Consecutive multimaterial printing of biomimetic ionic hydrogel power sources with high flexibility and stretchability.

Electric eel is an excellent example to harness ion-concentration gradients for sustainable power generation. However, current strategies to create electric-eel-inspired power sources commonly involve manual stacking of multiple salinity-gradient power source units, resulting in low efficiency, unstable contact, and poor flexibility. Here we propose a consecutive multimaterial printing strategy to efficiently fabricate biomimetic ionic hydrogel power sources with a maximum stretchability of 137%. The consecutively-printed ionic hydrogel power source filaments showed seamless bonding interface and can maintain stable voltage outputs for 1000 stretching cycles at 100% strain. With arrayed multi-channel printhead, power sources with a maximum voltage of 208 V can be automatically printed and assembled in parallel within 30 min. The as-printed flexible power source filaments can be woven into a wristband to power a digital wristwatch. The presented strategy provides a tool to efficiently produce electric-eel-inspired ionic hydrogel power sources with great stretchability for various flexible power source applications.

[Development and Challenges of Additive Manufactured Customized Implant].

Additive manufacturing (3D printing) technology aligns with the direction of precision and customization in future medicine, presenting a significant opportunity for innovative development in high-end medical devices. Currently, research and industrialization of 3D printed medical devices mainly focus on nondegradable implants and degradable implants. Primary areas including metallic orthopaedic implants, polyether-ether-ketone (PEEK) bone implants, and biodegradable implants have been developed for clinical and industrial application. Recent research achievements in these areas are reviewed, with a discussion on the additive manufacturing technologies and applications for customized implants. Challenges faced by different types of implants are analyzed from technological, application, and regulatory perspectives. Furthermore, prospects and suggestions for future development are outlined.

Multimaterial Printing of Serpentine Microarchitectures with Synergistic Mechanical/Piezoelectric Stimulation for Enhanced Cardiac-Specific Functional Regeneration.

Recreating the natural heart's mechanical and electrical environment is crucial for engineering functional cardiac tissue and repairing infarcted myocardium in vivo. In this study, multimaterial-printed serpentine microarchitectures are presented with synergistic mechanical/piezoelectric stimulation, incorporating polycaprolactone (PCL) microfibers for mechanical support, polyvinylidene fluoride (PVDF) microfibers for piezoelectric stimulation, and magnetic PCL/Fe3O4 for controlled deformation via an external magnet. Rat cardiomyocytes in piezoelectric constructs, subjected to dynamic mechanical stimulation, exhibit advanced maturation, featuring superior sarcomeric structures, improved calcium transients, and upregulated maturation genes compared to non-piezoelectric constructs. Furthermore, these engineered piezoelectric cardiac constructs demonstrate significant structural and functional repair of infarcted myocardium, as evidenced by enhanced ejection and shortening fraction, reduced fibrosis and inflammation, and increased angiogenesis. The findings underscore the therapeutic potential of piezoelectric cardiac constructs for myocardial infarction therapy.

Biotribological properties of 3D printed high-oriented short carbon fiber reinforced polymer composites for artificial joints.

Short carbon fiber (SCF) reinforced polymer composites are expected to possess outstanding biotribological and mechanical properties in certain direction, while the non-oriented SCF weakens its reinforcing effect in the matrix. In this work, high-oriented SCF was achieved during nozzle extrusion, and then SCF reinforced polyether-ether-ketone (PEEK) composites were fabricated by fused deposition modeling (FDM). The concrete orientation process of SCF was theoretically simulated, and significant shear stress difference was generated at both ends of SCF. As a result, the SCF was distributed in the matrix in a hierarchical structure, containing surface layer I, II and core layer. Moreover, the SCF was oriented highly along the printing direction and demonstrated a more competitive orientation distribution compared to other studies. The SCF/PEEK composites showed a considerable improvement in wear resistance by 44 % due to self-lubricating and load-bearing capability of SCF. Besides, it demonstrated enhancements in Brinell hardness, compressive and impact strength by 48.52 %, 16.42 % and 53.64 %, respectively. In addition, SCF/PEEK composites also showed good cytocompatibility. The findings gained herein are useful for developing the high-oriented SCF reinforced polymer composites with superior biotribological and mechanical properties for artificial joints.

Microphysiological systems inspired by leaf venation.

Nature-inspired microfluidic networks are revolutionizing microphysiological systems, allowing for the precise emulation of human physiology. This article delves into the fabrication techniques of leaf-venation-inspired (LVI) microfluidic networks and explores their transformative applications in organ-on-a-chip and tissue engineering, showcasing their pivotal role in advancing biomedical research.

Outcomes following the excision of sarcoma and chest wall reconstruction using 3D printed implant.

The survival outcomes of patients with chest wall sarcomas (CWS) were evaluated after receiving wide excision and chest wall reconstruction by using three-dimensional printed (3DP) implants. The survival outcomes evaluating the effect of 3DP implants for chest wall reconstruction is lacking. Here, forty-nine patients with CWS underwent radical wide excision and chest wall reconstruction using 3DP implants. The surgical data and long-term survival outcomes were collected and analyzed. With a median follow-up of 36 months, the disease-free survival (DFS) and overall survival (OS) were 31.7% and 58.5%, respectively. In addition, the 3-year DFS and OS can be significantly differentiated using the classification criteria of tumor grade, tumor size tumor area. Hence, wide excision and chest wall reconstruction using three-dimensional printed implants are a safe and effective treatment for chest wall sarcoma. The novel classification criteria of tumor size and area have the potential to predict the prognosis of CWS.

Heart-on-a-chip systems with tissue-specific functionalities for physiological, pathological, and pharmacological studies.

Recent advances in heart-on-a-chip systems hold great promise to facilitate cardiac physiological, pathological, and pharmacological studies. This review focuses on the development of heart-on-a-chip systems with tissue-specific functionalities. For one thing, the strategies for developing cardiac microtissues on heart-on-a-chip systems that closely mimic the structures and behaviors of the native heart are analyzed, including the imitation of cardiac structural and functional characteristics. For another, the development of techniques for real-time monitoring of biophysical and biochemical signals from cardiac microtissues on heart-on-a-chip systems is introduced, incorporating cardiac electrophysiological signals, contractile activity, and biomarkers. Furthermore, the applications of heart-on-a-chip systems in intelligent cardiac studies are discussed regarding physiological/pathological research and pharmacological assessment. Finally, the future development of heart-on-a-chip toward a higher level of systematization, integration, and maturation is proposed.

Mechanical Metamaterials for Handwritten Digits Recognition.

The increasing needs for new types of computing lie in the requirements in harsh environments. In this study, the successful development of a non-electrical neural network is presented that functions based on mechanical computing. By overcoming the challenges of low mechanical signal transmission efficiency and intricate layout design methodologies, a mechanical neural network based on bistable kirigami-based mechanical metamaterials have designed. In preliminary tests, the system exhibits high reliability in recognizing handwritten digits and proves operable in low-temperature environments. This work paves the way for a new, alternative computing system with broad applications in areas where electricity is not accessible. By integrating with the traditional electronic computers, the present system lays the foundation for a more diversified form of computing.

Coaxial Electrohydrodynamic Printing of Microscale Core-Shell Conductive Features for Integrated Fabrication of Flexible Transparent Electronics.

Reliable insulation of microscale conductive features is required to fabricate functional multilayer circuits or flexible electronics for providing specific physical/chemical/electrical protection. However, the existing strategies commonly rely on manual assembling processes or multiple microfabrication processes, which is time-consuming and a great challenge for the fabrication of flexible transparent electronics with microscale features and ultrathin thickness. Here, we present a novel coaxial electrohydrodynamic (CEHD) printing strategy for the one-step fabrication of microscale flexible electronics with conductive materials at the core and insulating material at the outer layer. A finite element analysis (FEA) method is established to simulate the CEHD printing process. The extrusion sequence of the conductive and insulating materials during the CEHD printing process shows little effect on the morphology of the core-shell filaments, which can be achieved on different flexible substrates with a minimum conductive line width of 32 ± 3.2 µm, a total thickness of 53.6 ± 4.8 µm, and a conductivity of 0.23 × 107 S/m. The thin insulating layer can provide the inner conductive filament enough protection in 3D, which endows the resultant microscale core-shell electronics with good electrical stability when working in different chemical solvent solutions or under large deformation conditions. Moreover, the presented CEHD printing strategy offers a unique capability to sequentially fabricate an insulating layer, core-shell conductive pattern, and exposed electrodes by simply controlling the material extrusion sequence. The resultant large-area transparent electronics with two-layer core-shell patterns exhibit a high transmittance of 98% and excellent electrothermal performance. The CEHD-printed flexible microelectrode array is successfully used to record the electrical signals of beating mouse hearts. It can also be used to fabricate large-area flexible capacitive sensors to accurately measure the periodical pressure force. We envision that the present CEHD printing strategy can provide a promising tool to fabricate complex three-dimensional electronics with microscale resolution, high flexibility, and multiple functionalities.

Microstructure Optimization for Design of Porous Tantalum Scaffolds Based on Mechanical Properties and Permeability.

Porous tantalum (Ta) implants have important clinical application prospects due to their appropriate elastic modulus, and their excellent bone growth and bone conduction ability. However, porous Ta microstructure designs generally mimic titanium (Ti) implants commonly used in the clinic, and there is a lack of research on the influence of the microstructure on the mechanical properties and penetration characteristics, which will greatly affect bone integration performance. This study explored the effects of different microstructure parameters, including the fillet radius of the middle plane and top planes, on the mechanics and permeability properties of porous Ta diamond cells through simulation, and put forward an optimization design with a 0.5 mm midplane fillet radius and 0.3 mm top-plane fillet radius in order to significantly decrease the stress concentration effect and improve permeability. On this basis, the porous Ta structures were prepared by Laser Powder Bed Fusion (LPBF) technology and evaluated before and after microstructural optimization. The elastic modulus and the yield strength were increased by 2.31% and 10.39%, respectively. At the same time, the permeability of the optimized structure was also increased by 8.25%. The optimized microstructure design of porous Ta has important medical application value.

Impact Resistance of 3D-Printed Continuous Hybrid Fiber-Reinforced Composites.

Improving the resilience of 3D-printed composites through material extrusion technology (MEX) is an ongoing challenge in order to meet the rigorous requirements of critical applications. The primary objective of this research was to enhance the impact resistance of 3D-printed composites by incorporating continuous hybrid fibers. Herein, continuous virgin carbon (1k) and Kevlar (130D and 200D) fibers were used with different weight and volume fractions as reinforcing fibers to produce hybrid and non-hybrid composites for impact resistance testing to obtain energy absorption with different impact energies: 20 J, 30 J, 40 J, and 50 J. Moreover, 0°/90° fiber orientations were used. Hybrid composites with combinations of PLA + CF + 130D KF and PLA + CF + 200D KF showed higher impact resistance, less damaged areas (71.45% to 90.486%), and higher energy absorption (5.52-11.64% more) behaviors compared to PLA + CF non-hybrids. CT scan images provided strong evidence to resist the fracture and breakage patterns, because the stiffness and elongation properties of the fibers acted together in the hybrids specimens. Furthermore, positive hybrid effects of the PLA + CF + KF hybrids also showed an ideal match of toughness and flexibility in order to resist the impacts. In the future, these hybrids will have the potential to replace the single type of composites in the fields of aerospace and automobiles.

Spatial 3D Printing of Continuous Fiber-Reinforced Composite Multilayer Truss Structures with Controllable Structural Performance.

Continuous fiber-reinforced composite truss structures have broad application prospects in aerospace engineering owing to their high structural bearing efficiency and multifunctional applications. This paper presents the design and fabrication of multilayer truss structures with controlled mechanical properties based on continuous fiber-reinforced thermoplastic composite 3D printing. Continuous fiber composite pyramid trusses fabricated by 3D printing have high specific stiffness and strength, with maximum equivalent compression modulus and strength of 401.91 MPa and 30.26 MPa, respectively. Moreover, the relative density of a truss structure can be as low as 1.45%. Additionally, structural units can be extended in any direction to form a multilayer truss structure. Structural performance can be controlled by designing the parameters of each layer. This study offers a novel approach for designing a multifunctional multilayer truss structure, a structure with low-density needs and unique load-bearing effects.

Advancing Intelligent Organ-on-a-Chip Systems with Comprehensive In Situ Bioanalysis.

In vitro models are essential to a broad range of biomedical research, such as pathological studies, drug development, and personalized medicine. As a potentially transformative paradigm for 3D in vitro models, organ-on-a-chip (OOC) technology has been extensively developed to recapitulate sophisticated architectures and dynamic microenvironments of human organs by applying the principles of life sciences and leveraging micro- and nanoscale engineering capabilities. A pivotal function of OOC devices is to support multifaceted and timely characterization of cultured cells and their microenvironments. However, in-depth analysis of OOC models typically requires biomedical assay procedures that are labor-intensive and interruptive. Herein, the latest advances toward intelligent OOC (iOOC) systems, where sensors integrated with OOC devices continuously report cellular and microenvironmental information for comprehensive in situ bioanalysis, are examined. It is proposed that the multimodal data in iOOC systems can support closed-loop control of the in vitro models and offer holistic biomedical insights for diverse applications. Essential techniques for establishing iOOC systems are surveyed, encompassing in situ sensing, data processing, and dynamic modulation. Eventually, the future development of iOOC systems featuring cross-disciplinary strategies is discussed.

Pore size-mediated macrophage M1 to M2 transition affects osseointegration of 3D-printed PEEK scaffolds.

Increasing evidence indicates that macrophages play an important role in angiogenesis and bone regeneration. Because the phenotypic polarization of macrophage is extremely sensitive to the pore size of materials, poly(ether-ether-ketone) (PEEK) scaffolds with pore sizes of 0, 200, and 400 µm were prepared, and the influence of pore size-mediated macrophage polarization on subsequent angiogenesis and osteogenesis was examined. The interaction results of macrophages and scaffolds indicated that macrophages were responsive to the pore size of three-dimensional (3D)-printed PEEK scaffolds, and large pore size scaffolds showed greater potential in inducing M1 to M2 transition of macrophage and enhanced macrophage secretion of high concentrations of osteogenesis-related and angiogenesis-related cytokines. When human umbilical vein endothelial cells (HUVECs) and bone marrow mesenchymal stem cells (BMSCs) were cultured in the conditioned medium derived from co-culture of macrophages and scaffolds, HUVECs showed good angiogenic responses in terms of cell migration and angiogenic gene expression, while BMSCs showed good osteogenic differentiation effect in in vitro mineralization and osteogenesis-related gene expression. The results of bone defect repair showed that the bone volume/total volume ratio and trabecular thickness of the large pore size PEEK scaffold were significantly higher, and it had better biomechanical properties and achieved a better osseointegration effect. Our data demonstrate that large-pore PEEK scaffolds promote angiogenesis and osteogenic differentiation in vitro and osseointegration in vivo, most likely because scaffolds with larger pore size are able to mediate a higher degree of M1 to M2 transition in macrophages.

Programmable spatial deformation by controllable off-center freestanding 4D printing of continuous fiber reinforced liquid crystal elastomer composites.

Owing to their high deformation ability, 4D printed structures have various applications in origami structures, soft robotics and deployable mechanisms. As a material with programmable molecular chain orientation, liquid crystal elastomer is expected to produce the freestanding, bearable and deformable three-dimensional structure. However, majority of the existing 4D printing methods for liquid crystal elastomers can only fabricate planar structures, which limits their deformation designability and bearing capacity. Here we propose a direct ink writing based 4D printing method for freestanding continuous fiber reinforced composites. Continuous fibers can support freestanding structures during the printing process and improve the mechanical property and deformation ability of 4D printed structures. In this paper, the integration of 4D printed structures with fully impregnated composite interfaces, programmable deformation ability and high bearing capacity are realized by adjusting the off-center distribution of the fibers, and the printed liquid crystal composite can carry a load of up to 2805 times its own weight and achieve a bending deformation curvature of 0.33 mm-1 at 150 °C. This research is expected to open new avenues for creating soft robotics, mechanical metamaterials and artificial muscles.

Biomimetic three-dimensional glioma model printed in vitro for the studies of glioma cells and neurons interactions.

1The interactions between glioma cells and neurons are important for glioma progression but are rarely mimicked and recapitulated in in vitro three-dimensional (3D) models, which may affect the success rate of relevant drug research and development. In this study, an in vitro bioprinted 3D glioma model consisting of an outer hemispherical shell with neurons and an inner hemisphere with glioma cells is proposed to simulate the natural glioma. This model was produced by extrusion-based 3D bioprinting technology. The cells survival rate, morphology, and intercellular Ca2+ concentration studies were carried out up to 5 days of culturing. It was found that neurons could promote the proliferation of glioma cells around them, associate the morphological changes of glioma cells to be neuron-like, and increase the expression of intracellular Ca2+ of glioma cells. Conversely, the presence of glioma cells could maintain the neuronal survival rate and promote the neurite outgrowth. The results indicated that glioma cells and neurons facilitated each other implying a symbiotic pattern established between two types of cells during the early stage of glioma development, which were seldom found in the present artificial glioma models. The proposed bioprinted glioma model can mimic the natural microenvironment of glioma tissue, provide an in-depth understanding of cell-cell interactions, and enable pathological and pharmacological studies of glioma.

3D Bioprinting of Neurovascular Tissue Modeling with Collagen-Based Low-Viscosity Composites.

In vitro neurovascular unit (NVU) models are valuable for investigating brain functions and developing drugs. However, it remains challenging to recapitulate the native architectural features and ultra-soft extracellular matrix (ECM) properties of the natural NVU. Cell-laden bioprinting is promising to prepare complex living tissues, but hard to balance the fidelity and cell growth. This study proposes a novel two-stage methodology for biomanufacturing functional 3D neurovascular constructs in vitro with low modulus of ECM. At the shaping stage, a low-viscosity alginate/collagen is printed through an embedded approach; at the culturing stage, the alginate is removed through targeted lysing. The low-viscosity and rapid crosslinking properties provide a printing resolution of ≈10 µm, and the lysis processing can decrease the hydrogels' modulus to ≈1 kPa and adjust the porosity of the microstructure, providing cells with an environment closing to the brain ECM. A 3D hollow coaxial neurovascular model is fabricated, in which the endothelial cells has expressed tight junction proteins and shown selective permeability, and the astrocytes outside of the endothelial layer are found to spread out with branches and directly interact with endothelial cells. The present study offers a promising modeling method for better understanding the NVU function and screening neuro-drugs.

Development of Electro-Conductive Composite Bioinks for Electrohydrodynamic Bioprinting with Microscale Resolution.

Bioprinting has attracted extensive attention in the field of tissue engineering due to its unique capability in constructing biomimetic tissue constructs in a highly controlled manner. However, it is still challenging to reproduce the physical and structural properties of native electroactive tissues due to the poor electroconductivity of current bioink systems as well as the limited printing resolution of conventional bioprinting techniques. In this work, an electro-conductive hydrogel is prepared by introducing poly (3,4-ethylene dioxythiophene): poly (styrene sulfonate) (PEDOT: PSS) into an RGD (GGGGRGDSP)-functionalized alginate and fibrin system (RAF), and then electrohydrodynamic (EHD)-bioprinted to form living tissue constructs with microscale resolution. The addition of 0.1 (w/v%) PEDOT: PSS increases the electroconductivity to 1.95 ± 0.21 S m-1 and simultaneously has little effect on cell viability. Compared with pure RAF bioink, the presence of PEDOT: PSS expands the printable parameters for EHD-bioprinting, and hydrogel filaments with the smallest feature size of 48.91 ± 3.44 µm can be obtained by further optimizing process parameters. Furthermore, the EHD-bioprinted electro-conductive living tissue constructs with improved resolution show good viability (>85%). The synergy of the advanced electro-conductive hydrogel and EHD-bioprinting presented here may provide a promising approach for engineering electro-conductive and cell-laden constructs for electroactive tissue engineering.

Leaf-venation-directed cellular alignment for macroscale cardiac constructs with tissue-like functionalities.

Recapitulating the complex structural, mechanical, and electrophysiological properties of native myocardium is crucial to engineering functional cardiac tissues. Here, we report a leaf-venation-directed strategy that enables the compaction and remodeling of cell-hydrogel hybrids into highly aligned and densely packed organizations in predetermined patterns. This strategy contributes to interconnected tubular structures with cell alignment along the hierarchical channels. Compared to randomly-distributed cells, the engineered leaf-venation-directed-cardiac tissues from neonatal rat cardiomyocytes manifest advanced maturation and functionality as evidenced by detectable electrophysiological activity, macroscopically synchronous contractions, and upregulated maturation genes. As a demonstration, human induced pluripotent stem cell-derived leaf-venation-directed-cardiac tissues are engineered with evident structural and functional improvement over time. With the elastic scaffolds, leaf-venation-directed tissues are assembled into 3D centimeter-scale cardiac constructs with programmed mechanical properties, which can be delivered through tubing without affecting cell viability. The present strategy may generate cardiac constructs with multifaceted functionalities to meet clinical demands.

Additively manufactured polyether ether ketone (PEEK) skull implant as an alternative to titanium mesh in cranioplasty.

173Cranioplasty is used for skull defects, involving lifting the scalp and restoring the contour of the skull with the original skull piece, titanium mesh, or solid biomaterial. Additive manufacturing (AM) technology, known as three-dimensional (3D) printing, is now utilized by medical professionals to develop customized replicas of tissues, organs and bones, offering a valid option with perfect anatomic fitting in the individual and skeletal reconstruction. Here, we report a case that underwent titanium mesh cranioplasty 15 years ago. The poor appearance of the titanium mesh weakened the left eyebrow arch and resulted in the formation of a sinus tract. Cranioplasty was performed using an additively manufactured polyether ether ketone (PEEK) skull implant. PEEK skull implants have been successfully implanted without any complications. To our knowledge, this is the first reported case of direct use of fused filament fabrication (FFF)-fabricated PEEK implant for cranial repair. The FFF-printed PEEK customized skull implant could possess simultaneously with adjustable material thickness and more complex structure, tunable mechanical properties, and low processing costs compared with traditional manufacturing processes. While meeting clinical needs, this production method is an appropriate alternative for promoting the use of PEEK materials in cranioplasty.