3D Printed Polycaprolactone Carbon Nanotube Composite Scaffolds for Cardiac Tissue Engineering

Fabrication of tissue engineering scaffolds with the use of novel 3D printing has gained lot of attention, however systematic investigation of biomaterials for 3D printing have not been widely explored. In this report, well‐defined structures of polycaprolactone (PCL) and PCL‐ carbon nanotube (PCL‐CNT) composite scaffolds have been designed and fabricated using a 3D printer. Conditions for 3D printing has been optimized while the effects of varying CNT percentages with PCL matrix on the thermal, mechanical and biological properties of the printed scaffolds are studied. Raman spectroscopy is used to characterise the functionalized CNTs and its interactions with PCL matrix. Mechanical properties of the composites are characterised using nanoindentation. Maximum peak load, elastic modulus and hardness increases with increasing CNT content. Differential scanning calorimetry (DSC) studies reveal the thermal and crystalline behaviour of PCL and its CNT composites. Biodegradation studies are performed in Pseudomonas Lipase enzymatic media, showing its specificity and effect on degradation rate. Cell imaging and viability studies of H9c2 cells from rat origin on the scaffolds are performed using fluorescence imaging and MTT assay, respectively. PCL and its CNT composites are able to show cell proliferation and have the potential to be used in cardiac tissue engineering.

     

3D打印微流控芯片技术研究进展

近年来,微流控技术在生命科学和医学诊断等领域得到广泛的应用,显示出了其在检测速度、精度以及试剂损耗等方面相比传统方法的显著优势.然而,使用从半导体加工技术继承而来的微加工技术制作微流控芯片具有比较高的资金和技术门槛,在一定程度上阻碍了微流控技术的推广和应用.近年来随着3D打印技术的兴起,越来越多的研究者尝试使用3D打印技术加工微流控芯片.相比于传统的微加工技术,3D打印微流控芯片技术显示出了其设计加工快速、材料适应性广、成本低廉等优势.本文针对近年来国内外在3D打印微流控芯片领域的最新进展进行了综述,着重介绍了采用微立体光刻、熔融沉积成型以及喷墨打印等3D打印技术加工制作微流控芯片的方法,以及这些微流控芯片在分析化学、生命科学、医学诊断等领域的应用,并对3D打印微流控芯片技术未来的发展进行了展望.     

Fabrication of Stiffness Gradients of GelMA Hydrogels Using a 3D Printed Micromixer

Many properties in both healthy and pathological tissues are highly influenced by the mechanical properties of the extracellular matrix. Stiffness gradient hydrogels are frequently used for exploring these complex relationships in mechanobiology. In this study, the fabrication of a simple, cost‐efficient, and versatile system is reported for creation of stiffness gradients from photoactive hydrogels like gelatin‐methacryloyl (GelMA). The setup includes syringe pumps for gradient generation and a 3D printed microfluidic device for homogenous mixing of GelMA precursors with different crosslinker concentration. The stiffness gradient is investigated by using rheology. A co‐culture consisting of human adipose tissue‐derived mesenchymal stem cells (hAD‐MSCs) and human umbilical cord vein endothelial cells (HUVECs) is encapsulated in the gradient construct. It is possible to locate the stiffness ranges at which the studied cells displayed specific spreading morphology and migration rates. With the help of the described system, variable mechanical gradient constructs can be created and optimal 3D cell culture conditions can be experientially identified.     

Powder Conductivity Assessment Using a Disposable 3D Printed Device

This work describes a low‐cost 3D printed apparatus developed for powder electrical conductivity measurement with electrodes fitted in either a two‐probe or four probe van der Pauw configurations. Electrical conductivity was then measured as a function of density by compressing the powders in an Instron mechanical test machine. Highly conductive carbon black, lower conductive Fe₃O₄ and titania carbon nanotube composites were further tested under both methodologies to assess their reliability. Small powder masses are required for each measurement and our data matched well with literature values. It appeared that 3D printed polymer dies could be used to measure powder conductivity, though loss of material on the die walls was a source of error especially for small powder volumes.     

A Stereolithography‐Based 3D Printed Hybrid Scaffold for In Situ Cartilage Defect Repair

Damage to articular cartilage can over time cause degeneration to the tissue surrounding the injury. To address this problem, scaffolds that prevent degeneration and promote neotissue growth are needed. A new hybrid scaffold that combines a stereolithography‐based 3D printed support structure with an injectable and photopolymerizable hydrogel for delivering cells to treat focal chondral defects is introduced. In this proof of concept study, the ability to a) infill the support structure with an injectable hydrogel precursor solution, b) incorporate cartilage cells during infilling using a degradable hydrogel that promotes neotissue deposition, and c) minimize damage to the surrounding cartilage when the hybrid scaffold is placed in situ in a focal chondral defect in an osteochondral plug that is cultured under mechanical loading is demonstrated. With the ability to independently control the properties of the structure and the injectable hydrogel, this hybrid scaffold approach holds promise for treating chondral defects.     

3D‐Printed Microfluidics

The advent of soft lithography allowed for an unprecedented expansion in the field of microfluidics. However, the vast majority of PDMS microfluidic devices are still made with extensive manual labor, are tethered to bulky control systems, and have cumbersome user interfaces, which all render commercialization difficult. On the other hand, 3D printing has begun to embrace the range of sizes and materials that appeal to the developers of microfluidic devices. Prior to fabrication, a design is digitally built as a detailed 3D CAD file. The design can be assembled in modules by remotely collaborating teams, and its mechanical and fluidic behavior can be simulated using finite‐element modeling. As structures are created by adding materials without the need for etching or dissolution, processing is environmentally friendly and economically efficient. We predict that in the next few years, 3D printing will replace most PDMS and plastic molding techniques in academia.     

Scanning Electrochemical Microscopy (SECM) Investigation of 3D Printed Parts Produced by CMT Welding Technology

In the field of manufacturing technology an exciting revolution is in progress today. The different methods of the so called additive manufacturing (AM) technologies are under fast developments. Several versions of them are called 3D printing. Less interest has been given to study the corrosion resistance character of the differently made 3D printed metal alloy items. In this work corrosion behaviour of 3D printed AlMg4.5Mn0.7 alloy samples were investigated. Conventional methods like open circuit potential measurements, Tafel plots taking and scanning electrochemical microscopy (SECM) – with pH measuring tungsten micro‐tip and micro‐disc type Pt electrode were used. The metal samples were embedded in epoxy resin. 2D SECM images and line scans were made to see the local changes of oxygen concentration. Flame atomic absorption spectroscopy was used for measuring the metal composition of manufacturing wire and printed sample. The local activity of the surface spots were measured using approach curves recorded in case of ferrocene methanol mediator.     

3D Bioprinting of Artificial Tissues: Construction of Biomimetic Microstructures

It is promising that artificial tissues/organs for clinical application can be produced via 3D bioprinting of living cells and biomaterials. The construction of microstructures biomimicking native tissues is crucially important to create artificial tissues with biological functions. For instance, the fabrication of vessel‐like networks to supply cells with initial nutrient and oxygen, and the arrangement of multiple types of cells for creating lamellar/complex tissues through 3D bioprinting are widely reported. The current advances in 3D bioprinting of artificial tissues from the view of construction of biomimetic microstructures, especially the fabrication of lamellar, vascular, and complex structures are summarized. In the end, the conclusion and perspective of 3D bioprinting for clinical applications are elaborated.     

Microfluidic‐Printed Microcarrier for In Vitro Expansion of Adherent Stem Cells in 3D Culture Platform

Microcarrier‐based stem cell expansion cultures can increase the dimensions of in vitro stem cell cultures from 2D to 3D. The culture handling process then becomes more efficient compared with conventional 2D cultures. However, the use of spherical plastic microcarriers complicates the monitoring of cell culture. To facilitate monitoring, transparent disc‐shaped microcarriers are manufactured using a light‐initiated microfluidic printing system and the obtained microcarriers are named as 2.5D microcarrier. The 2.5D microcarriers (diameter/height ≈ 5) enable us to use conventional monitoring tools in 2D‐based platform during the in vitro expansion on a 3D culture platform. Surface modification via a 1 h‐long poly‐dopamine (PDA) reaction can maintain the transparent nature of the microcarriers while optimizing the cell attachment. The surface marker expression and differentiation potential of the 2.5D microcarrier‐expanded stem cells reveal that the characteristics and functionalities preserved during expansion. The 2.5D microcarrier is readily integrated into an on‐bead assay to conserve reagents and permit a high number (n = 9) of repeated measurements with reliable results. These results demonstrate that the 2.5D microcarrier‐based scale‐up culture provides a valuable tool for the in vitro expansion of adherent stem cells, especially if repetitive monitoring is required.     

3D Printed High‐Throughput Hydrothermal Reactionware for Discovery,Optimization, and Scale‐Up

3D printing techniques allow the laboratory‐scale design and production of reactionware tailored to specific experimental requirements. To increase the range and versatility of reactionware devices, sealed, monolithic reactors suitable for use in hydrothermal synthesis have been digitally designed and realized. The fabrication process allows the introduction of reaction mixtures directly into the reactors during the production, and also enables the manufacture of devices of varying scales and geometries unavailable in traditional equipment. The utility of these devices is shown by the use of 3D printed, high‐throughput array reactors to discover two new coordination polymers, optimize the synthesis of one of these, and scale‐up its synthesis using larger reactors produced on the same 3D printer. Reactors were also used to produce phase‐pure samples of coordination polymers MIL‐96 and HKUST‐1, in yields comparable to synthesis in traditional apparatus.     

Chitosan and Whey Protein Bio-Inks for 3D and 4D Printing Applications with Particular Focus on Food Industry

The application of chitosan (CS) and whey protein (WP) alone or in combination in 3D/4D printing has been well considered in previous studies. Although several excellent reviews on additive manufacturing discussed the properties and biomedical applications of CS and WP, there is a lack of a systemic review about CS and WP bio-inks for 3D/4D printing applications. Easily modified bio-ink with optimal printability is a key for additive manufacturing. CS, WP, and WP–CS complex hydrogel possess great potential in making bio-ink that can be broadly used for future 3D/4D printing, because CS is a functional polysaccharide with good biodegradability, biocompatibility, non-immunogenicity, and non-carcinogenicity, while CS–WP complex hydrogel has better printability and drug-delivery effectivity than WP hydrogel. The review summarizes the current advances of bio-ink preparation employing CS and/or WP to satisfy the requirements of 3D/4D printing and post-treatment of materials. The applications of CS/WP bio-ink mainly focus on 3D food printing with a few applications in cosmetics. The review also highlights the trends of CS/WP bio-inks as potential candidates in 4D printing. Some promising strategies for developing novel bio-inks based on CS and/or WP are introduced, aiming to provide new insights into the value-added development and commercial CS and WP utilization.     

Extrusion 3D printing of conjugated polymers

Conjugated polymers combine electronic charge transport properties with the ability to transport ions, enabling transduction between ionic and electronic currents. Many applications of conjugated polymers, such as biointerfaces, actuators, and energy storage, benefit from 3D structures. Among different methods for 3D fabrication, extrusion-based 3D printing is a versatile approach that is compatible with multimaterial fabrication processes. This review summarizes progress in the emerging field of 3D printed conjugated polymers using three extrusion printing processes: direct ink write, meniscus-guided printing, and electrohydrodynamic printing. Ink designs for direct in write are described in depth, including strategies for modifying the rheology and conductivity of the inks.     

Recent Advances in 3D Printing of Photocurable Polymers: Types,Mechanism, and Tissue Engineering Application

The conversion of liquid resin into solid structures upon exposure to light of a specific wavelength is known as photopolymerization. In recent years, photopolymerization-based 3D printing has gained enormous attention for constructing complex tissue-specific constructs. Due to the economic and environmental benefits of the biopolymers employed, photo-curable 3D printing is considered an alternative method for replacing damaged tissues. However, the lack of suitable bio-based photopolymers, their characterization, effective crosslinking strategies, and optimal printing conditions are hindering the extensive application of 3D printed materials in the global market. This review highlights the present status of various photopolymers, their synthesis, and their optimization parameters for biomedical applications. Moreover, a glimpse of various photopolymerization techniques currently employed for 3D printing is also discussed. Furthermore, various naturally derived nanomaterials reinforced polymerization and their influence on printability and shape fidelity are also reviewed. Finally, the ultimate use of those photopolymerized hydrogel scaffolds in tissue engineering is also discussed. Taken together, it is believed that photopolymerized 3D printing has a great future, whereas conventional 3D printing requires considerable sophistication, and this review can provide readers with a comprehensive approach to developing light-mediated 3D printing for tissue-engineering applications.     

Composite PLA/PEG/nHA/Dexamethasone Scaffold Prepared by 3D Printing for Bone Regeneration

3D printing has become an essential part of bone tissue engineering and attracts great attention for the fabrication of bioactive scaffolds. Combining this rapid manufacturing technique with chemical precipitation, biodegradable 3D scaffold composed of polymer matrix (polylactic acid and polyethylene glycol), ceramics (nano hydroxyapatite), and drugs (dexamethasone (Dex)) is prepared. Results of water contact angle, differential scanning calorimeter, and mechanical tests confirm that incorporation of Dex leads to significantly improved wettability, higher crystallinity degree, and tunable degradation rates. In vitro experiment with mouse MC3T3‐E1 cells implies that Dex released from scaffolds is not beneficial for early cell proliferation, but it improves late alkaline phosphatase secretion and mineralization significantly. Anti‐inflammation assay of murine RAW 264.7 cells proves that Dex released from all the scaffolds successfully suppresses lipopolysaccharide induced interleukin‐6 and inducible nitric oxide synthase secretion by M1 macrophages. Further in vivo experiment on rat calvarial defects indicates that scaffolds containing Dex promote osteoinduction and osteogenic response and would be promising candidates for clinical applications.     

Two‐Photon Polymerization as a Tool for Studying 3D Printed Topography‐Induced Stem Cell Fate

Geometric topographies are known to influence cellular differentiation toward specific phenotypes, but to date the range of features and type of substrates that can be easily fabricated to study these interactions is somewhat limited. In this study, an emerging technology, two‐photon polymerization, is used to print topological patterns with varying feature‐size and thereby study their effect on cellular differentiation. This technique offers rapid manufacturing of topographical surfaces with good feature resolution for shapes smaller than 3 µm. Human‐induced pluripotent stem cells, when attached to these substrates or a non‐patterned control for 1 week, express an array of genetic markers that suggest their differentiation toward a heterogeneous population of multipotent progenitors from all three germ layers. Compared to the topographically smooth control, small features (1.6 µm) encourage differentiation toward ectoderm while large features (8 µm) inhibit self‐renewal. This study demonstrates the potential of using two‐photon polymerization to study and control stem cell fate as a function of substrate interactions. The ability to tailor and strategically design biomaterials in this way can enable more precise and efficient generation or maintenance of desired phenotypes in vitro and in vivo.     

Direct Ink 3D Printing of Porous Carbon Monoliths for Gas Separations

Additive manufacturing or 3D printing is the advanced method of manufacturing monolithic adsorbent materials. Unlike beads or pellets, 3D monolithic adsorbents possess the advantages of widespread structural varieties, low heat and mass transfer resistance, and low channeling of fluids. Despite a large volume of research on 3D printing of adsorbents having been reported, such studies on porous carbons are highly limited. In this work, we have reported direct ink 3D printing of porous carbon; the ink consisted of commercial activated carbon, a gel of poly(4-vinylphenol) and Pluronic F127 as plasticizer, and bentonite as the binder. The 3D printing was performed in a commercial 3D printer that has been extensively modified in the lab. Upon 3D printing and carbonization, the resultant 3D printed porous carbon demonstrated a stable structure with a BET area of 400 m²/g and a total pore volume of 0.27 cm³/g. The isotherms of six pure-component gases, CO₂, CH₄, C₂H₆, N₂, CO, and H₂, were measured on this carbon monolith at 298 K and pressure up to 1 bar. The selectivity of four gas pairs, C₂H₆/CH₄, CH₄/N₂, CO/H₂, and CO₂/N₂, was calculated by Ideally Adsorbed Solution Theory (IAST) and reported. Ten continuous cycles of adsorption and desorption of CO₂ on this carbon confirmed no loss of working capacity of the adsorbent.     

Green Synthesis of Silver Nanoparticles Using Extract of Cilembu Sweet Potatoes (Ipomoea batatas L var. Rancing) as Potential Filler for 3D Printed Electroactive and Anti-Infection Scaffolds

Electroactive biomaterials are fascinating for tissue engineering applications because of their ability to deliver electrical stimulation directly to cells, tissue, and organs. One particularly attractive conductive filler for electroactive biomaterials is silver nanoparticles (AgNPs) because of their high conductivity, antibacterial activity, and ability to promote bone healing. However, production of AgNPs involves a toxic reducing agent which would inhibit biological scaffold performance. This work explores facile and green synthesis of AgNPs using extract of Cilembu sweet potato and studies the effect of baking and precursor concentrations (1, 10 and 100 mM) on AgNPs’ properties. Transmission electron microscope (TEM) results revealed that the smallest particle size of AgNPs (9.95 ± 3.69 nm) with nodular morphology was obtained by utilization of baked extract and ten mM AgNO₃. Polycaprolactone (PCL)/AgNPs scaffolds exhibited several enhancements compared to PCL scaffolds. Compressive strength was six times greater (3.88 ± 0.42 MPa), more hydrophilic (contact angle of 76.8 ± 1.7°), conductive (2.3 ± 0.5 × 10⁻³ S/cm) and exhibited anti-bacterial properties against Staphylococcus aureus ATCC3658 (99.5% reduction of surviving bacteria). Despite the promising results, further investigation on biological assessment is required to obtain comprehensive study of this scaffold. This green synthesis approach together with the use of 3D printing opens a new route to manufacture AgNPs-based electroactive with improved anti-bacterial properties without utilization of any toxic organic solvents.     

丝素蛋白3D打印在生物医学领域中的应用

增材制造,也称为三维(3D)打印,正推动制造、工程、医学等领域的全面创新升级。3D打印技术由于能够个性化定制生物的复杂3D微结构,构建仿生的功能化活组织或人工器官,近十年来在生物医学领域中取得了长足的发展。丝素蛋白(SF)是一种来源丰富、生物可降解、力学性能优良、细胞相容性极佳的天然有机高分子,为3D打印墨水的设计提供了一种有前景的选择。然而,作为结构蛋白,单一组分的SF具有的生理功能有限,且其经过打印后的稳定性较差,限制了SF在3D打印以及生物医药领域中的进一步发展。为此,研究人员通过化学改性技术和先进3D打印技术相结合,使得改性后的SF能够更适用于3D打印,并发展成为一种具有应用价值的生物材料。本文综述了SF的结构特征、SF的化学修饰策略、打印墨水的制备策略以及3D打印SF材料在生物医学领域的最新应用进展,并展望了3D打印SF生物材料的未来发展趋势,为其在更广阔领域的应用提供一定的借鉴。     

3D打印光敏树脂的研究进展

以光敏树脂为原料的立体快速成形3D打印技术,具有成本低、精度高、成型快等优点,在各个领域得到广泛的应用。但是,与之相适应的光敏树脂价格较高,并被国外的一些大公司所垄断,而国内相关研发起步较晚,能够生产和研发性能优良的3D打印光敏树脂的企业较少。简要阐述了3D打印光敏树脂的成形方式、固化原理和组成,重点讨论了配方设计的基本方法和评价指标,并对该领域进行了展望。