A multicrosslinked network composite hydrogel scaffold based on DLP photocuring printing for nasal cartilage repair.

Natural hydrogels are widely employed in tissue engineering and have excellent biodegradability and biocompatibility. Unfortunately, the utilization of such hydrogels in the field of three-dimensional (3D) printing nasal cartilage is constrained by their subpar mechanical characteristics. In this study, we provide a multicrosslinked network hybrid ink made of photocurable gelatin, hyaluronic acid, and acrylamide (AM). The ink may be processed into intricate 3D hydrogel structures with good biocompatibility and high stiffness properties using 3D printing technology based on digital light processing (DLP), including intricate shapes resembling noses. By varying the AM content, the mechanical behavior and biocompatibility of the hydrogels can be adjusted. In comparison to the gelatin methacryloyl (GelMA)/hyaluronic acid methacryloyl (HAMA) hydrogel, adding AM considerably enhances the hydrogel's mechanical properties while also enhancing printing quality. Meanwhile, the biocompatibility of the multicrosslinked network hydrogels and the development of cartilage were assessed using neonatal Sprague-Dawley (SD) rat chondrocytes (CChons). Cells sown on the hydrogels considerably multiplied after 7 days of culture and kept up the expression of particular proteins. Together, our findings point to GelMA/HAMA/polyacrylamide (PAM) hydrogel as a potential material for nasal cartilage restoration. The photocuring multicrosslinked network ink composed of appropriate proportions of GelMA/HAMA/PAM is very suitable for DLP 3D printing and will play an important role in the construction of nasal cartilage, ear cartilage, articular cartilage, and other tissues and organs in the future. Notably, previous studies have not explored the application of 3D-printed GelMA/HAMA/PAM hydrogels for nasal cartilage regeneration.

Effective Combination of Targeted Therapies with Sonodynamic Treatment for Use in Exploring Differences in Therapeutic Efficacy across Organelle Targets.

Acoustic kinetic therapy systems that target specific organelles can improve the precision of a sonosensitizer, which is a perfect combination of targeted therapy and sonodynamic therapy (SDT) and plays an important role in current acoustic kinetic therapy. In this study, we loaded PpIX, a sonosensitizer, on targeted-functional carbon dots (CDs) via an amide reaction and then generated the mitochondria-targeted system (Mit-CDs-PpIX) and nucleus-targeted system (Nuc-CDs-PpIX), respectively, to deliver the sonosensitizer. Both systems exhibited minimal cytotoxicity in the absence of ultrasound stimulation. The efficacy of the targeted SDT systems was investigated using methylthiazol tetrazolium (MTT) assays, live/dead staining, flow cytometry, etc. Compared with the free PpIX and mitochondria-targeted system, the nucleus-targeted system is more potent in killing effect under ultrasound stimulation and induces apoptosis with higher intensity. To achieve the equal killing effect, the effective concentration of Nuc-CDs-PpIX is just one third of that of Mit-CDs-PpIX.

3D Bioprinting-Based Dopamine-Coupled Flexible Material for Nasal Cartilage Repair.

INTRODUCTION: Since 3D printing can be used to design implants according to the specific conditions of patients, it has become an emerging technology in tissue engineering and regenerative medicine. How to improve the mechanical, elastic and adhesion properties of 3D-printed photocrosslinked hydrogels is the focus of cartilage tissue repair and reconstruction research. MATERIALS AND METHODS: We established a strategy for toughening hydrogels by mixing GelMA-DOPA (GD), which is prepared by coupling dopamine (DA) with GelMA, with HAMA, bacterial cellulose (BC) to produce composite hydrogels (HB-GD). HB-GD hydrogel scaffolds were characterized in vitro by scanning electron microscopy (SEM), Young's modulus, swelling property and rheological property tests. And biocompatibility and chondrogenic ability were tested by live/dead staining, DNA quantitative analysis and immunofluorescence staining. Combined with 3D bioprinting technology, mouse chondrocytes (ADTC5) were added to form a biological chain to construct an in vitro model, and the feasibility of the model for nasal cartilage regeneration was verified by cytology evaluation. RESULTS: With the increase of GD concentration, the toughness of the composite hydrogel increased (47.0 ± 2.7 kPa (HB-5GD)-158 ± 3.2 kPa (HB-20GD)), and it had excellent swelling properties, rheological properties and printing properties. The HB-GD composite hydrogel promoted the proliferation and differentiation of ATDC5. Cells in 3D printed scaffolds had higher survival rates (> 95%) and better protein expression than the encapsulated cultures. CONCLUSION: The HB-10GD hydrogel can be made into a porous scaffold with precise shape, good internal pore structure, high mechanical strength and good swelling rate through extrusion 3D printing. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

A mechanical HSA biosensor based on multi-field-coupling-mediated magnetic sensitization strategy.

The conventional mechanical biosensor based on stress and electrical conversion can be an effective method to detect key human biomarkers for clinical diagnosis and early disease prevention. However, the applications of this type of biosensor are greatly limited due to their unsatisfactory sensitivity. In this work, a magnetic-sensitized (MS) mechanical biosensor based on multi-field coupling was developed for higher sensitivity, giving access to detect human serum albumin (HSA). Via introducing secondary magnetic antibodies labeled with magnetized Fe2O3 nanoparticles to the stress and electrical conversion element of the MS-biosensor, the multi-field coupling was realized based on stress, electricity, and magnetism. Under the action of the magnetic field, the magnetic force of the secondary magnetic antibody and the stress of antigen-antibody binding jointly drove and enhanced the deformation of the MS-biosensor, amplifying the electrical signal, and realizing magnetic sensitization. The HSA was detected by the MS-biosensor at a range of 0-80 µg/mL with a limit of detection (LOD) of 0.14 µg/mL, demonstrating the high performance of the MS-biosensor. Moreover, the MS-biosensor showed high selectivity, specificity, and stability, indicating that the magnetic sensitization strategy of the MS-biosensor was significant for the clinical application of mechanical biosensors.

3D printing to construct in vitro multicellular models of melanoma.

Currently, there is a lack of suitable models for in-vitro studies of malignant melanoma and traditional single cell culture models no longer reproduce tumor structure and physiological complexity well. The tumor microenvironment is closely related to carcinogenesis and it is particularly important to understand how tumor cells interact and communicate with surrounding nonmalignant cells. Three-dimensional (3D) in vitro multicellular culture models can better simulate the tumor microenvironment due to their excellent physicochemical properties. In this study, 3D composite hydrogel scaffolds were prepared from gelatin methacrylate and polyethylene glycol diacrylate hydrogels by 3D printing and light curing techniques, and 3D multicellular in vitro tumor culture models were established by inoculating human melanoma cells (A375) and human fibroblasts cells on them. The cell proliferation, migration, invasion, and drug resistance of the 3D multicellular in vitro model was evaluated. Compared with the single-cell model, the cells in the multicellular model had higher proliferation activity and migration ability, and were easy to form dense structures. Several tumor cell markers, such as matrix metalloproteinase-9 (MMP-9), MMP-2, and vascular endothelial growth factor, were highly expressed in the multicellular culture model, which were more favorable for tumor development. In addition, higher cell survival rate was observed after exposure to luteolin. The anticancer drug resistance result of the malignant melanoma cells in the 3D bioprinted construct demonstrated physiological properties, suggesting the promising potential of current 3D printed tumor model in the development of personalized therapy, especially for discovery of more conducive targeted drugs.

Collagen-coated agarose-chitosan scaffold used as a skin substitute.

A single biomaterial is disadvantageous for constructing skin in vitro, so a mixed biomaterial is more conducive to skin research. In this study, agarose-chitosan scaffolds with a final concentration of 4% were constructed by freeze-drying, in which the concentration ratios of agarose to chitosan were 1:3, 2:2, and 3:1. The scaffolds were coated with a 3 mg/ml collagen solution, and the mechanical properties were evaluated by studying density, porosity, swelling rate, and degradation rate. The results demonstrated that the agarose-chitosan scaffolds were porous, with porosity reaching 93%. Their densities ranged from 0.1 to 0.16 g/cm3 . Analysis of Young's modulus showed that the mechanical properties of the agarose-chitosan scaffolds were significantly enhanced when the agarose content in the agarose-chitosan scaffolds was increased. Moreover, the density and Young's modulus of the agarose-chitosan scaffolds of different concentration ratios were significantly different (p < 0.01). These scaffolds can withstand a certain amount of external pressure, such as that of human skin, making them more suitable for further skin replacement research. In addition, the results of thiazolyl blue tetrazolium bromide (MTT) cell assay and immunofluorescence staining showed that the collagen-coated agarose-chitosan scaffolds were conducive to keratinocyte proliferation and differentiation. The MTT results revealed significant differences between the agarose-chitosan scaffolds coated with collagen and the agarose-chitosan scaffolds without collagen (p < 0.05). This study provides the potential for in vitro skin research and applications.

Path Planning for Obstacle Avoidance of Robot Arm Based on Improved Potential Field Method.

In medical and surgical scenarios, the trajectory planning of a collaborative robot arm is a difficult problem. The artificial potential field (APF) algorithm is a classic method for robot trajectory planning, which has the characteristics of good real-time performance and low computing consumption. There are many variants of the APF algorithm, among which the most widely used variants is the velocity potential field (VPF) algorithm. However, the traditional VPF algorithm has inherent defects and problems, such as easily falling into local minimum, being unable to reach the target, poor dynamic obstacle avoidance ability, and safety and efficiency problems. Therefore, this work presents the improved velocity potential field (IVPF) algorithm, which considers direction factors, obstacle velocity factor, and tangential velocity. When encountering dynamic obstacles, the IVPF algorithm can avoid obstacles better to ensure the safety of both the human and robot arm. The IVPF algorithm also does not easily fall into a local problem when encountering different obstacles. The experiments informed the RRT* algorithm, VPF algorithm, and IVPF algorithm for comparison. Compared with the informed RRT* and VPF algorithm, the result of experiments indicate that the performances of the IVPF algorithm have significant improvements when dealing with different obstacles. The main aim of this paper is to provide a safe and efficient path planning algorithm for the robot arm in the medical field. The proposed algorithm can ensure the safety of both the human and the robot arm when the medical and surgical robot arm is working, and enables the robot arm to cope with emergencies and perform tasks better. The application of the proposed algorithm could make the collaborative robots work in a flexible and safe condition, which could open up new opportunities for the future development of medical and surgical scenarios.

Photo-crosslinked hydrogels for tissue engineering of corneal epithelium.

The vast majority of patients with corneal blindness cannot recover their vision due to the serious shortage of donor cornea. However, the technology to construct a feasible corneal substitute is a promising treatment method for corneal blindness. In this paper, methacrylated gelatin (GelMA)-methacrylated hyaluronic acid (HAMA) double network (GHDN) hydrogels were prepared by modifying gelatin and hyaluronic acid with methacrylate anhydride (MA). GHDN hydrogel was compared with GelMA single network and HAMA single network hydrogels through characterization experiments of mechanical properties, optical properties, hydrophilicity and in-situ degradation in vitro. At the same time, the biocompatibility of hydrogel was tested by inoculating rabbit corneal epithelial cells (CEpCs) epidermal cells on hydrogels using CCK-8 test, live/dead staining, immunofluorescence staining and qRT-PCR. It was found that the GHDN hydrogel has optical transparency in the visible region, and its mechanical properties are better than those of GelMA and HAMA hydrogels, and its hydrophilicity is similar to that of normal human corneas. The results of in vitro hydrogel culture of CEpCs showed that the proliferation of CEpCs on GHDN hydrogel was two times higher than that of HAMA hydrogel, and the expression of specific marker Cytokeratin 3 (CK3) and Cytokeratin 12 (CK12) could be better maintained on GHDN hydrogel. All the experimental results proved that GHDN hydrogel has good physical properties and biocompatibility and is a potential candidate for corneal tissue engineering scaffolds.

Progress of 3D Printing Techniques for Nasal Cartilage Regeneration.

Once cartilage is damaged, its self-repair capacity is very limited. The strategy of tissue engineering has brought a new idea for repairing cartilage defect and cartilage regeneration. In particular, nasal cartilage regeneration is a challenge because of the steady increase in nasal reconstruction after oncologic resection, trauma, or rhinoplasty. From this perspective, three-dimensional (3D) printing has emerged as a promising technology to address the complexity of nasal cartilage regeneration, using patient's image data and computer-aided deposition of cells and biomaterials to precisely fabricate complex, personalized tissue-engineered constructs. In this review, we summarized the major progress of three prevalent 3D printing approaches, including inkjet-based printing, extrusion-based printing and laser-assisted printing. Examples are highlighted to illustrate 3D printing for nasal cartilage regeneration, with special focus on the selection of seeded cell, scaffolds and growth factors. The purpose of this paper is to systematically review recent research about the challenges and progress and look forward to the future of 3D printing techniques for nasal cartilage regeneration.Level of Evidence III This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266 .

Enhanced solar water splitting using plasmon-induced resonance energy transfer and unidirectional charge carrier transport.

Solar water splitting by photoelectrochemical (PEC) reactions is promising for hydrogen production. The gold nanoparticles (AuNPs) are often applied to promote the visible response of wideband photocatalysts. However, in a typical TiO2/AuNPs structure, the opposite transfer direction of excited electrons between AuNPs and TiO2 under visible light and UV light severely limits the solar PEC performance. Here we present a unique Pt/TiO2/Cu2O/NiO/AuNPs photocathode, in which the NiO hole transport layer (HTL) is inserted between AuNPs and Cu2O to achieve unidirectional transport of charge carriers and prominent plasmon-induced resonance energy transfer (PIRET) between AuNPs and Cu2O. The measured applied bias photon-to-current efficiency and the hydrogen production rate under AM 1.5G illumination can reach 1.5% and 16.4 µmol·cm-2·h-1, respectively. This work is original in using the NiO film as the PIRET spacer and provides a promising photoelectrode for energy-efficient solar water splitting.

A low-cost and high-efficiency method for four-inch silicon nano-mold by proximity UV exposure.

Nano-mold is an essential tool for nano-imprinting. However, large-area nano-mold fabrication relies on expensive equipment or complicated processing. Silicon nano-molds were achieved by proximity ultraviolet lithography and reactive ion etching (RIE). By optimizing the parameters in the processes of exposure, development, and RIE, silicon nano-mold with nano-scale ridges were fabricated with high-precision. The achieved minimum width of nano-ridges was 263 nm. This method is capable of fabricating silicon nano-mold covering four-inch wafer, which is simple, efficient and free from costly equipment.

A novel paper biosensor based on Fe3O4@SiO2-NH2and MWCNTs for rapid detection of pseudorabies virus.

In this study, a novel paper biosensor based on Fe3O4@SiO2-NH2magnetic polymer microspheres and multi walled carbon nanotubes (MWCNTs) for rapid detection of pseudorabies virus (PRV) was first developed. Fe3O4@SiO2-NH2were functionalized with PRV antibody and doped in cellulose nitrate paper to fabricate the magnetic paper biosensor with good magnetic response and biocompatibility. Using MWCNTs to build conductive network of sensors, PRV antigen binds specifically to the immunomagnetic microspheres on the sensor, and the resulting immune complex changes the magnetic domain structure of the sensor and the structural gap of MWCNTs, causing the magnetic property and impedance change. TEM and EDS characterization proved that the biosensor was successfully doped with Fe3O4@SiO2-NH2and effectively recognized PRV. Under optimized conditions, the impedance variation was found to be linearly related to the logarithm value of PRV concentrations in the range of 10-1 mg ml-1, with the detection limit of 10 ng ml-1. This paper biosensor demonstrated advantages of portability, high sensitivity and specificity, providing a valuable method for early control of PRV.

A high gauge-factor wearable strain sensor array via 3D printed mold fabrication and size optimization of silver-coated carbon nanotubes.

The development of 3D print technology provided an opportunity to achieve fast and accurate fabrication of wearable sensor arrays. In this paper, high-sensitivity flexible and stretchable silver-coated carbon nanotube (Ag@CNT) wearable strain sensor arrays are fabricated using 3D printing technology and composite nanomaterial synthesis. Ag@CNTs with uniform and compact particles were synthesized with different sizes of carbon nanotubes (CNTs) using a reduction method. Strain sensor arrays were fabricated accurately and efficiently with the aid of 3D printed molds. Sensors with different Ag@CNTs were then compared comprehensively, and it was found that the Ag@CNT (short) sensor, which had a gauge factor (GF) of 62.8 in the 0% to 14.44% stretch range and a GF of 831.3 in the 14.44% to 21.11% stretch range, can significantly enhance the detection of small movements. These wearable strain sensor arrays were utilized in the application of traditional Chinese medicine pulse diagnosis and gesture recognition.

Detection of carcinoembryonic antigen using a magnetoelastic nano-biosensor amplified with DNA-templated silver nanoclusters.

Here we develop a magnetoelastic (ME) nano-biosensor based on the competitive strategy for the detection of a carcinoembryonic antigen (CEA). Specifically, the gold-coated ME material provided a platform and the thiolated single-stranded DNA (HS-DNA) containing a half-complementary sequence towards the CEA aptamer was modified on the surface via Au-S bonding. DNA-templated silver nanoclusters (DNA-AgNCs) containing another half-complementary sequence towards the aptamer were used to amplify the signals by about 2.1 times, compared to those obtained using just the aptamer. CEA aptamers as a bio-recognition element were employed to link HS-DNA and DNA-AgNCs through DNA hybridization. The CEA aptamer preferentially combined with CEA rather than hybridized with DNA. Due to the magnetostrictive nature of the ME materials, the resonant frequency of the nano-biosensor would increase along with the release of DNA-AgNCs and CEA aptamers. The modification process was demonstrated by UV-vis spectra, x-ray photoelectron spectroscopy (XPS), Raman spectroscopy, transmission electron microscope (TEM) and an atomic force microscope (AFM). The nano-biosensor has a linear response to the logarithmic CEA concentrations ranging from 2 pg ml-1 to 6.25 ng ml-1, with a limit of detection (LOD) of 1 pg ml-1 and a sensitivity of 105.05 Hz/ng · ml-1. This study provides a low-cost, highly sensitive and wireless method for selective detection of CEA.

A Novel NiFe2O4/Paper-Based Magnetoelastic Biosensor to Detect Human Serum Albumin.

For the first time, a novel NiFe2O4/paper-based magnetoelastic (ME) biosensor was developed for rapid, sensitive, and portable detection of human serum albumin (HSA). Due to the uniquely magnetoelastic effect of NiFe2O4 nanoparticles and the excellent mechanical properties of the paper, the paper-based ME biosensor transforms the surface stress signal induced by the specific binding of HSA and antibody modified on the paper into the electromagnetic signal. The accumulated binding complex generates a compressive stress on the biosensor surface, resulting in a decrease in the biosensor's static magnetic permeability, which correlates to the HSA concentrations. To improve the sensitivity of the biosensor, the concentration of NiFe2O4 nanofluid and the impregnated numbers of the NiFe2O4 nanofluid-impregnated papers were optimized. The experimental results demonstrated that the biosensor exhibited a linear response to HSA concentrations ranging from 10 µg∙mL-1 to 200 µg∙mL-1, with a detection limit of 0.43 µg∙mL-1, which is significantly lower than the minimal diagnosis limit of microalbuminuria. The NiFe2O4/paper-based ME biosensor is easy to fabricate, and allows the rapid, highly-sensitive, and selective detection of HSA, providing a valuable analytical device for early monitoring and clinical diagnosis of microalbuminuria and nephropathy. This study shows the successful integration of the paper-based biosensor and the ME sensing analytical method will be a highly-sensitive, easy-to-use, disposable, and portable alternative for point-of-care monitoring.

Reversal of TET-mediated 5-hmC loss in hypoxic fibroblasts by ascorbic acid.

Hypoxia resulting in hypoxia-inducible factor-1 alpha (HIF-1α) induction is known to drive scar formation during cutaneous wound healing, and may be responsible for excessive fibrosis inherent to hypertrophic scars and keloids. Because epigenetic pathways play an important role in regulation of fibrosing processes, we evaluated patient scars for DNA hydroxymethylation (5-hydroxymethylcytosine; 5-hmC) status and documented a significant decrease in scar fibroblasts. To test this finding in vitro, human fibroblasts were cultured with cobalt chloride (CoCl2), a known stimulant of HIF-1α. HIF-1α induced so resulted in loss of 5-hmC similar to that seen in naturally occurring scars and was associated with significant downregulation of one of the 5-hmC converting enzymes-ten-eleven translocation 3 (TET3)-as well as increased expression of phosphorylated focal adhesion kinase (p-FAK), which is important in wound contracture. These changes were partially reversed by exposure to ascorbic acid, a recognized epigenetic regulator potentially capable of minimizing excessive scar formation and promoting a more regenerative healing response. Our results provide a novel and translationally relevant mechanism whereby epigenetic regulation of scar formation may be manipulated at the level of fibroblast DNA hydroxymethylation.

Zero-energy-state-oriented tunability of spin polarization in zigzag-edged bowtie-shaped graphene nanoflakes under an electric field.

A comprehensive first-principles study of the correlation between zero-energy states and the tunability of the spin-selective semiconducting properties of zigzag-edged bowtie-shaped graphene nanoflakes under an electric field is presented for the first time. We demonstrate that the spin degenerate semiconducting ground state can be lifted by the electric field. In particular, we find that the number of zero-energy states ('the nullity') defined by the structural configuration determines the complexity and efficiency of the tunability of spin polarization. The fine-tuning of spin-dependent properties by the electric field originates from the manipulation of spin-polarized molecular orbital energies. We expect this study to aid the design of more effective and controllable low-dimensional molecular spintronics.

Rapid cancer diagnosis by highly fluorescent carbon nanodots-based imaging.

Carbon dots (Cdots) with bright green fluorescence were applied to the rapid and selective cell imaging for a variety of cell lines. Different labeling distributions of hepatoma cells (HepG2) and normal human liver cells (LO2) were achieved using Cdots as imaging agents. For HepG2 cells, the Cdots could rapidly permeate the cell membrane and diffuse into the cytoplasm and nucleus within 3 min, and retained their location in the targets for 24 h. However, the Cdots exhibited bright fluorescence only in the cytoplasm of LO2 cell lines. Moreover, the Cdots were almost non-cytotoxic and exhibited superior photostability over a wide range of pH. Therefore, these Cdots have great potential for rapid, luminous and selective bioimaging applications, and are expected to be used as a nucleus-staining agent in cancer diagnosis. Graphical abstract ᅟ.

A fluorometric method for mercury(II) detection based on the use of pyrophosphate-modified carbon quantum dots.

Pyrophosphate-modified carbon quantum dots (PP-CDs) are demonstrated to be a viable fluorescent nanoprobe for mercury(II) (Hg2+) detection. Hg2+ reacts with the pyrophosphate groups on the surface of PP-CDs to form a non-fluorescent complex. This results in quenching of the green fluorescence which has excitation/emission peaks at 400/513 nm. Static quenching is shown to be the dominant mechanism. The probe works in 0.1 µM to 1.4 µM Hg2+ concentration range, and the limit of detection is 2 nM. The PP-CDs were also used to visualize Hg2+ inside human hepatocyte LO2 cells. Graphical abstract Schematic representation of pyrophosphate-modified carbon quantum dots (CDs) for selective and sensitive fluorometric determination of mercury(II). Hg(II) quenches the blue fluorescence of the CDs, and glutathione restores it. The method was used to detect Hg(II) in spiked tap water and inside cells.

AC Electrodeposition of PEDOT Films in Protic Ionic Liquids for Long-Term Stable Organic Electrochemical Transistors.

Poly(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS)-based organic electrochemical transistors (OECTs) are widely utilized to construct highly sensitive biosensors. However, the PSS phase exhibits insulation, weak acidity, and aqueous instability. In this work, we fabricated PEDOT OECT by alternating current electrodeposition in protic ionic liquids. The steady-state characteristics were demonstrated to be stable in long-term tests. In detail, the maximum transconductance, the on/off current ratio, and the hysteresis were stable at 2.79 mS, 504, and 0.12 V, respectively. Though the transient behavior was also stable, the time constant could reach 218.6 ms. Thus, the trade-off between switching speed and stability needs to be considered in applications that require a rapid response.