Recent Strategies and Future Recommendations for the Fabrication of Antimicrobial, Antibiofilm, and Antibiofouling Biomaterials.

Biomaterials and biomedical devices induced life-threatening bacterial infections and other biological adverse effects such as thrombosis and fibrosis have posed a significant threat to global healthcare. Bacterial infections and adverse biological effects are often caused by the formation of microbial biofilms and the adherence of various biomacromolecules, such as platelets, proteins, fibroblasts, and immune cells, to the surfaces of biomaterials and biomedical devices. Due to the programmed interconnected networking of bacteria in microbial biofilms, they are challenging to treat and can withstand several doses of antibiotics. Additionally, antibiotics can kill bacteria but do not prevent the adsorption of biomacromolecules from physiological fluids or implanting sites, which generates a conditioning layer that promotes bacteria's reattachment, development, and eventual biofilm formation. In these viewpoints, we highlighted the magnitude of biomaterials and biomedical device-induced infections, the role of biofilm formation, and biomacromolecule adhesion in human pathogenesis. We then discussed the solutions practiced in healthcare systems for curing biomaterials and biomedical device-induced infections and their limitations. Moreover, this review comprehensively elaborated on the recent advances in designing and fabricating biomaterials and biomedical devices with these three properties: antibacterial (bacterial killing), antibiofilm (biofilm inhibition/prevention), and antibiofouling (biofouling inhibition/prevention) against microbial species and against the adhesion of other biomacromolecules. Besides we also recommended potential directions for further investigations.

Combined Synthesis of Cerium Oxide Particles for Effective Anti-Bacterial and Anti-Cancer Nanotherapeutics.

Introduction: Kochiae Fructus has been widely used in Chinese Herbal medicine to treat various diseases. We report a rapid and eco-friendly approach for cerium oxide (CeO2) nanoparticles (NPs) synthesis using the extract of medicinally important plant "Kochiae Fructus", and the synthesized NPs were named KF-CeO2 NPs. Methods: Various spectroscopic approaches such as transmission electron microscope (TEM), powder X-ray diffraction (XRD), and energy-dispersive X-Ray (EDX) were used to characterize the KF-CeO2 NPs effectively. The antibacterial and biofilm inhibition activity of KF-CeO2 NPs against Gram-positive and Gram-negative multi-drug resistant (MDR) bacteria was determined using the serial dilution method and XTT assay. KF-CeO2 NPs were assessed for anticancer activity against HeLa cancer cells using an MTT assay. Cytobiocompatibility was determined in two normal cell lines (3T3 and hMSC). Results and Discussion: The average size of the KF-CeO2 NPs was 11.3 ± 3.9 nm with spherical morphology. KF-CeO2 NPs demonstrated a greater than 95% bactericidal efficacy against MDR microorganisms. In addition, KF-CeO2 NPs strongly suppressed (more than 79%) the biofilms of MDR bacteria, indicating their potential for addressing antibiotic resistance issues. Compared to Kochiae Fructus extract and CH-CeO2 NPs, they exhibited significant cytotoxic effects (35.60% cell viability) on HeLa cancer cells. In addition, the KF-CeO2 NPs were shown to be highly biocompatible with hMSC and 3T3 cell lines (85.13% and 81.17% cell viability, respectively), suggesting that they may be employed in biological systems. Conclusion: These data indicate that KF-CeO2 NPs synthesized using Kochiae Fructus extract are promising alternative treatments for MDR. In addition, this study will give the potential for the sustained development of biocompatible NPs with enhanced biological capabilities derived from vital pharmaceutical plants.

UV-irradiating synthesis of cyclodextrin-silver nanocluster decorated TiO2 nanoparticles for photocatalytic enhanced anticancer effect on HeLa cancer cells.

Titanium dioxide (TiO2) has emerged as a viable choice for several biological and environmental applications because of its high efficiency, cheap cost, and high photostability. In pursuit of this purpose, the research of its many forms has been influenced by these unique aspects. The development of novel TiO2-based hybrid materials with enhanced photocatalytically induced anticancer activity has gained tremendous attention. Here, we have developed a novel photocatalytic material (TiO2-Ag NPs@-CD) by decorating ultrasmall silver nanoparticles (Ag NPs) with per-6-thio-ß-cyclodextrin (SH-ß-CD) on TiO2 NPs. TiO2-Ag NPs@-CD were characterized by employing various characterization techniques and evaluated for their anticancer activity against HeLa cancer cells using an MTT assay. The biocompatibility of the designed nanoparticles was determined on two normal cell lines, namely, 3T3 and human mesenchymal stem cells (hMSCs). The results show that the TiO2-Ag NPs@-CD induced superior cytotoxic effects on HeLa cancer cells at a concentration of 64 µg/ml. Live-dead staining and oxidative stress investigations demonstrated that cell membrane disintegration and ROS-induced oxidative stress generated by TiO2-Ag NPs@-CD inside HeLa cancer cells are the contributing factors to their exceptional anti-cancer performance. Moreover, TiO2-Ag NPs@-CD exhibited good biocompatibility with 3T3 and hMSCs. These results indicated that the combination of all three components-a silver core, SH-ß-CD ligands, and TiO2 nanoparticles-produced a synergistic anticancer effect. Hence, the TiO2-Ag NPs@-CD is a promising material that can be employed for different biological applications.

High-efficiency quantitative control of mitochondrial transfer based on droplet microfluidics and its application on muscle regeneration.

Mitochondrial transfer is a spontaneous process to restore damaged cells in various pathological conditions. The transfer of mitochondria to cell therapy products before their administration can enhance therapeutic outcomes. However, the low efficiency of previously reported methods limits their clinical application. Here, we developed a droplet microfluidics-based mitochondrial transfer technique that can achieve high-efficiency and high-throughput quantitative mitochondrial transfer to single cells. Because mitochondria are essential for muscles, myoblast cells and a muscle injury model were used as a proof-of-concept model to evaluate the proposed technique. In vitro and in vivo experiments demonstrated that C2C12 cells with 31 transferred mitochondria had significant improvements in cellular functions compared to those with 0, 8, and 14 transferred mitochondria and also had better therapeutic effects on muscle regeneration. The proposed technique can considerably promote the clinical application of mitochondrial transfer, with optimized cell function improvements, for the cell therapy of mitochondria-related diseases.

Advanced tools and methods for single-cell surgery.

Highly precise micromanipulation tools that can manipulate and interrogate cell organelles and components must be developed to support the rapid development of new cell-based medical therapies, thereby facilitating in-depth understanding of cell dynamics, cell component functions, and disease mechanisms. This paper presents a literature review on micro/nanomanipulation tools and their control methods for single-cell surgery. Micromanipulation methods specifically based on laser, microneedle, and untethered micro/nanotools are presented in detail. The limitations of these techniques are also discussed. The biological significance and clinical applications of single-cell surgery are also addressed in this paper.

Automated Optical Tweezers Manipulation to Transfer Mitochondria from Fetal to Adult MSCs to Improve Antiaging Gene Expressions.

Mitochondrial dysfunction is considered to be an important factor that leads to aging and premature aging diseases. Transferring mitochondria to cells is an emerging and promising technique for the therapy of mitochondrial deoxyribonucleic acid (mtDNA)-related diseases. This paper presents a unique method of controlling the quality and quantity of mitochondria transferred to single cells using an automated optical tweezer-based micromanipulation system. The proposed method can automatically, accurately, and efficiently collect and transport healthy mitochondria to cells, and the recipient cells then take up the mitochondria through endocytosis. The results of the study reveal the possibility of using mitochondria from fetal mesenchymal stem cells (fMSCs) as a potential source to reverse the aging-related phenotype and improve metabolic activities in adult mesenchymal stem cells (aMSCs). The results of the quantitative polymerase chain reaction analysis show that the transfer of isolated mitochondria from fMSCs to a single aMSC can significantly increase the antiaging and metabolic gene expression in the aMSC. The proposed mitochondrial transfer method can greatly promote precision medicine for cell therapy of mtDNA-related diseases.

Gravitational sedimentation-based approach for ultra-simple and flexible cell patterning coculture on microfluidic device.

Combining patterning coculture technique with microfluidics enables the reconstruction of complex in-vivo system to facilitate in-vitro studies on cell-cell and cell-environment interactions. However, simple and versatile approaches for patterning coculture of cells on microfluidic platforms remain lacking. In this study, a novel gravitational sedimentation-based approach is presented to achieve ultra-simple and flexible cell patterning coculture on a microfluidic platform, where multiple cell types can be patterned simultaneously to form a well-organized cell coculture. In contrast to other approaches, the proposed approach allows the rapid patterning of multiple cell types in microfluidic channels without the use of sheath flow and a prepatterned functional surface. This feature greatly simplifies the experimental setup, operation, and chip fabrication. Moreover, cell patterning can be adjusted by simply modifying the cell-loading tubing direction, thereby enabling great flexibility for the construction of different cell patterns without complicating the chip design and flow control. A series of physical and biological experiments are conducted to validate the proposed approach. This research paves a new way for building physiologically realistic in-vitro coculture models on microfluidic platforms for various applications, such as cell-cell interaction and drug screening.

Out-of-Plane Rotation Control of Biological Cells With a Robot-Tweezers Manipulation System for Orientation-Based Cell Surgery.

In many cell surgery applications, cell must be oriented properly such that the microsurgery tool can access the target components with minimum damage to the cell. In this paper, a scheme for out of image plane orientation control of suspended biological cells using robotic controlled optical tweezers is presented for orientation-based cell surgery. Based on our previous work on planar cell rotation using optical tweezers, the dynamic model of cell out-of-plane orientation control is formulated by using the T-matrix approach. Vision-based algorithms are developed to extract the cell out of image plane orientation angles, based on 2-D image slices obtained under an optical microscope. A robust feedback controller is then proposed to achieve cell out-of-plane rotation. Experiments of automated out of image plane rotational control for cell nucleus extraction surgery are performed to demonstrate the effectiveness of the proposed approach. This approach advances robot-aided single cell manipulation and produces impactful benefits to cell surgery applications such as nucleus transplantation and organelle biopsy in precision medicine.

Achieving Automated Organelle Biopsy on Small Single Cells Using a Cell Surgery Robotic System.

Single cell surgery such as manipulation or removal of subcellular components or/and organelles from single cells is increasingly used for the study of diseases and their causes in precision medicine. This paper presents a robotic surgery system to achieve automated organelle biopsy of single cells with dimensions of less than 20 µm in diameter. The complexity of spatial detection of the organelle position is reduced by patterning the cells using a microfluidic chip device. A sliding mode nonlinear controller is developed to enable extraction of organelles, such as the mitochondria and the nucleus, from single cells with high precision. An image processing algorithm is also developed to automatically detect the position of the desired organelle. The effectiveness of the proposed robotic surgery system is demonstrated experimentally with automated extraction of mitochondria and nucleus from human acute promyelocytic leukemia cells and human fibroblast cells. Extraction is followed by biological tests to indicate the functionality of biopsied mitochondria as well as the cell viability after removal of mitochondria. The results presented here have revealed that the proposed approach of automated organelle biopsy on single small cells is feasible.

Manipulation of Biological Cells Using a Robot-Aided Optical Tweezers System.

This article reviews the autonomous manipulation strategies of biological cells utilizing optical tweezers, mainly including optical direct and indirect manipulation strategies. The typical and latest achievements in the optical manipulation of cells are presented, and the existing challenges for autonomous optical manipulation of biological cells are also introduced. Moreover, the integrations of optical tweezers with other manipulation tools are presented, which broadens the applications of optical tweezers in the biomedical manipulation areas and will also foster new developments in cell-based physiology and pathology studies, such as cell migration, single cell surgery, and preimplantation genetic diagnosis (PGD).

A kernel-based multivariate feature selection method for microarray data classification.

High dimensionality and small sample sizes, and their inherent risk of overfitting, pose great challenges for constructing efficient classifiers in microarray data classification. Therefore a feature selection technique should be conducted prior to data classification to enhance prediction performance. In general, filter methods can be considered as principal or auxiliary selection mechanism because of their simplicity, scalability, and low computational complexity. However, a series of trivial examples show that filter methods result in less accurate performance because they ignore the dependencies of features. Although few publications have devoted their attention to reveal the relationship of features by multivariate-based methods, these methods describe relationships among features only by linear methods. While simple linear combination relationship restrict the improvement in performance. In this paper, we used kernel method to discover inherent nonlinear correlations among features as well as between feature and target. Moreover, the number of orthogonal components was determined by kernel Fishers linear discriminant analysis (FLDA) in a self-adaptive manner rather than by manual parameter settings. In order to reveal the effectiveness of our method we performed several experiments and compared the results between our method and other competitive multivariate-based features selectors. In our comparison, we used two classifiers (support vector machine, [Formula: see text]-nearest neighbor) on two group datasets, namely two-class and multi-class datasets. Experimental results demonstrate that the performance of our method is better than others, especially on three hard-classify datasets, namely Wang's Breast Cancer, Gordon's Lung Adenocarcinoma and Pomeroy's Medulloblastoma.