Infertility is a rising global health issue with a far-reaching impact on the socioeconomic livelihoods. As there are highly complex causes of male and female infertility, it is highly desired to promote and maintain reproductive health by the integration of advanced technologies. Biomedical engineering, a mature technology applied in the fields of biology and health care, has emerged as a powerful tool in the diagnosis and treatment of infertility. Nowadays, various promising biomedical engineering approaches are under investigation to address human infertility. Biomedical engineering approaches can not only improve our fundamental understanding of sperm and follicle development in bioengineered devices combined with microfabrication, biomaterials, and relevant cells, but also be applied to repair uterine, ovary, and cervicovaginal tissues and restore tissue function. Here, we introduce the infertility in male and female and provide a comprehensive summary of the various promising biomedical engineering technologies and their applications in reproductive medicine. Also, the challenges and prospects of biomedical engineering technologies for clinical transformation are discussed. We believe that this review will promote communications between engineers, biologists, and clinicians and potentially contribute to the clinical transformation of these innovative research works in the immediate future.

Despite numerous studies on chondrogenesis, the repair of cartilage-particularly the reconstruction of cartilage lacunae through an all-in-one advanced drug delivery system remains limited. In this study, we developed a cartilage lacuna-like hydrogel microsphere system endowed with integrated biological signals, enabling sequential immunomodulation and endogenous articular cartilage regeneration. We first integrated the chondrogenic growth factor transforming growth factor-β3 (TGF-β3) into mesoporous silica nanoparticles (MSNs). Then, TGF-β3@MSNs and insulin-like growth factor 1 (IGF-1) were encapsulated within microspheres made of polydopamine (pDA). In the final step, growth factor-loaded MSN@pDA and a chitosan (CS) hydrogel containing platelet-derived growth factor-BB (PDGF-BB) were blended to produce growth factors loaded composite microspheres (GFs@μS) using microfluidic technology. The presence of pDA reduced the initial acute inflammatory response, and the early, robust release of PDGF-BB aided in attracting endogenous stem cells. Over the subsequent weeks, the continuous release of IGF-1 and TGF-β3 amplified chondrogenesis and matrix formation. μS were incorporated into an acellular cartilage extracellular matrix (ACECM) and combined with a polydopamine-modified polycaprolactone (PCL) structure to produce a tissue-engineered scaffold that mimicked the structure of the cartilage lacunae evenly distributed in the cartilage matrix, resulting in enhanced cartilage repair and patellar cartilage protection. This research provides a strategic pathway for optimizing growth factor delivery and ensuring prolonged microenvironmental remodeling, leading to efficient articular cartilage regeneration.

Cell co-culture technology aims to study the communication mechanism between cells and to better reveal the interactions and regulatory mechanisms involved in processes such as cell growth, differentiation, apoptosis, and other cellular activities. This is achieved by simulating the complex organismic environment. Such studies are of great significance for understanding the physiological and pathological processes of multicellular organisms. As an emerging cell cultivation technology, 3D cell co-culture technology, based on microfluidic chips, can efficiently, rapidly, and accurately achieve cell co-culture. This is accomplished by leveraging the unique microchannel structures and flow characteristics of microfluidic chips. The technology can simulate the native microenvironment of cell growth, providing a new technical platform for studying intercellular communication. It has been widely used in the research of oncology, immunology, neuroscience, and other fields. In this review, we summarize and provide insights into the design of cell co-culture systems on microfluidic chips, the detection methods employed in co-culture systems, and the applications of these models.

UNASSIGNED: Sexually transmitted infections (STIs) are among the most common infectious diseases worldwide, often leading to coinfections. Timely detection of genital tract pathogens in at-risk populations is crucial for preventing STIs. We evaluated the NAP-Fluo Cycler System, an innovative microfluidic nucleic acid detection platform, for its ability to simultaneously identify Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Ureaplasma urealyticum (UU), Mycoplasma genitalium (MG), and Mycoplasma hominis (MH) in urethral or cervical secretions.
UNASSIGNED: The limits of detection (LODs), repeatability, specificity, and interference resistance of the system were evaluated using standard strains, a panel of 24 pathogens, and seven interferents. We used the system to analyze 302 clinical samples and compared the results with those of five approved commercial reference kits.
UNASSIGNED: The system achieved LODs of 500 IFU/mL, 500 CFU/mL, and 500 CCU/mL for CT, NG, and UU/MG/MH, respectively, demonstrating high stability (coefficient of variation <1.1 %), specificity, and resistance to interference. Among 302 clinical samples, 237 tested positive with single, dual, and triple infection rates of 35.6 %, 16.2 %, and 3.0 %, respectively. The reference kits detected 138 positive samples. The concordance rates with commercial reference kits were 100 % for UU, NG, and MH; 94.85 % for CT; and 80.00 % for MG.
UNASSIGNED: This system offers a streamlined, rapid, and multiplex detection method that reduces testing time and complexity. Although it performs well with pure strains, it has limitations when using clinical samples of CT and MG, suggesting the need for further refinement before its widespread use in the clinic.

Optically induced dielectrophoresis (ODEP)-based microparticle sorting and separation is regarded as promising. However, current methods normally lack the downstream process for the transportation and collection of separated microparticles, which could limit its applications. To address this issue, an ODEP microfluidic chip encompassing three microchannels that join only at the central part of the microchannels (i.e., the working zone) was designed. During operation, three laminar flows were generated in the zone, where two dynamic light bar arrays were designed to sort and separate PS (polystyrene) microbeads of different sizes in a continuous manner. The separated PS microbeads were then continuously transported in laminar flows in a partition manner for the final collection. The results revealed that the method was capable of sorting and separating PS microbeads in a high-purity manner (e.g., the microbead purity values were 89.9 ± 3.7, 88.0 ± 2.5, and 92.8 ± 6.5% for the 5.8, 10.8, and 15.8 μm microbeads harvested, respectively). Overall, this study demonstrated the use of laminar flow and ODEP to achieve size-based sorting, separation, and collection of microparticles in a continuous and high-performance manner. Apart from the demonstration, this method can also be utilized for size-based sorting and the separation of other biological or nonbiological microparticles.

Microfluidic technology, as a continuous and mass preparation method of nanoparticles, has attracted much attention in recent years. In this study, zein nanoparticles (ZNPs) were continuously fabricated in a highly controlled manner by combining a microfluidics platform with the antisolvent method. The impact of ethanol content (60~95%, v/v) and flow rates of inner and outer phases in the microfluidics platform on particle properties were examined. Among all ZNPS, 90%-ZNPs have the highest solubility (32.83%) and the lowest hydrophobicity (90.43), which is the reverse point of the hydrophobicity of ZNPs. Moreover, when the inner phase flow rate was 1.5 mL/h, the particle size decreased significantly from 182.81 nm to 133.13 nm as the outer phase flow rate increased from 10 mL/h to 50 mL/h. The results revealed that ethanol content had significant impacts on hydrophilic-hydrophobic properties of ZNPs. The flow rates of ethanol-water solutions and deionized water (solvent and antisolvent) in the microfluidics platform significantly affected the particle size of ZNPs. These findings demonstrated that the combined application of a microfluidics platform and an antisolvent method could be an effective pathway for precisely controlling the fabrication process of protein nanoparticles and modulating their physicochemical properties.

This study\'s main objective was to fabricate an innovative three-dimensional microfluidic platform suitable for well-controlled chemical syntheses required for producing fine-tuned nanostructured materials. This work proposes using vortex mixing principles confined within a 3D multilayered microreactor to synthesize magnetic core-shell nanoparticles with tailored dimensions and polydispersity. The newly designed microfluidic platform allowed the simultaneous obtainment of Fe3O4 cores and their functionalization with a salicylic acid shell in a short reaction time and under a high flow rate. Synthesis optimization was also performed, employing the variation in the reagents ratio to highlight the concentration domains in which magnetite is mainly produced, the formation of nanoparticles with different diameters and low polydispersity, and the stability of colloidal dispersions in water. The obtained materials were further characterized by X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM), with the experimental results confirming the production of salicylic acid-functionalized iron oxide (Fe3O4-SA) nanoparticles adapted for different further applications.

UNASSIGNED: The commercial docetaxel (DTX) formulation causes severe side effects due to polysorbate 80 and ethanol. Novel surfactant-free nanoparticle (NP) systems are needed to improve bioavailability and reduce side effects. However, controlling the particle size and stability of NPs and improving the batch-to-batch variation are the major challenges.
UNASSIGNED: DTX-loaded bovine serum albumin nanoparticles (DTX-BSA-NPs) were prepared by a novel thermal-driven self-assembly/microfluidic technology. Single-factor analysis and orthogonal test were conducted to obtain the optimal formulation of DTX-BSA-NPs in terms of particle size, encapsulation efficiency (EE), and drug loading (DL). The effects of oil/water flow rate and pump pressure on the particle size, EE, and DL were investigated to optimize the preparation process of DTX-BSA-NPs. The drug release, physicochemical properties, stability, and pharmacokinetics of NPs were evaluated.
UNASSIGNED: The optimized DTX-BSA-NPs were uniform, with a particle size of 118.30 nm, EE of 89.04%, and DL of 8.27%. They showed a sustained release of 70% over 96 hours and an increased stability. There were some interactions between the drug and excipients in DTX-BSA-NPs. The half-life, mean residence time, and area under the curve (AUC) of DTX-BSA-NPs increased, but plasma clearance decreased when compared with DTX.
UNASSIGNED: The thermal-driven self-assembly/microfluidic combination method effectively produces BSA-based NPs that improve the bioavailability and stability of DTX, offering a promising alternative to traditional formulations.

This review outlines the evolutionary journey from traditional two-dimensional (2D) cell culture to the revolutionary field of organ-on-a-chip technology. Organ-on-a-chip technology integrates microfluidic systems to mimic the complex physiological environments of human organs, surpassing the limitations of conventional 2D cultures. This evolution has opened new possibilities for understanding cell-cell interactions, cellular responses, drug screening, and disease modeling. However, the design and manufacture of microchips significantly influence their functionality, reliability, and applicability to different biomedical applications. Therefore, it is important to carefully consider design parameters, including the number of channels (single, double, or multi-channels), the channel shape, and the biological context. Simultaneously, the selection of appropriate materials compatible with the cells and fabrication methods optimize the chips\' capabilities for specific applications, mitigating some disadvantages associated with these systems. Furthermore, the success of organ-on-a-chip platforms greatly depends on the careful selection and utilization of cell resources. Advances in stem cell technology and tissue engineering have contributed to the availability of diverse cell sources, facilitating the development of more accurate and reliable organ-on-a-chip models. In conclusion, a holistic perspective of in vitro cellular modeling is provided, highlighting the integration of microfluidic technology and meticulous chip design, which play a pivotal role in replicating organ-specific microenvironments. At the same time, the sensible use of cell resources ensures the fidelity and applicability of these innovative platforms in several biomedical applications.

Simple, sensitive, and accurate molecular diagnostics are critical for preventing rapid spread of infection and initiating early treatment of diseases. However, current molecular detection methods typically rely on extensive nucleic acid sample preparation and expensive instrumentation. Here, a simple, fully integrated, lab-in-a-magnetofluidic tube (LIAMT) platform is presented for \"sample-to-result\" molecular detection of virus. By leveraging magnetofluidic transport of micro/nano magnetic beads, the LIAMT device integrates viral lysis, nucleic acid extraction, isothermal amplification, and CRISPR detection within a single engineered microcentrifuge tube. To enable point-of-care molecular diagnostics, a palm-sized processor is developed for magnetofluidic separation, nucleic acid amplification, and visual fluorescence detection. The LIAMT platform is applied to detect SARS-CoV-2 and HIV viruses, achieving a detection sensitivity of 73.4 and 63.9 copies µL-1, respectively. Its clinical utility is further demonstrated by detecting SARS-CoV-2 and HIV in clinical samples. This simple, affordable, and portable LIAMT platform holds promise for rapid and sensitive molecular diagnostics of infectious diseases at the point-of-care.