Bio-Design and Manufacturing最新文献

Bioprinting of cell-laden hydrogels is a rapidly growing field in tissue engineering. The advent of digital light processing (DLP) three-dimensional (3D) bioprinting technique has revolutionized the fabrication of complex 3D structures. By adjusting light exposure, it becomes possible to control the mechanical properties of the structure, a critical factor in modulating cell activities. To better mimic cell densities in real tissues, recent progress has been made in achieving high-cell-density (HCD) printing with high resolution. However, regulating the stiffness in HCD constructs remains challenging. The large volume of cells greatly affects the light-based DLP bioprinting by causing light absorption, reflection, and scattering. Here, we introduce a neural network-based machine learning technique to predict the stiffness of cell-laden hydrogel scaffolds. Using comprehensive mechanical testing data from 3D bioprinted samples, the model was trained to deliver accurate predictions. To address the demand of working with precious and costly cell types, we employed various methods to ensure the generalizability of the model, even with limited datasets. We demonstrated a transfer learning method to achieve good performance for a precious cell type with a reduced amount of data. The chosen method outperformed many other machine learning techniques, offering a reliable and efficient solution for stiffness prediction in cell-laden scaffolds. This breakthrough paves the way for the next generation of precision bioprinting and more customized tissue engineering.

Miniature devices comprising stimulus-responsive hydrogels with high environmental adaptability are now considered competitive candidates in the fields of biomedicine, precise sensors, and tunable optics. Reliable and advanced fabrication methods are critical for maximizing the application capabilities of miniature devices. Light-based three-dimensional (3D) printing technology offers the advantages of a wide range of applicable materials, high processing accuracy, and strong 3D fabrication capability, which is suitable for the development of miniature devices with various functions. This paper summarizes and highlights the recent advances in light-based 3D-printed miniaturized devices, with a focus on the latest breakthroughs in light-based fabrication technologies, smart stimulus-responsive hydrogels, and tunable miniature devices for the fields of miniature cargo manipulation, targeted drug and cell delivery, active scaffolds, environmental sensing, and optical imaging. Finally, the challenges in the transition of tunable miniaturized devices from the laboratory to practical engineering applications are presented. Future opportunities that will promote the development of tunable microdevices are elaborated, contributing to their improved understanding of these miniature devices and further realizing their practical applications in various fields.

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Increasing evidence indicates that engineered nerve grafts have great potential for the regeneration of peripheral nerve injuries (PNIs). While most studies have focused only on the topographical features of the grafts, we have considered both the biophysical and biochemical manipulations in our applied nanoscaffold. To achieve this, we fabricated an electrospun nanofibrous scaffold (ENS) containing polylactide nanofibers loaded with lithium (Li) ions, a Wnt/β‐catenin signaling activator. In addition, we seeded human adipose-derived mesenchymal stem cells (hADMSCs) onto this engineered scaffold to examine if their differentiation toward Schwann-like cells was induced. We further examined the efficacy of the scaffolds for nerve regeneration in vivo via grafting in a PNI rat model. Our results showed that Li-loaded ENSs gradually released Li within 11 d, at concentrations ranging from 0.02 to (3.64 ± 0.10) mmol/L, and upregulated the expression of Wnt/β-catenin target genes (cyclinD1 and c-Myc) as well as those of Schwann cell markers (growth-associated protein 43 (GAP43), S100 calcium binding protein B (S100B), glial fibrillary acidic protein (GFAP), and SRY-box transcription factor 10 (SOX10)) in differentiated hADMSCs. In the PNI rat model, implantation of Li-loaded ENSs with/without cells improved behavioral features such as sensory and motor functions as well as the electrophysiological characteristics of the injured nerve. This improved function was further validated by histological analysis of sciatic nerves grafted with Li-loaded ENSs, which showed no fibrous connective tissue but enhanced organized myelinated axons. The potential of Li-loaded ENSs in promoting Schwann cell differentiation of hADMSCs and axonal regeneration of injured sciatic nerves suggests their potential for application in peripheral nerve tissue engineering.

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Mandibular advancement devices (MADs) are widely used treatments for obstructive sleep apnea. MADs function by advancing the lower jaw to open the upper airway. To increase patient comfort, most patients allow the mouth to be opened. However, not all systems maintain the lower jaw in a forward position during mouth opening, which results in the production of a retrusion that favors the collapse of the upper airway. Furthermore, the kinematic behavior of the mechanism formed by the mandible-device assembly depends on jaw morphology. This means that, during mouth opening, some devices cause lower jaw protrusion in some patients, but cause its retraction in others. In this study, we report the behavior of well-known devices currently on the market. To do so, we developed a kinematic model of the lower jaw device assembly. This model was validated for all devices analyzed using a high-resolution camera system. Our results show that some of the devices analyzed here did not produce the correct behavior during patient mouth opening.

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Nerve regeneration holds significant potential in the treatment of various skeletal and neurological disorders to restore lost sensory and motor functions. The potential of nerve regeneration in ameliorating neurological diseases and injuries is critical to human health. Three-dimensional (3D) printing offers versatility and precision in the fabrication of neural scaffolds. Complex neural structures such as neural tubes and scaffolds can be fabricated via 3D printing. This review comprehensively analyzes the current state of 3D-printed neural scaffolds and explores strategies to enhance their design. It highlights therapeutic strategies and structural design involving neural materials and stem cells. First, nerve regeneration materials and their fabrication techniques are outlined. The applications of conductive materials in neural scaffolds are reviewed, and their potential to facilitate neural signal transmission and regeneration is highlighted. Second, the progress in 3D-printed neural scaffolds applied to the peripheral and central nerves is comprehensively evaluated, and their potential to restore neural function and promote the recovery of different nervous systems is emphasized. In addition, various applications of 3D-printed neural scaffolds in peripheral and neurological diseases, as well as the design strategies of multifunctional biomimetic scaffolds, are discussed.

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Intracellular electrophysiological research is vital for biological and medical research. Traditional planar microelectrode arrays (MEAs) have disadvantages in recording intracellular action potentials due to the loose cell–electrode interface. To investigate intracellular electrophysiological signals with high sensitivity, electroporation was used to obtain intracellular recordings. In this study, a biosensing system based on a nanoporous electrode array (NPEA) integrating electrical perforation and signal acquisition was established to dynamically and sensitively record the intracellular potential of cardiomyocytes over a long period of time. Moreover, nanoporous electrodes can induce the protrusion of cell membranes and enhance cell–electrode interfacial coupling, thereby facilitating effective electroporation. Electrophysiological signals over the entire recording process can be quantitatively and segmentally analyzed according to the signal changes, which can equivalently reflect the dynamic evolution of the electroporated cardiomyocyte membrane. We believe that the low-cost and high-performance nanoporous biosensing platform suggested in this study can dynamically record intracellular action potential, evaluate cardiomyocyte electroporation, and provide a new strategy for investigating cardiology pharmacological science.

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Paper-based microchips have different advantages, such as better biocompatibility, simple production, and easy handling, making them promising candidates for clinical diagnosis and other fields. This study describes a method developed to fabricate modular three-dimensional (3D) paper-based microfluidic chips based on projection-based 3D printing (PBP) technology. A series of two-dimensional (2D) paper-based microfluidic modules was designed and fabricated. After evaluating the effect of exposure time on the accuracy of the flow channel, the resolution of this channel was experimentally analyzed. Furthermore, several 3D paper-based microfluidic chips were assembled based on the 2D ones using different methods, with good channel connectivity. Scaffold-based 2D and hydrogel-based 3D cell culture systems based on 3D paper-based microfluidic chips were verified to be feasible. Furthermore, by combining extrusion 3D bioprinting technology and the proposed 3D paper-based microfluidic chips, multiorgan microfluidic chips were established by directly printing 3D hydrogel structures on 3D paper-based microfluidic chips, confirming that the prepared modular 3D paper-based microfluidic chip is potentially applicable in various biomedical applications.

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Integrated printing of magnetic soft robots with complex structures using recyclable materials to achieve sustainability of the soft robots remains a persistent challenge. Here, we propose a kind of ferromagnetic fibers that can be used to print soft robots with complex structures. These ferromagnetic fibers are recyclable and can make soft robots sustainable. The ferromagnetic fibers based on thermoplastic polyurethane (TPU)/NdFeB hybrid particles are extruded by an extruder. We use a desktop three-dimensional (3D) printer to demonstrate the feasibility of printing two-dimensional (2D) and complex 3D soft robots. These printed soft robots can be recycled and reprinted into new robots once their tasks are completed. Moreover, these robots show almost no difference in actuation capability compared to prior versions and have new functions. Successful applications include lifting, grasping, and moving objects, and these functions can be operated untethered wirelessly. In addition, the locomotion of the magnetic soft robot in a human stomach model shows the prospect of medical applications. Overall, these fully recyclable ferromagnetic fibers pave the way for printing and reprinting sustainable soft robots while also effectively reducing e-waste and robotics waste materials, which is important for resource conservation and environmental protection.

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Polycaprolactone (PCL) scaffolds that are produced through additive manufacturing are one of the most researched bone tissue engineering structures in the field. Due to the intrinsic limitations of PCL, carbon nanomaterials are often investigated to reinforce the PCL scaffolds. Despite several studies that have been conducted on carbon nanomaterials, such as graphene (G) and graphene oxide (GO), certain challenges remain in terms of the precise design of the biological and nonbiological properties of the scaffolds. This paper addresses this limitation by investigating both the nonbiological (element composition, surface, degradation, and thermal and mechanical properties) and biological characteristics of carbon nanomaterial-reinforced PCL scaffolds for bone tissue engineering applications. Results showed that the incorporation of G and GO increased surface properties (reduced modulus and wettability), material crystallinity, crystallization temperature, and degradation rate. However, the variations in compressive modulus, strength, surface hardness, and cell metabolic activity strongly depended on the type of reinforcement. Finally, a series of phenomenological models were developed based on experimental results to describe the variations of scaffold’s weight, fiber diameter, porosity, and mechanical properties as functions of degradation time and carbon nanomaterial concentrations. The results presented in this paper enable the design of three-dimensional (3D) bone scaffolds with tuned properties by adjusting the type and concentration of different functional fillers.

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The plausibility of human exposure to particulate matter (PM) has witnessed an increase within the last several years. PM of different sizes has been discovered in the atmosphere given the role of dust transport in weather and climate composition. As a regulator, the lung epithelium orchestrates the innate response to local damage. Herein, we developed a lung epithelium-on-a-chip platform consisting of easily moldable polydimethylsiloxane layers along with a thin, flexible, and transparent ionic liquid-based poly(hydroxyethyl) methacrylate gel membrane. The epithelium was formed through the culture of human lung epithelial cells (Calu-3) on this membrane. The mechanical stress at the air–liquid interface during inhalation/exhalation was recapitulated using an Arduino-based servo motor system, which applied a uniaxial tensile strength from the two sides of the chip with 10% strain and a frequency of 0.2 Hz. Subsequently, the administration of silica nanoparticles (PM0.5) with an average size of 463 nm to the on-chip platform under static, dynamic, and dynamic + mechanical stress (DMS) conditions demonstrated the effect of environmental pollutants on lung epithelium. The viability and release of lactate dehydrogenase were determined along with proinflammatory response through the quantification of tumor necrosis factor-α, which indicated alterations in the epithelium.

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