Additive manufacturing and three-dimensional printing in obstetrics and gynecology: a comprehensive review.

Three-dimensional (3D) printing, also known as additive manufacturing, is a technology used to create complex 3D structures out of a digital model that can be almost any shape. Additive manufacturing allows the creation of customized, finely detailed constructs. Improvements in 3D printing, increased 3D printer availability, decreasing costs, development of biomaterials, and improved cell culture techniques have enabled complex, novel, and customized medical applications to develop. There have been rapid development and utilization of 3D printing technologies in orthopedics, dentistry, urology, reconstructive surgery, and other health care areas. Obstetrics and Gynecology (OBGYN) is an emerging application field for 3D printing. This technology can be utilized in OBGYN for preventive medicine, early diagnosis, and timely treatment of women-and-fetus-specific health issues. Moreover, 3D printed simulations of surgical procedures enable the training of physicians according to the needs of any given procedure. Herein, we summarize the technology and materials behind additive manufacturing and review the most recent advancements in the application of 3D printing in OBGYN studies, such as diagnosis, surgical planning, training, simulation, and customized prosthesis. Furthermore, we aim to give a future perspective on the integration of 3D printing and OBGYN applications and to provide insight into the potential applications.

3D-printed microrobots from design to translation.

Microrobots have attracted the attention of scientists owing to their unique features to accomplish tasks in hard-to-reach sites in the human body. Microrobots can be precisely actuated and maneuvered individually or in a swarm for cargo delivery, sampling, surgery, and imaging applications. In addition, microrobots have found applications in the environmental sector (e.g., water treatment). Besides, recent advancements of three-dimensional (3D) printers have enabled the high-resolution fabrication of microrobots with a faster design-production turnaround time for users with limited micromanufacturing skills. Here, the latest end applications of 3D printed microrobots are reviewed (ranging from environmental to biomedical applications) along with a brief discussion over the feasible actuation methods (e.g., on- and off-board), and practical 3D printing technologies for microrobot fabrication. In addition, as a future perspective, we discussed the potential advantages of integration of microrobots with smart materials, and conceivable benefits of implementation of artificial intelligence (AI), as well as physical intelligence (PI). Moreover, in order to facilitate bench-to-bedside translation of microrobots, current challenges impeding clinical translation of microrobots are elaborated, including entry obstacles (e.g., immune system attacks) and cumbersome standard test procedures to ensure biocompatibility.

Biomedical optical fibers.

Optical fibers with the ability to propagate and transfer data via optical signals have been used for decades in medicine. Biomaterials featuring the properties of softness, biocompatibility, and biodegradability enable the introduction of optical fibers' uses in biomedical engineering applications such as medical implants and health monitoring systems. Here, we review the emerging medical and health-field applications of optical fibers, illustrating the new wave for the fabrication of implantable devices, wearable sensors, and photodetection and therapy setups. A glimpse of fabrication methods is also provided, with the introduction of 3D printing as an emerging fabrication technology. The use of artificial intelligence for solving issues such as data analysis and outcome prediction is also discussed, paving the way for the new optical treatments for human health.

Assessing reusability of microfluidic devices: Urinary protein uptake by PDMS-based channels after long-term cyclic use.

In the search for transformative technologies for person-centered health monitoring, reusability of microfluidic chips would be a critical design consideration in many biomedical applications. With this unmet need in mind, in this study, we develop and validate a novel microfluidic platform for automated sample pumping with an integrated channel-cleaning procedure. The proposed system leverages micropumps and on-chip solenoid valves to dynamically control fluid flow. We provide a thorough characterization of the custom-designed chip, including quantitative measures of the protein uptake by the chip, as well as cross-contamination using both simulated samples and human urine samples. The effectiveness of the cleaning procedure is assessed by testing the samples collected from the cleaning chip with commercially available urine dipstick protein tests. The results of the longitudinal protein level measurement of the urine samples after the cleaning cycles show high accuracy of protein measurement and negligible protein cross-contamination. Additionally, the cleaning procedure after pumping each sample results in a very low protein uptake (150 ng/cm2). We have also demonstrated that the efficiency of the automated cleaning microfluidic device can be further improved by an anti-fouling coating via PLL-g-PEG pretreatment and a posttreatment via Trypsin. The developed platform could potentially be further miniaturized and integrated into point-of-care devices to provide an effective cleaning process and to enable the reusability of microfluidic devices.

A Bioprinted Liver-on-a-Chip for Drug Screening Applications.

The need for a liver-on-a-chip tissue model for drug screening is particularly important in tissue engineering because of the high frequency of drug-induced liver injury. Recently, a liver tissue model conducive to hepatotoxicity testing was developed by bioprinting hepatic spheroids encapsulated in a hydrogel scaffold into a microfluidic device.

Utilizing stem cells for three-dimensional neural tissue engineering.

Three-dimensional neural tissue engineering has made great strides in developing neural disease models and replacement tissues for patients. However, the need for biomimetic tissue models and effective patient therapies remains unmet. The recent push to expand 2D neural tissue engineering into the third dimension shows great potential to advance the field. Another area which has much to offer to neural tissue engineering is stem cell research. Stem cells are well known for their self-renewal and differentiation potential and have been shown to give rise to tissues with structural and functional properties mimicking natural organs. Application of these capabilities to 3D neural tissue engineering may be highly useful for basic research on neural tissue structure and function, engineering disease models, designing tissues for drug development, and generating replacement tissues with a patient's genetic makeup. Here, we discuss the vast potential, as well as the current challenges, unique to integration of 3D fabrication strategies and stem cells into neural tissue engineering. We also present some of the most significant recent achievements, including nerve guidance conduits to facilitate better healing of nerve injuries, functional 3D biomimetic neural tissue models, physiologically relevant disease models for research purposes, and rapid and effective screening of potential drugs.

3D-printed microfluidic chips with patterned, cell-laden hydrogel constructs.

Three-dimensional (3D) printing offers potential to fabricate high-throughput and low-cost fabrication of microfluidic devices as a promising alternative to traditional techniques which enables efficient design iterations in the development stage. In this study, we demonstrate a single-step fabrication of a 3D transparent microfluidic chip using two alternative techniques: a stereolithography-based desktop 3D printer and a two-step fabrication using an industrial 3D printer based on polyjet technology. This method, compared to conventional fabrication using relatively expensive materials and labor-intensive processes, presents a low-cost, rapid prototyping technique to print functional 3D microfluidic chips. We enhance the capabilities of 3D-printed microfluidic devices by coupling 3D cell encapsulation and spatial patterning within photocrosslinkable gelatin methacryloyl (GelMA). The platform presented here serves as a 3D culture environment for long-term cell culture and growth. Furthermore, we have demonstrated the ability to print complex 3D microfluidic channels to create predictable and controllable fluid flow regimes. Here, we demonstrate the novel use of 3D-printed microfluidic chips as controllable 3D cell culture environments, advancing the applicability of 3D printing to engineering physiological systems for future applications in bioengineering.

Magnetic Levitational Assembly for Living Material Fabrication.

Functional living materials with microscale compositional topographies are prevalent in nature. However, the creation of biomaterials composed of living micro building blocks, each programmed by composition, functionality, and shape, is still a challenge. A powerful yet simple approach to create living materials using a levitation-based magnetic method is presented.

Microscale assembly directed by liquid-based template.

A liquid surface established by standing waves is used as a dynamically reconfigurable template to assemble microscale materials into ordered, symmetric structures in a scalable and parallel manner. The broad applicability of this technology is illustrated by assembling diverse materials from soft matter, rigid bodies, individual cells, cell spheroids and cell-seeded microcarrier beads.

Nanoplasmonic quantitative detection of intact viruses from unprocessed whole blood.

Infectious diseases such as HIV and hepatitis B pose an omnipresent threat to global health. Reliable, fast, accurate, and sensitive platforms that can be deployed at the point-of-care (POC) in multiple settings, such as airports and offices, for detection of infectious pathogens are essential for the management of epidemics and possible biological attacks. To the best of our knowledge, no viral load technology adaptable to the POC settings exists today due to critical technical and biological challenges. Here, we present for the first time a broadly applicable technology for quantitative, nanoplasmonic-based intact virus detection at clinically relevant concentrations. The sensing platform is based on unique nanoplasmonic properties of nanoparticles utilizing immobilized antibodies to selectively capture rapidly evolving viral subtypes. We demonstrate the capture, detection, and quantification of multiple HIV subtypes (A, B, C, D, E, G, and subtype panel) with high repeatability, sensitivity, and specificity down to 98 ± 39 copies/mL (i.e., HIV subtype D) using spiked whole blood samples and clinical discarded HIV-infected patient whole blood samples validated by the gold standard, i.e., RT-qPCR. This platform technology offers an assay time of 1 h and 10 min (1 h for capture, 10 min for detection and data analysis). The presented platform is also able to capture intact viruses at high efficiency using immuno-surface chemistry approaches directly from whole blood samples without any sample preprocessing steps such as spin-down or sorting. Evidence is presented showing the system to be accurate, repeatable, and reliable. Additionally, the presented platform technology can be broadly adapted to detect other pathogens having reasonably well-described biomarkers by adapting the surface chemistry. Thus, this broadly applicable detection platform holds great promise to be implemented at POC settings, hospitals, and primary care settings.

Emerging technologies for assembly of microscale hydrogels.

Assembly of cell encapsulating building blocks (i.e., microscale hydrogels) has significant applications in areas including regenerative medicine, tissue engineering, and cell-based in vitro assays for pharmaceutical research and drug discovery. Inspired by the repeating functional units observed in native tissues and biological systems (e.g., the lobule in liver, the nephron in kidney), assembly technologies aim to generate complex tissue structures by organizing microscale building blocks. Novel assembly technologies enable fabrication of engineered tissue constructs with controlled properties including tunable microarchitectural and predefined compositional features. Recent advances in micro- and nano-scale technologies have enabled engineering of microgel based three dimensional (3D) constructs. There is a need for high-throughput and scalable methods to assemble microscale units with a complex 3D micro-architecture. Emerging assembly methods include novel technologies based on microfluidics, acoustic and magnetic fields, nanotextured surfaces, and surface tension. In this review, we survey emerging microscale hydrogel assembly methods offering rapid, scalable microgel assembly in 3D, and provide future perspectives and discuss potential applications.

Smart interface materials integrated with microfluidics for on-demand local capture and release of cells.

Stimuli responsive, smart interface materials are integrated with microfluidic technologies creating new functions for a broad range of biological and clinical applications by controlling the material and cell interactions. Local capture and on-demand local release of cells are demonstrated with spatial and temporal control in a microfluidic system.