Three-dimensional printing of biomaterials for bone tissue engineering: a review

Processing biomaterials into porous scaffolds for bone tissue engineering is a critical and a key step in defining and controlling their physicochemical, mechanical, and biological properties. Biomaterials such as polymers are commonly processed into porous scaffolds using conventional processing techniques, e.g., salt leaching. However, these traditional techniques have shown unavoidable limitations and several shortcomings. For instance, tissue-engineered porous scaffolds with a complex three-dimensional (3D) geometric architecture mimicking the complexity of the extracellular matrix of native tissues and with the ability to fit into irregular tissue defects cannot be produced using the conventional processing techniques. 3D printing has recently emerged as an advanced processing technology that enables the processing of biomaterials into 3D porous scaffolds with highly complex architectures and tunable shapes to precisely fit into irregular and complex tissue defects. 3D printing provides computer-based layer-by-layer additive manufacturing processes of highly precise and complex 3D structures with well-defined porosity and controlled mechanical properties in a highly reproducible manner. Furthermore, 3D printing technology provides an accurate patient-specific tissue defect model and enables the fabrication of a patient-specific tissue-engineered porous scaffold with pre-customized properties.     

Recent Advances on 3D Printing Technique for Thermal‐Related Applications

Advances in ink formulation and printing techniques make producing material systems with new and versatile characteristics and functionalities possible. Additive manufacturing or 3D printing enables fabricating complex structures at a faster production rate using different types of materials for various applications. Recently, 3D printing methods are being studied for thermal‐related applications. In this paper, the authors review recent progress of materials and printing techniques for thermal application devices using composite materials.

     

3D printing of smart materials: A review on recent progresses in 4D printing

ABSTRACT

Additive manufacturing (AM), commonly known as three-dimensional (3D) printing or rapid prototyping, has been introduced since the late 1980s. Although a considerable amount of progress has been made in this field, there is still a lot of research work to be done in order to overcome the various challenges remained. Recently, one of the actively researched areas lies in the additive manufacturing of smart materials and structures. Smart materials are those materials that have the ability to change their shape or properties under the influence of external stimuli. With the introduction of smart materials, the AM-fabricated components are able to alter their shape or properties over time (the 4th dimension) as a response to the applied external stimuli. Hence, this gives rise to a new term called ‘4D printing’ to include the structural reconfiguration over time. In this paper, recent major progresses in 4D printing are reviewed, including 3D printing of enhanced smart nanocomposites, shape memory alloys, shape memory polymers, actuators for soft robotics, self-evolving structures, anti-counterfeiting system, active origami and controlled sequential folding, and some results from our ongoing research. In addition, some research activities on 4D bio-printing are included, followed by discussions on the challenges, applications, research directions and future trends of 4D printing.     

Rapid Open‐Air Digital Light 3D Printing of Thermoplastic Polymer

3D printing has witnessed a new era in which highly complexed customized products become reality. Realizing its ultimate potential requires simultaneous attainment of both printing speed and product versatility. Among various printing techniques, digital light processing (DLP) stands out in its high speed but is limited to intractable light curable thermosets. Thermoplastic polymers, despite their reprocessibility that allows more options for further manipulation, are restricted to intrinsically slow printing methods such as fused deposition modeling. Extending DLP to thermoplastics is highly desirable, but is challenging due to the need to reach rapid liquid–solid separation during the printing process. Here, a successful attempt at DLP printing of thermoplastic polymers is reported, realized by controlling two competing kinetic processes (polymerization and polymer dissolution) simultaneously occurring during printing. With a selected monomer, 4‐acryloylmorpholine (ACMO), printing of thermoplastic 3D scaffolds is demonstrated, which can be further converted into various materials/devices utilizing its unique water‐soluble characteristic. The ultralow viscosity of ACMO, along with surface oxygen inhibition, allows rapid liquid flow toward high‐speed open‐air printing. The process simplicity, enabling mechanism, and material versatility broaden the scope of 3D printing in constructing functional 3D devices including reconfigurable antenna, shape‐shifting structures, and microfluidics.     

Curing characteristics of shape memory polymers in 3D projection and laser stereolithography

The radical shift in 3D printing to fabricate soft active materials such as shape memory polymers (SMPs) has brought along other techniques in realising 4D printing. Stereolithography (SL) process has recently been one of the popular systems for printing SMPs. In this paper, the curing characteristics and behaviour of the SMPs fabricated via projection-type and laser-scanning-type SL process were analysed. Factors such as the UV exposure of the projection type and variation in resin compositions have significant differences in terms of energy density and curing depths when compared to the laser scanning type. Hence, theoretical calculations were made to determine the critical energy density and threshold penetration depth attainable, which enables newly developed SMP materials to be successfully printable using different types of UV-based 3D printing systems.     

Three‐Dimensional Printing of Multifunctional Nanocomposites: Manufacturing Techniques and Applications

The integration of nanotechnology into three‐dimensional printing (3DP) offers huge potential and opportunities for the manufacturing of 3D engineered materials exhibiting optimized properties and multifunctionality. The literature relating to different 3DP techniques used to fabricate 3D structures at the macro‐ and microscale made of nanocomposite materials is reviewed here. The current state‐of‐the‐art fabrication methods, their main characteristics (e.g., resolutions, advantages, limitations), the process parameters, and materials requirements are discussed. A comprehensive review is carried out on the use of metal‐ and carbon‐based nanomaterials incorporated into polymers or hydrogels for the manufacturing of 3D structures, mostly at the microscale, using different 3D‐printing techniques. Several methods, including but not limited to micro‐stereolithography, extrusion‐based direct‐write technologies, inkjet‐printing techniques, and popular powder‐bed technology, are discussed. Various examples of 3D nanocomposite macro‐ and microstructures manufactured using different 3D‐printing technologies for a wide range of domains such as microelectromechanical systems (MEMS), lab‐on‐a‐chip, microfluidics, engineered materials and composites, microelectronics, tissue engineering, and biosystems are reviewed. Parallel advances on materials and techniques are still required in order to employ the full potential of 3D printing of multifunctional nanocomposites.     

Stretchable and Soft Electronics using Liquid Metals

The use of liquid metals based on gallium for soft and stretchable electronics is discussed. This emerging class of electronics is motivated, in part, by the new opportunities that arise from devices that have mechanical properties similar to those encountered in the human experience, such as skin, tissue, textiles, and clothing. These types of electronics (e.g., wearable or implantable electronics, sensors for soft robotics, e‐skin) must operate during deformation. Liquid metals are compelling materials for these applications because, in principle, they are infinitely deformable while retaining metallic conductivity. Liquid metals have been used for stretchable wires and interconnects, reconfigurable antennas, soft sensors, self‐healing circuits, and conformal electrodes. In contrast to Hg, liquid metals based on gallium have low toxicity and essentially no vapor pressure and are therefore considered safe to handle. Whereas most liquids bead up to minimize surface energy, the presence of a surface oxide on these metals makes it possible to pattern them into useful shapes using a variety of techniques, including fluidic injection and 3D printing. In addition to forming excellent conductors, these metals can be used actively to form memory devices, sensors, and diodes that are completely built from soft materials. The properties of these materials, their applications within soft and stretchable electronics, and future opportunities and challenges are considered.     

3D Printing-Assisted Self-Assembly to Bio-Inspired Bouligand Nanostructures

Architected materials with nano/microscale orders can provide superior mechanical properties; however, reproducing such levels of ordering in complex structures has remained challenging. Inspired by Bouligand structures in nature, here, 3D printing of complex geometries with guided long-order radially twisted chiral hierarchy, using cellulose nanocrystals (CNC)-based inks is presented. Detailed rheological measurements, in situ flow analysis, polarized optical microscopy (POM), and director field analysis are employed to evaluate the chiral assembly over the printing process. It is demonstrated that shear flow forces inside the 3D printer's nozzle orient individual CNC particles forming a pseudo-nematic phase that relaxes to uniformly aligned concentric chiral nematic structures after the flow cessation. Acrylamide, a photo-curable monomer, is incorporated to arrest the concentric chiral arrangements within the printed filaments. The time series POM snapshots show that adding the photo-curable monomer at the optimized concentrations does not interfere with chiral self-assemblies and instead increases the chiral relaxation rate. Due to the liquid-like nature of the as-printed inks, optimized Carbopol microgels are used to support printed filaments before photo-polymerization. By paving the path towards developing bio-inspired materials with nanoscale hierarchies in larger-scale printed constructs, this biomimetic approach expands 3D printing materials beyond what has been realized so far.     

Kirigami-Based Light-Induced Shape-Morphing and Locomotion

The development of stimuli-responsive soft actuators, a task largely undertaken by material scientists, has become a major driving force in pushing the frontiers of microrobotics. Devices made of soft active materials are oftentimes small in size, remotely and wirelessly powered/controlled, and capable of adapting themselves to unexpected hurdles. However, nowadays most soft microscale robots are rather simple in terms of design and architecture, and it remains a challenge to create complex 3D soft robots with stimuli-responsive properties. Here, it is suggested that kirigami-based techniques can be useful for fabricating complex 3D robotic structures that can be activated with light. External stress fields introduce out-of-plane deformation of kirigami film actuators made of liquid crystal networks. Such 2D-to-3D structural transformations can give rise to mechanical actuation upon light illumination, thus allowing the realization of kirigami-based light-fuelled robotics. A kirigami rolling robot is demonstrated, where a light beam controls the multigait motion and steers the moving direction in 2D. The device is able to navigate along different routes and moves up a ramp with a slope of 6°. The results demonstrate a facile technique to realize complex and flexible 3D structures with light-activated robotic functions.     

Human-Recombinant-Elastin-Based Bioinks for 3D Bioprinting of Vascularized Soft Tissues

Bioprinting has emerged as an advanced method for fabricating complex 3D tissues. Despite the tremendous potential of 3D bioprinting, there are several drawbacks of current bioinks and printing methodologies that limit  the ability to print elastic and highly vascularized tissues. In particular, fabrication of complex biomimetic structure that are entirely based on 3D bioprinting is still challenging primarily due to the lack of suitable bioinks with high printability, biocompatibility, biomimicry, and proper mechanical properties. To address these shortcomings, in this work the use of recombinant human tropoelastin as a highly biocompatible and elastic bioink for 3D printing of complex soft tissues is demonstrated. As proof of the concept, vascularized cardiac constructs are bioprinted and their functions are assessed in vitro and in vivo. The printed constructs demonstrate endothelium barrier function and spontaneous beating of cardiac muscle cells, which are important functions of cardiac tissue in vivo. Furthermore, the printed construct elicits minimal inflammatory responses, and is shown to be efficiently biodegraded in vivo when implanted subcutaneously in rats. Taken together, these results demonstrate the potential of the elastic bioink for printing 3D functional cardiac tissues, which can eventually be used for cardiac tissue replacement.     

Recent Progress in Biomimetic Additive Manufacturing Technology: From Materials to Functional Structures

Nature has developed high‐performance materials and structures over millions of years of evolution and provides valuable sources of inspiration for the design of next‐generation structural materials, given the variety of excellent mechanical, hydrodynamic, optical, and electrical properties. Biomimicry, by learning from nature's concepts and design principles, is driving a paradigm shift in modern materials science and technology. However, the complicated structural architectures in nature far exceed the capability of traditional design and fabrication technologies, which hinders the progress of biomimetic study and its usage in engineering systems. Additive manufacturing (three‐dimensional (3D) printing) has created new opportunities for manipulating and mimicking the intrinsically multiscale, multimaterial, and multifunctional structures in nature. Here, an overview of recent developments in 3D printing of biomimetic reinforced mechanics, shape changing, and hydrodynamic structures, as well as optical and electrical devices is provided. The inspirations are from various creatures such as nacre, lobster claw, pine cone, flowers, octopus, butterfly wing, fly eye, etc., and various 3D‐printing technologies are discussed. Future opportunities for the development of biomimetic 3D‐printing technology to fabricate next‐generation functional materials and structures in mechanical, electrical, optical, and biomedical engineering are also outlined.     

Multiscale Geometric Design Principles Applied to 3D Printed Schwarzites

Schwartzites are 3D porous solids with periodic minimal surfaces having negative Gaussian curvatures and can possess unusual mechanical and electronic properties. The mechanical behavior of primitive and gyroid schwartzite structures across different length scales is investigated after these geometries are 3D printed at centimeter length scales based on molecular models. Molecular dynamics and finite elements simulations are used to gain further understanding on responses of these complex solids under compressive loads and kinetic impact experiments. The results show that these structures hold great promise as high load bearing and impact‐resistant materials due to a unique layered deformation mechanism that emerges in these architectures during loading. Easily scalable techniques such as 3D printing can be used for exploring mechanical behavior of various predicted complex geometrical shapes to build innovative engineered materials with tunable properties.     

Freeform,Reconfigurable Embedded Printing of All‐Aqueous 3D Architectures

Aqueous microstructures are challenging to create, handle, and preserve since their surfaces tend to shrink into spherical shapes with minimum surface areas. The creation of freeform aqueous architectures will significantly advance the bioprinting of complex tissue‐like constructs, such as arteries, urinary catheters, and tracheae. The generation of complex, freeform, three‐dimensional (3D) all‐liquid architectures using formulated aqueous two‐phase systems (ATPSs) is demonstrated. These all‐liquid microconstructs are formed by printing aqueous bioinks in an immiscible aqueous environment, which functions as a biocompatible support and pregel solution. By exploiting the hydrogen bonding interaction between polymers in ATPS, the printed aqueous‐in‐aqueous reconfigurable 3D architectures can be stabilized for weeks by the noncovalent membrane at the interface. Different cells can be separately combined with compartmentalized bioinks and matrices to obtain tailor‐designed microconstructs with perfusable vascular networks. The freeform, reconfigurable embedded printing of all‐liquid architectures by ATPSs offers unique opportunities and powerful tools since limitless formulations can be designed from among a breadth of natural and synthetic hydrophilic polymers to mimic tissues. This printing approach may be useful to engineer biomimetic, dynamic tissue‐like constructs for potential applications in drug screening, in vitro tissue models, and regenerative medicine.     

Smart polymers and nanocomposites for 3D and 4D printing

Smart materials, also known as intelligent materials, which are responsive to the external stimuli including heat, moisture, stress, pH, and magnetic fields, have found extensive applications in sensors, actuators, soft robots, medical devices and artificial muscles. Using three-dimensional (3D) printing techniques for fabrication of smart devices allows for complex designs and well-controlled manufacturing processes. 4D printing is attributed to the 3D printing of smart materials that can be significantly transformed over time. Herein the smart materials including hydrogels and polymeric nanocomposites used in 4D printing were reviewed and the fundamental mechanisms responsible for the functionalities were discussed in detail. In this report, 4D printing of smart systems and their applications in sensors, actuators and biomedical devices were reviewed to provide a deeper understanding of the current development and the future outlook.     

A New 3D Printing Strategy by Harnessing Deformation,Instability, and Fracture of Viscoelastic Inks

Direct ink writing (DIW) has demonstrated great potential as a multimaterial multifunctional fabrication method in areas as diverse as electronics, structural materials, tissue engineering, and soft robotics. During DIW, viscoelastic inks are extruded out of a 3D printer's nozzle as printed fibers, which are deposited into patterns when the nozzle moves. Hence, the resolution of printed fibers is commonly limited by the nozzle's diameter, and the printed pattern is limited by the motion paths. These limits have severely hampered innovations and applications of DIW 3D printing. Here, a new strategy to exceed the limits of DIW 3D printing by harnessing deformation, instability, and fracture of viscoelastic inks is reported. It is shown that a single nozzle can print fibers with resolution much finer than the nozzle diameter by stretching the extruded ink, and print various thickened or curved patterns with straight nozzle motions by accumulating the ink. A quantitative phase diagram is constructed to rationally select parameters for the new strategy. Further, applications including structures with tunable stiffening, 3D structures with gradient and programmable swelling properties, all printed with a single nozzle are demonstrated. The current work demonstrates that the mechanics of inks plays a critical role in developing 3D printing technology.     

3D打印技术探究

3D打印技术是将三维数字模型分解成若干层平面切片,然后由3D打印机把粉末状、液状或丝状可粘合材料按切片图形逐层叠加,最终堆积成完整物体的技术。文章对3D打印的技术原理、步骤、常用材料、主要技术、发展及建议进行了深层次的探讨。与传统制造技术相比,3D打印技术有很多优势,目前已广泛应用于建筑、工业设计等领域。该技术将会带来全球制造业经济的重大变革。     

Reconfigurable Printed Liquids

Liquids lack the spatial order required for advanced functionality. Interfacial assemblies of colloids, however, can be used to shape liquids into complex, 3D objects, simultaneously forming 2D layers with novel magnetic, plasmonic, or structural properties. Fully exploiting all‐liquid systems that are structured by their interfaces would create a new class of biomimetic, reconfigurable, and responsive materials. Here, printed constructs of water in oil are presented. Both form and function are given to the system by the assembly and jamming of nanoparticle surfactants, formed from the interfacial interaction of nanoparticles and amphiphilic polymers that bear complementary functional groups. These yield dissipative constructs that exhibit a compartmentalized response to chemical cues. Potential applications include biphasic reaction vessels, liquid electronics, novel media for the encapsulation of cells and active matter, and dynamic constructs that both alter, and are altered by, their external environment.     

MXene Printing and Patterned Coating for Device Applications

As a thriving member of the 2D nanomaterials family, MXenes, i.e., transition metal carbides, nitrides, and carbonitrides, exhibit outstanding electrochemical, electronic, optical, and mechanical properties. They have been exploited in many applications including energy storage, electronics, optoelectronics, biomedicine, sensors, and catalysis. Compared to other 2D materials, MXenes possess a unique set of properties such as high metallic conductivity, excellent dispersion quality, negative surface charge, and hydrophilicity, making them particularly suitable as inks for printing applications. Printing and pre/post-patterned coating methods represent a whole range of simple, economically efficient, versatile, and eco-friendly manufacturing techniques for devices based on MXenes. Moreover, printing can allow for complex 3D architectures and multifunctionality that are highly required in various applications. By means of printing and patterned coating, the performance and application range of MXenes can be dramatically increased through careful patterning in three dimensions; thus, printing/coating is not only a device fabrication tool but also an enabling tool for new applications as well as for industrialization.     

Drop-on-demand printing of cells and materials for designer tissue constructs

Adapting bottom-up approaches to tissue engineering is a real challenge. Since the first application of fused deposition modeling for tissue engineering scaffolds, considerable effort has been focused on printing synthetic biodegradable scaffolds. Concurrently a variety of rapid prototyping techniques have been developed to define macroscopically the shapes of deposited biomaterials, including photolithography, syringe-based gel deposition, and solid freeform fabrication. These designed scaffolds have shown promise in regenerating tissues at least equivalent to other scaffolding methods.An exciting advance in scaffold aided tissue regeneration is presented here, that of cell and organ printing, which allows direct printing of cells and proteins within 3D hydrogel structures. Cell printing opens the possibility to programmed deposition of scaffold structure and cell type, thus controlling the type of tissue that can be regenerated within the scaffold. Several examples of printed tissues will be presented including contractile cardiac hybrids. The hybrid materials have properties that can be tailored in 3D to achieve desired porosities, mechanical and chemical properties. The materials include alginate hydrogels with controlled microshell structures that can be built by spraying cross-linkers onto ungelled alginic acid.Endothelial cells were seen to attach to the inside of these microshells. The cells remained viable in constructs as thick as 1 cm due to the programmed porosity. Finite element modeling was used to predict the mechanical properties and to generate CAD models with properties matching cardiac tissue. These results suggest that the printing method could be used for hierarchical design of functional cardiac patches, balanced with porosity for mass transport and structural support.     

Printing Polymer Nanocomposites and Composites in Three Dimensions

Recent advances in materials science and three‐dimensional (3D) printing hold great promises to conceive new classes of multifunctional materials and components for functional devices and products. Various functionalities (e.g., mechanical, electrical, and thermal properties, magnetism) can be offered by the nano‐ and micro‐reinforcements to the non‐functional pure printing materials for the realization of advanced materials and innovative systems. In addition, the ability to print 3D structures in a layer‐by‐layer manner enables manufacturing of highly‐customized complex features and allows an efficient control over the properties of fabricated structures. Here, the authors present a brief overview mainly over the latest progresses in 3D printing of multifunctional polymer nanocomposites and microfiber‐reinforced composites including the benefits, limitations, and potential applications. Only those 3D printing techniques that are compatible with polymer nanocomposites and composites, that is, materials that have already been used as printing materials, are introduced. The very hot topic of 3D printing of thermoplastic composites featuring continuous microfibers is also briefly introduced.