinning setup has been developed to collect circumferentially aligned fibres on a 3D tubular format; this micro-architecture was found to be similar to the tunica media layer of blood vessels. The presence of aligned fibres served as a signaling modality to induce cell alignment and the maintenance of the contractile phenotype. vSMCs cultured on the 3D aligned fibrous substrate were found to exhibit better cell proliferation ability and enhanced cell-shape directionality. The functional expression of the two representative intracellular contractile proteins (i.e. α-SMA and MHC) was found to exhibit definitive markers that are orderly organized as microfilament bundles. Collectively, the result suggests a possibility of adapting the 3D aligned tubular scaffold to enhance and regulate cell function along with the additional tunability of scaffold diameter and thicknesses for tailoring to the needs of individual patients or future ex vivo studies.

Collection of circumferentially aligned and 3D fibrous scaffold on a newly designed electrospinning auxiliary jig. The aligned fibres served as a signaling modality to induce cell alignment and the maintenance of a contractile phenotype for hSMCs.     

A three-dimensional hydroxyapatite/polyacrylonitrile composite scaffold designed for bone tissue engineering

In recent years, various composite scaffolds based on hydroxyapatite have been developed for bone tissue engineering. However, the poor cell survival micro-environment is still the major problem limiting their practical applications in bone repairing and regeneration. In this study, we fabricated a class of fluffy and porous three-dimensional composite fibrous scaffolds consisting of hydroxyapatite and polyacrylonitrile by employing an improved electrospinning technique combined with a bio-mineralization process. The fluffy structure of the hydroxyapatite/polyacrylonitrile composite scaffold ensured the cells would enter the interior of the scaffold and achieve a three-dimensional cell culture. Bone marrow mesenchymal stem cells were seeded into the scaffolds and cultured for 21 days in vitro to evaluate the response of cellular morphology and biochemical activities. The results indicated that the bone marrow mesenchymal stem cells showed higher degrees of growth, osteogenic differentiation and mineralization than those cultured on the two-dimensional hydroxyapatite/polyacrylonitrile composite membranes. The obtained results strongly supported the fact that the novel three-dimensional fluffy hydroxyapatite/polyacrylonitrile composite scaffold had potential application in the field of bone tissue engineering.

A fluffy and porous (3D) HA composite fibrous scaffold was fabricated by employing an improved electrospinning technique combined with a bio-mineralization process.     

Three-dimensional printed optical phantoms with customized absorption and scattering properties

Three-dimensional (3D) printing offers the promise of fabricating optical phantoms with arbitrary geometry, but commercially available thermoplastics provide only a small range of physiologically relevant absorption (µ_a) and reduced scattering (µ_s`) values. Here we demonstrate customizable acrylonitrile butadiene styrene (ABS) filaments for dual extrusion 3D printing of tissue mimicking optical phantoms. µ<sub>a</sub> and µ<sub>s</sub>` values were adjusted by incorporating nigrosin and titanium dioxide (TiO₂) in the filament extrusion process. A wide range of physiologically relevant optical properties was demonstrated with an average repeatability within 11.5% for µ_a and 7.71% for µ_s`. Additionally, a mouse-simulating phantom, which mimicked both the geometry and optical properties of a hairless mouse with an implanted xenograft tumor, was printed using dual extrusion methods. 3D printed tumor optical properties matched the live tumor with less than 3% error at a wavelength of 659 nm. 3D printing with user defined optical properties may provide a viable method for durable optically diffusive phantoms for instrument characterization and calibration.OCIS codes: (170.5280) Photon migration, (110.0113) Imaging through turbid media, (110.7050) Turbid media, (160.4670) Optical materials     

基于超声的3D打印技术在心脏领域的应用进展

3D打印技术是近年来出现的新技术。随着三维超声的发展,基于超声的3D打印技术在心血管疾病诊断和治疗中逐渐被应用。3D打印技术通过获取图像、建模、实体打印三个步骤可以把三维超声图像转换为实体模型。目前基于超声的3D打印技术主要应用在左心耳封堵术、瓣膜性心脏病、先天性心脏病三个方面,有助于术前评估、术前模拟手术、医疗装置设计、血流动力学模拟及医学沟通教育。3D打印技术应用前景广阔,打印具有生物活性的组织或者结构直接应用于人体是未来的发展方向。为了让3D打印技术更好地服务临床,我们仍面临着巨大的挑战。     

三维重建及打印技术在乳腺肿瘤中的研究进展

目前医学影像技术（超声、钼靶、CT、MRI）在诊断乳腺占位性病变中具有重要价值,对病灶定性诊断具有较高敏感度及准确率。基于医学影像学的三维重建技术及三维打印技术发展迅速,可为术者提供更直观、精确的病变位置、空间解剖结构及形态、容积等信息,为制定手术方案、术后个体化重建及评估化疗效果等提供帮助。本文对基于医学影像学的三维重建及打印技术在乳腺占位性病变诊疗中的研究进展进行综述。     

Electrospinning of pyrazole-isothiazole derivatives: nanofibers from small molecules

We investigate the electrospinning of small molecules, specifically designed peptide derivatives of the pyrazole-isothiazole scaffold. Such non-natural peptides enhance the spectrum of fundamental materials used for electrospinning. Unlike standard electrospun materials, our peptides are not polymeric, but able to aggregate in solution and especially during processing. They contain donor/acceptor groups that can form hydrogen bonds, and groups that are able to generate π-stacking interactions, which are known as important requirements for assembly processes. The pyrazole-isothiazole derivatives were synthesized by means of a 1,3-dipolar cycloaddition reaction, which is completely regioselective, affording only one isomer. We demonstrate that our compounds can be electrospun from fluoroalcohol solution into solid, quasi-endless micro- and nanofibers. The electrospinnability varies substantially, depending on the amino acids linked to the scaffold. Some compounds provide only short fibers, while Fmoc-glycyl-(N-benzyl)-pyrazole-isothiazole-tert-butyl carboxylate-1,1-dioxide forms continuous, homogenous, and bead-free fibers (droplet-like beads are a common problem in electrospinning). We analyzed the compounds and the fibers with various spectroscopic techniques (MS, IR and Raman). Electrospinning does not change chemical composition and configuration, suggesting the monomeric form of the compounds even in the fibers. Interestingly, we found that the stereochemistry of the scaffold can affect the ability of the peptide to be electrospun.

Pyrazole-isothiazole monomers are electrospun from solution into solid, quasi-endless micro- and nanofibers.     

Biomimetic cellulose/calcium-deficient-hydroxyapatite composite scaffolds fabricated using an electric field for bone tissue engineering

Cellulose has been widely used as micro/nanofibers in various applications of tissue regeneration, but has certain limitations for bone regeneration, e.g., low biocompatibility in inducing osteogenesis. In addition, the low processability from the decomposition property before melting can be a significant obstacle to fabricating a required complex structure through a 3D-printing process. Herein, to overcome the low osteogenic activity of pure cellulose, we suggest a new cellulose-based composite scaffold consisting of cellulose and a high weight fraction (70 wt%) of calcium-deficient-hydroxyapatite (CDHA), which was obtained from the hydrolysis of α-tricalcium phosphate. Using biocompatible components, we fabricated a 3D pore-structure controllable composite scaffold consisting of microfibrous bundles through an electrohydrodynamic printing (EHDP) process supplemented with an ethanol bath. To obtain a mechanically stable and repeatable 3D mesh structure, various process parameters (nozzle-to-target distance, electric field strength, flow rate, and nozzle moving speed) were considered. As a control, a mesh structure fabricated using a normal EHDP process and with a similar pore geometry was used. A variety of cellular responses using preosteoblasts (MC3T3-E1) indicate that a CDHA/cellulose composite scaffold provides an efficient platform for inducing significantly high bone mineralization.

The fabricated ceramic scaffold showed a layer-by-layered mesh structure entangled with cellulose micro/nanofibers and the bioceramic phase. By varying processing parameters, the unique 3D fibrous mesh-structure could be achieved.     

Study on the enhancing water collection efficiency of cactus- and beetle-like biomimetic structure using UV-induced controllable diffusion method and 3D printing technology

Collecting water from fog flow has emerged as a promising strategy for the relief of water shortage problems. Herein, using a UV-induced (ultraviolet light induced) controllable diffusion method combined with technology of three-dimensional (3D) printing, we fabricate biomimetic materials incorporating beetle-like hydrophobic–hydrophilic character and cactus-like cone arrays with various structure parameters, and then systematically study their fog-harvesting performance. The UV-induced controllable diffusion method can break away from the photomask to regulate the hybrid wettability. Moreover, employing 3D printing technology can flexibly control the structure parameters to improve the water collection efficiency. It is found that the water collection rate (WCR) can be optimized by controlling the hybrid wettability of the sample surface and cone distance and using substrates with printed holes, which lead to a 109% increase of WCR.

A simple UV-induced controllable diffusion method and 3D printing technology are utilized to create high-efficiency biomimetic water collectors with different beetle-like superhydrophobic–superhydrophilic characters and a cactus-like cone array.     

Electrospun fibers and their application in drug controlled release,biological dressings,tissue repair,and enzyme immobilization

Electrospinning is a method of preparing microfibers or nanofibers by using an electrostatic force to stretch the electrospinning fluid. Electrospinning has gained considerable attention in many fields due to its ability to produce continuous fibers from a variety of polymers and composites in a simple way. Electrospun nanofibers have many merits such as diverse chemical composition, easily adjustable structure, adjustable diameter, high surface area, high porosity, and good pore connectivity, which give them broad application prospects in the biomedical field. This review systematically introduced the factors influencing electrospinning, the types of electrospun fibers, the types of electrospinning, and the detailed applications of electrospun fibers in controlled drug release, biological dressings, tissue repair and enzyme immobilization fields. The latest progress of using electrospun fibers in these fields was summarized, and the main challenges to be solved in electrospinning technology were put forward.

Electrospun fibers have gained considerable attention in drug controlled release, biological dressings, tissue repair and enzyme immobilization fields.     

Aqueous-based electrospun P(NIPAAm-co-AAc)/RSF medicated fibrous mats for dual temperature- and pH-responsive drug controlled release

This paper presents a green method for fabricating dual temperature- and pH-responsive electrospun fibrous mats from an aqueous-based blend poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPAAm-co-AAc)) and regenerated silk fibroin (RSF) by employing electrospinning technique. P(NIPAAm-co-AAc) was synthesized by free radical solution polymerization and its low critical solution temperature (LCST) was in the physiological range (38.8 °C). The P(NIPAAm-co-AAc)/RSF fibers were prepared by electrospinning technology in the presence of the crosslinking agents (EDC·HCl and NHS) with water as solvent. After in situ crosslinking and water-annealing process, the water-stable composite fibrous mats were obtained. Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) were used to analyze the crosslinking process. Temperature and pH dual stimuli-responsive swelling-shrinking behavior of the fibrous mats were observed when the temperature was below and above the LCST of the copolymer at different pHs. In addition, rhodamine B-loaded the fibrous mats also showed dual temperature and pH controlled release behavior, demonstrating the potential use of the fibrous mats for “smart” controlled drug delivery applications.

This paper presents a green friendly method for preparing dual temperature- and pH-responsive electrospun P(NIPAAm-co-AAc)/RSF fibrous mats for drug release.     

Start-up stage with improved resolution for an electric field-assisted fused deposition

Electric field-assisted fused deposition modeling (E-FDM) is a promising technique in the field of 3D printing. This paper studies the start-up stage of the printing, which is a process of liquid gradually deforming and making an initial contact with the substrate under the action of electric stress. Polycaprolactone, a popular material for biomedicine, is selected as the printing material. With a home-built E-FDM system, the nozzle-to-substrate distance and the nozzle and substrate temperatures are all held steady. With a photography system, the process of meniscus deformation is recorded. And by image processing methods, the meniscus length and the volume of liquid at the nozzle can be obtained. At a set of initial liquid volumes (V_i), nozzle voltage is ramped to a fixed value at a fixed rate. The effects of V_i on the meniscus deformation during the start-up stage of the printing are examined. For sufficiently small V_i, the meniscus deforms into a conical (Taylor cone) shape, and a fine jet with a diameter much smaller than the nozzle diameter appears. For sufficiently large V_i, the meniscus exhibits a spindle shape when it touches the substrate. At an intermediate V_i, a Taylor cone is formed, tending to eject a fine jet. After a short period of stagnation or even a slight retraction, no liquid is emitted. Through this study, it is suggested that for high-resolution printing, ramping the voltage at small V_i may be preferable. This proposition is preliminarily confirmed in a direct writing test.

Electric field-assisted fused deposition modeling (E-FDM) is a promising technique in the field of 3D printing.     

An anisotropic three-dimensional electrospun micro/nanofibrous hybrid PLA/PCL scaffold

Although the electrospinning method has been developed to prepare nanofibrous scaffolds, their isotropic structure, low porosity and small pore size prevents them from wide application, especially for anisotropic tissues. In this study, a modified electrospinning receiving system with a rotating mandrel and a water bath is developed. Compared with the nanofibrous scaffold prepared by the common electrospinning system, the micro/nanofibrous polylactide/polycaprolactone (PLA/PCL) hybrid scaffold obtained with the modified system presents anisotropic structure, promotes porosity and enlarged pore size. The hybrid scaffold consists of oriented microfibers and random nanofibers. SEM images demonstrate its anisotropic 3D structure. Tensile testing results confirm that the hybrid scaffold has anisotropic mechanical properties. Compared with the nanofibrous scaffold, human osteoblast-like MG-63 cells protrude more on the surface of the hybrid scaffold. Actin fluorescence staining confirms that the cells form more actin filaments inside the hybrid scaffold. HE staining indicates that more cells enter the interior of the micro/nanofibrous hybrid scaffold. The CCK-8 activity test shows an enhanced proliferation activity of cells on the surface of the hybrid scaffold. In conclusion, the novel micro/nanofibrous hybrid scaffold has an anisotropic structure and better biocompatibility than common nanofibrous scaffolds, indicating a promising future for use in anisotropic tissue engineering.

A modified electrospinning receiving system is developed to prepare a micro/nanofibrous polylactide/polycaprolactone (PLA/PCL) hybrid scaffold with anisotropic structure and better biocompatibility.     

基于医学影像学的3D打印技术在心血管疾病诊疗中的应用现状及研究进展

3D打印技术作为一种快速成型技术,近年来在心血管领域应用广泛。3D打印模型的制作有多种方式,不同的成型方式有各自的优缺点。在先天性心脏病、心脏瓣膜病、大血管病变、心律失常的诊疗过程中3D打印发挥着重要的作用。本文基于医学影像学的3D打印技术在心血管疾病诊疗中的应用现状和研究进展进行综述。     

Stable multi-jet electrospinning with high throughput using the bead structure nozzle

A modified bead structure nozzle for the electrospinning process was developed to improve the production efficiency of nanofibers and facilitate the cleaning of equipment. The effects of the flow rate, voltage and receiving distance on the number of jets were studied. The results indicate that the number of stable jets can be effectively controlled by spinning conditions. The rotating spinning phenomenon, which occurred during spinning, was subjected to force analysis. The COMSOL Multiphysics model was applied to simulate the electric field to show that the bead structured nozzle does not change the overall spinning electric field compared with traditional spinning. The results indicate that the bead structure nozzle can produce a stable multi-jet using a curved surface structure and improve the production efficiency of nanofibers. Compared with the high-voltage conditions of needleless spinning, the bead-type nozzle helps to save energy and facilitate cleaning, so as to avoid the production of waste in experimental research and industrial production.

A modified bead structure nozzle for the electrospinning process was developed to improve the production efficiency of nanofibers and facilitate the cleaning of equipment.     

A review of key challenges of electrospun scaffolds for tissue‐engineering applications

Tissue engineering holds great promise to develop functional constructs resembling the structural organization of native tissues to improve or replace biological functions, with the ultimate goal of avoiding organ transplantation. In tissue engineering, cells are often seeded into artificial structures capable of supporting three‐dimensional (3D) tissue formation. An optimal scaffold for tissue‐engineering applications should mimic the mechanical and functional properties of the extracellular matrix (ECM) of those tissues to be regenerated. Amongst the various scaffolding techniques, electrospinning is an outstanding one which is capable of producing non‐woven fibrous structures with dimensional constituents similar to those of ECM fibres. In recent years, electrospinning has gained widespread interest as a potential tissue‐engineering scaffolding technique and has been discussed in detail in many studies. So why this review? Apart from their clear advantages and extensive use, electrospun scaffolds encounter some practical limitations, such as scarce cell infiltration and inadequate mechanical strength for load‐bearing applications. A number of solutions have been offered by different research groups to overcome the above‐mentioned limitations. In this review, we provide an overview of the limitations of electrospinning as a tissue‐engineered scaffolding technique, with emphasis on possible resolutions of those issues. Copyright © 2015 John Wiley & Sons, Ltd.     

3D printing of biomass-derived composites: application and characterization approaches

Three-dimensional (3D) printing is an additive manufacturing technique with a wide range of 3D structure fabrication and minimal waste generation. Recently, lignocellulosic biomass and its derivatives have been used in 3D printing due to their renewable nature and sustainability. This review provides a summary of the development of different types of biomass and its components such as cellulose and lignin in 3D printing, brief data analysis and introduction to characterization methods of the 3D printed composites. Mechanical properties such as tensile properties, Izod impact properties, and flexural properties, thermal properties and morphological properties of 3D-printed composites are discussed. In addition, other available characterization methods of 3D-printed composites are reported. The future direction of biomass and its derivatives in the field of 3D printing is also discussed.

Biomass-derived 3D printing has attracted interests because of its developing technology and availability with renewable materials as well as compatible characteristics for many applications.     

Bone apatite anisotropic structure control via designing fibrous scaffolds

Bone tissue has an anisotropic structure, associated with the collagen fibrils'' orientation and the c-axis direction of the bone apatite crystal. The bone regeneration process comprises two main phases: bone mineral density restoration (bone quantity), and subsequent recovery of bone apatite c-axis orientation (bone quality). Bone quality is the determinant factor for mechanical properties of bone. Control of osteoblast alignment is one of the strategies for reconstructing bone quality since the collagen/apatite matrix orientation in calcified tissues is dependent on the osteoblast orientation. In this work, fibrous scaffolds designed for reconstruction of bone quality via cell alignment control was investigated. The fibrous scaffolds were fabricated using the electrospinning method with poly(lactic acid) at various fiber collecting speeds. The degree of fiber alignment in the prepared fibrous scaffolds increased with increasing fiber collecting speed, indicating that the fibers were oriented in a single direction. The alignment of osteoblasts on the fibrous scaffolds as well as the subsequent apatite c-axis orientation increased with increasing fiber collecting speed. We successfully controlled cell alignment and apatite c-axis orientation using the designed morphology of fibrous scaffolds. To the best of our knowledge, this is the first report demonstrating that adjusting the degree of fiber orientation for fibrous scaffolds can manipulate the regeneration of bone quality.

Osteoblast alignment on the fibrous scaffolds as well as the subsequent apatite c-axis orientation increased with increasing fiber collecting speed. We successfully controlled cell alignment and apatite c-axis orientation using the designed morphology of fibrous scaffolds.     

Preparation of thermo-responsive drug-loaded nanofibrous films created by electrospinning

We prepared thermosensitive and biocompatible drug-loaded nanofibrous films by an electrospinning technique using a block copolymer, poly(N-isopropylacrylamide)-b-poly(l-lactide) (PNLA), and poly(l-lactide) (PLLA). The copolymer PNLA was synthesized by the radical polymerization of N-isopropylacrylamide (NIPAAm), followed by the ring-opening polymerization of l-lactide. The properties of PNIPAAm and PNLA were selectively discussed based on the results of NMR, FT-IR, GPC, and CA analyses. Because of the low molecular weight of PNIPAAm and PNLA and the hydrolysis of PNLA resulting from its hydrophilicity, these copolymers were inappropriate for electrospinning separately. Hence, a mixture of PNLA and PLLA was used to prepare electrospun nanofibrous films. SEM images of the PNLA/PLLA electrospun films showed that homogeneous fibres with smooth surfaces were obtained. In vitro release studies indicated that the drug-release rate of the PNLA/PLLA electrospun nanofibrous films can be adjusted by the content and molecular weight of PNLA and by the environmental temperature. The results demonstrate that electrospinning is a promising way to create stimuli-responsive fibrous films with potential applications in the design of controllable drug delivery systems.

Thermosensitive and biocompatible PNLA/PLLA drug-loaded nanofibrous films with different morphologies and controlled drug release behaviors by electrospinning technique.