Tunable Mechanical Strength Research Articles

Nacre-inspired layered composite gels with broad tunable mechanical strength and structural color for stress visualization.

The brick-and-mortar architecture of nacre shells brings radiant structural colors, high toughness, and strength, inspiring numerous designs for structural and optical materials. However, constructing structural color is not always easy, especially among soft materials where aligning components against random and dynamically active environments is generally difficult. Here, we propose a composite organohydrogel capable of visualizing multiple levels of stress, featuring broad tunable mechanical properties, dynamic mechanochromism, deep low working temperatures, and anti-drying attributes. In the composite gels, the intercalation between α-zirconium phosphate (α-ZrP) nanoplates and poly-(diacetone acrylamide-co-acrylamide) is induced by shear-orientation-assisted self-assembly followed by solvent replacement. The highly tailorable (from ∼780 nm to ∼445 nm) range of colors was achieved by regulating the concentration of α-ZrP and glycerol inside the matrix. With the help from glycerol, the composite gels exhibited long-term stability (7 d) in the arid condition and remarkable low-temperature tolerance (-80 °C). The extraordinary mechanical property (compressive strength up to 119 MPa) of composite gels is achieved by the assembled α-ZrP plates with a small aspect ratio, high negative charge repulsion, and abundant hydrogen bonding sites. As a result, the mechanochromic sensor based on the composite gel enjoys a wide range of stress detection (0-1862 KPa). This study provides a new strategy for constructing high strength structural-colored gels, opening up opportunities for sensitive yet strong mechanochromic sensors in extreme environments.

Thermo-Responsive Nanocomposite Bioink with Growth-Factor Holding and its Application to Bone Regeneration.

Three-dimensional (3D) bioprinting, which is being increasingly used in tissue engineering, requires bioinks with tunable mechanical properties, biological activities, and mechanical strength for in vivo implantation. Herein, a growth-factor-holding poly(organophosphazene)-based thermo-responsive nanocomposite (TNC) bioink system is developed. The mechanical properties of the TNC bioink are easily controlled within a moderate temperature range (5-37°C). During printing, the mechanical properties of the TNC bioink, which determine the 3D printing resolution, can be tuned by varying the temperature (15-30°C). After printing, TNC bioink scaffolds exhibit maximum stiffness at 37°C. Additionally, because of its shear-thinning and self-healing properties, TNC bioinks can be extruded smoothly, demonstrating good printing outcomes. TNC bioink loaded with bone morphogenetic protein-2(BMP-2) and transforming growth factor-beta1 (TGF-β1), key growth factors for osteogenesis, is used to print a scaffold that can stimulate biological activity. A biological scaffold printed using TNC bioink loaded with both growth factors and implanted on a rat calvarial defect model reveals significantly improved bone regenerative effects. The TNC bioink system is a promising next-generation bioink platform because its mechanical properties can be tuned easily for high-resolution 3D bioprinting with long-term stability and its growth-factor holding capability has strong clinical applicability.

Recent Advancement of Functional Hydrogels toward Diabetic Wound Management.

Wound healing is a dynamic, orchestrated process comprising partially overlapping phases of hemostasis, inflammation, proliferation, and remodeling. This programmed process, dysregulated in diabetic individuals, results in chronic diabetic wounds. The normal process of healing halts at the inflammatory stage, and this prolonged inflammatory phase is characteristic of diabetic wounds. There are a few U.S. Food & Drug Administration approved skin substitutes; dermal matrixes are commercially available to manage diabetic wounds. However, expensiveness and nonresponsiveness in a few instances are the major limitations of such modalities. To address the issues, several treatment strategies have been exploited to treat chronic wounds; among them hydrogel-based systems showed promise due to favorable properties such as excellent absorption capabilities, porous structure, tunable mechanical strength, and biocompatibility. In the past two decades, hydrogels have become one of the most acceptable systems in the field of wound dressing material, offering single functionality to multifunctionality. This review focuses on the advancement of functional hydrogels explored for diabetic wound management. The process of diabetic wound healing is discussed in the light of the normal healing process, and the role of macrophages in the process is explained. This review also discusses the different approaches to treat diabetic wounds using functional hydrogels, along with their future opportunities.

3D-printed cardiovascular polymer scaffold reinforced by functional nanofiber additives for tunable mechanical strength and controlled drug release

Controlled drug eluting cardiovascular scaffolds (CDECS) have received significant interest in human healthcare compared to conventional drug eluting cardiovascular scaffolds (DECS) owing to their improved efficiency, patient compliance, and reduced toxicity. However, experimental demonstration of CDECS using synthetic polymers have had minimal success to yet. Herein, we proposed the use of gold particles incorporated carbon nanofibers (Au-S-CNF; hereafter referred to as functional additives) that are capable of reinforcing polycaprolactone (PCL) cardiovascular scaffolds and facilitating controlled drug delivery. The incorporation of 0.5 wt% of the designed functional additives uniformly dispersed in PCL matrix and cause superior mechanical properties (elastic modulus, 169 MPa and toughness, 334 J cm−3) to that of bare PCL scaffolds. The functional additives reinforced PCL composites are used to fabricate patient specific CDECS using a 3-dimensonal (3D) printing technique. The practical feasibility of the proposed CDECS is established by demonstrating the scaffold's visibility in a mouse thoracic cavity using real-time X-ray imaging. Finally, the functional additives reinforced PCL cardiovascular scaffold used as a DECS and on-demand CDECS triggered by a near infrared (NIR) light source. This proposed medical device has the great potential to be employed for targeted therapies such as atherosclerosis, cancer, and tissue engineering.

Porous Silicon Microneedles for Enhanced Transdermal Drug Delivery

AbstractThe transdermal route is attractive for the minimally invasive administration of small and large molecules. Microneedles (MNs) are particularly promising because of their straightforward, cost‐effective, and safe administration. But precise control over their degradation rate within the skin remains a challenge. Here, porous silicon microneedles (pSi MNs) with controlled degradation rate, tunable porosity, high payload capacity, and mechanical stability are introduced for transdermal delivery of bioactive molecules. pSi MNs are fabricated by combining dry and wet etching methods. After creating MNs via deep reactive ion etching, a porous surface is obtained by electrochemical anodization, producing pSi MNs of about 42 µm length, tip diameter < 1 µm, and conformal porous layers. The biodegradability and the mechanical properties of pSi MNs are adjusted by changing the thickness of the porous layer from 1.5 to 4.0 µm. Both small and macromolecular drug molecules are uniformly loaded into the porous layer of the pSi MN arrays. Ex vivo penetration experiments on porcine tissue demonstrate efficient transdermal delivery using pSi MNs. The novel pSi MNs with tunable porosity, biodegradability, and mechanical strength offer opportunities for the delivery of biotherapeutics through the skin, engendering innovations in pharmaceutical sciences.

A Shapable Alginate Hydrogel Resolving the Conflicts between Multifunctionality and Fabrication Simplicity.

Alginate is a naturally derived biocompatible polymer widely used as a drug or food adjuvant. However, its usage as a biofunctional material has been confounded by the lack of shapable strategies. In this study, we report an easily applied ionic cross-linking strategy for fabricating shapable multifunctional SA-Ca(II) hydrogels employing the process of regulated diffusion. The fabrication proceeds in neutral solutions under ambient conditions. The obtained SA-Ca(II) hydrogel presents tunable moduli ranging from 4 to 30 kPa, resembling a series of human tissues. The tunable mechanical strength provides differentiation signals for stem cell polarization. The hydrogel film can lift a weight of 10 kg. The hydrogel can be prepared into various shapes and remains stable over one year upon rinsing in deionized water, but rapidly degrades in alginate lyase solutions. Subcutaneously embedded SA-Ca(II) hydrogels in mice show high biocompatibility and degrade over 4 weeks accompanied by hair follicle regeneration. Wearable protections as well as stimuli-responsive electronic circuits are then achieved, which not only protect the model body against high-temperature environments but also show warning signals when the protection loses effectiveness because of high temperatures. Overall, these results demonstrate that our SA-Ca(II) hydrogel offers appealing comprehensive functionalities from multifaceted perspectives, including mechanical strength, economic and environmental considerations, transparency, forming capability, biocompatibility, and conductivity.

Microstructure characterization and enhanced mechanical properties of quasi-continuous network structured Ti3AlC2-Al3Ti/2024Al composite

Al matrix composites (AMCs) with high specific strength are highly desirable for a wide range of critical applications due to their unique mechanical and electrical characteristics. On the target of the effective production of high-performance AMCs, a novel quasi-continuous network structure based on Ti3AlC2 was devised rationally and developed a heterogeneous Ti3AlC2-Al3Ti synergistically reinforced 2024 Al composites by the technique of reactive hot press. Herein, the produced Ti3AlC2-Al3Ti/2024Al composite exhibited superior mechanical strength, importantly, it exhibits a minimal ductility reduction in comparison with pure 2024Al. Compressive yield strength, tensile ultimate and yield strength along with bending strength increased with the increasing Ti3AlC2 content; the optimal values for 5vol%Ti3AlC2/2024Al composite were increased by 16.9% in compressive yield strength, 11.5% in UTS and 30.0% in YTS compared with 2024Al. The mechanical properties increment was attributed to the synergistic effect of the quasi- network structure, dispersion strengthening, load transfer strengthening and thermal mismatch strengthening mechanism. The approach reported in this study is expected to open new avenues for advanced AMCs synthesis with tunable morphology and mechanical strength for their widespread applications.

Fabrication of cancellous-bone-mimicking β-tricalcium phosphate bioceramic scaffolds with tunable architecture and mechanical strength by stereolithography 3D printing

It is highly challenging to fabricate bioceramic scaffolds mimicking architecture and mechanical strength of cancellous bone. Gyroid structure, which is based on triply periodic minimal surface, highly resembles the architecture of cancellous bone. Herein, β-tricalcium phosphate (β-TCP) bioceramic scaffolds with gyroid structure were fabricated by stereolithography (SLA) 3D printing. The SLA 3D printing ensured high precision of ceramic part. The porosity (51–87%), pore size (250 – 2400 µm), pore wall thickness (< 300 µm) and compressive strength (0.6 – 16.8 MPa) of gyroid bioceramic scaffolds were readily adjusted to match various sites of cancellous bone. The gyroid bioceramic scaffolds were more favorable for cell proliferation than the grid-like bioceramic scaffolds. The cancellous-bone-mimicking gyroid bioceramic scaffolds with tunable architecture and mechanical strength were expected to efficiently repair the target bone defects.

Manufacturing of self-standing multi-layered 3D-bioprinted alginate-hyaluronate constructs by controlling the cross-linking mechanisms for tissue engineering applications

Three-dimensional (3D) bioprinting of self-supporting stable tissue and organ structure is critically important in extrusion-based bioprinting system, especially for tissue engineering and regenerative medicine applications. However, the development of self-standing bioinks with desired crosslinking density, biocompatibility, tunable mechanical strength and other properties like self-healing, in situ gelation, drug or protein incorporation is still a challenge. In this study, we report a hydrogel bioink prepared from alginate (Alg) and hyaluronic acid (HA) crosslinked through multiple crosslinking mechanisms, i.e. acyl-hydrazone, hydrazide interactions and calcium ions. These Alg-HA gels were highly dynamic and shear-thinning with exceptional biocompatibility and tunable mechanical properties. The increased dynamic nature of the gels is mainly chemically attributed to the presence of acyl-hydrazone bonds formed between the amine groups of the acyl-hydrazide of alginate and the monoaldehyde of the HA. Among the different combinations of Alg-HA gel compositions prepared, the A5H5 (Alginate-acyl-hydrazide:HA-monoaldehyde, ratio 50:50) gel showed a gelation time of ∼60 s, viscosity of ∼400 Pa s (at zero shear rate), high stability in various pH solutions and increased degradation time (>50 days) than the other samples. The A5H5 gels showed high printability with increased post-printing stability as observed from the 3D printed structures (e.g. hollow tube (∼100 layers), porous cube (∼50 layers), star, heart-in, meniscus and lattice). The scanning electron microscopy analysis of the 3D constructs and hydrogels showed the interconnected pores (∼181 µm) and crosslinked networks. Further, the gels showed sustained release of 5-amino salicylic acid and bovine serum albumin. Also, the mechanical properties were tuned by secondary crosslinking via different calcium concentrations. In vitro assays confirmed the cytocompatibility of these gels, where the 3D bioprinted lattice and tubular (∼70 layers) constructs demonstrated high cell viability under fluorescence analysis. In in vivo studies, Alg-HA gel showed high biocompatibility (>90%) and increased angiogenesis (threefolds) and reduced macrophage infiltration (twofold decrease), demonstrating the promising potential of these hydrogels in 3D bioprinting applications for tissue engineering and regenerative medicine with tunable properties.

Organic solvent vapor/thermal responsive binary gels with tunable transparency and mechanical strength

In this work, we illustrate the fabrication of binary gels via self-sorting assembly between β-cyclodextrin and the second gelators, which show significant transparency changes responsive to the solvent vapor and temperature. The mixing of β-cyclodextrin and clay minerals in the mixture of dimethylformamide and water produced opaque gels. After exposed to specific solvent environments, the light transmittance of opaque gels was greatly enhanced ascribed to the host-guest complexation between β-cyclodextrin and organic solvent vapors. Toluene, xylene, tetrahydrofuran, dioxane and pyridine aroused gel fiber to bulky crystal transformation, which also slightly enhanced the mechanical strength of the binary gels. In addition, the gelator could be expanded to organic gelator like folic acid. This work offers a feasible way to fabricate soft gel composites that show transparency changes responsive to solvent vapors.

Advanced 3D-Printing Bioinks for Articular Cartilage Repair.

Chondral lesions caused by stressors, such as injury or inflammation, lead to osteoarthritis (OA). OA is a degenerative joint disease that has become a challenge worldwide. As the articular cartilage is incapable of self-regeneration due to the absence of vessels and nerves, novel cartilage repair techniques are urgently needed. Three-dimensional (3D) bioprinting, which allows the precise control of internal architecture and geometry of printed scaffolds, has stepped up to be a promising strategy in cartilage restoration. With regards to 3D bioprinting, bioinks with proper chemical and mechanical properties play one of the most critical roles in designing successful cartilage tissue constructs. In particular, hydrogels as 3D hydrophilic cross-linked polymer networks are highly recommended as bioinks because of their fine biocompatibility, easy fabrication, and tunable mechanical strength. Herein, we highlight the widely used polymers for hydrogel preparation and further provide a non-exhaustive overview of various functional modified additives (such as cells, drugs, bioactive factors and ceramic) to exploit the unique properties suitable for bioprinted cartilage. Finally, a prospective on future development for 3D-bioprinting in cartilage repair is elucidated in this review.

Cooperative Metal Ion Coordination to the Short Self-Assembling Peptide Promotes Hydrogelation and Cellular Proliferation.

Noncovalent interactions among short peptides and proteins lead to their molecular self-assembly into supramolecular packaging, which provides the fundamental basis of life. These biomolecular assemblies are highly susceptible to the environmental conditions, including temperature, light, pH, and ionic concentration, and thus inspiring the fabrication of a new class of stimuli-responsive biomaterials. Here, for the first time the cooperative effect of the divalent metal ions to promote hydrogelation in the short collagen inspired self-assembling peptide for developing advanced biomaterials is reported. Introduction of the biologically relevant metal ions (Ca2+ /Mg2+ ) to the peptide surpasses its limitation to self-assemble into a multiscale structure at physiological pH. In particular, in presence of metal ions, the negatively charged peptide shows a distinct shift in its equilibrium point of gelation and demonstrates conversion from sol to gel and thus enabling the scope of fabricating an advanced biomaterial for controlling cellular behavior. Interestingly, tunable mechanical strength and improved cellular response are observed within ion-coordinated peptide hydrogels compared to the peptide gelator. Microscopic analyses, rheological assessment, and biological studies establish the importance of utilizing a novel strategy by simply using metal ions to modulate the physical and biological attributes of collagen inspired peptide (CIPs) to construct next-generation biomaterials.

Bright, noniridescent structural coloration from clay mineral nanosheet suspensions.

Structural colors originate by constructive interference following reflection and scattering of light from nanostructures with periodicity comparable to visible light wavelengths. Bright and noniridescent structural colorations are highly desirable. Here, we demonstrate that bright noniridescence structural coloration can be easily and rapidly achieved from suspended two-dimensional nanosheets of a clay mineral. We show that brightness is enormously improved by using double clay nanosheets, thus optimizing the clay refractive index that otherwise hampers structural coloration from such systems. Intralayer distances, and thus the structural colors, can be precisely and reproducibly controlled by clay concentration and ionic strength independently, and noniridescence is readily and effortlessly obtained in this system. Embedding such clay-designed nanosheets in recyclable solid matrices could provide tunable vivid coloration and mechanical strength and stability at the same time, thus opening a previously unknown venue for sustainable structural coloration.

Poly(ether ester) and related block copolymers via organocatalytic ring‐opening polymerization

AbstractPoly(p‐dioxanone) (PPDO) produced by ring‐opening polymerization (ROP) ofp‐dioxanone (PDO) has been attracted intensive attention in bioengineering and environmental materials due to the coexistence of ester and ether bonds in the repeating units. Herein, we systematically study the ROP behavior of PDO using classical organic amidine and guanidine compounds. The cyclic and linear PPDO homopolymers are efficiently produced and confirmed by the combination of1H,13C NMR and MALDI‐TOF MS spectra. Furthermore, triblock copolymers (PPDO‐b‐PCL‐b‐PPDO) containing poly(ε‐caprolactone) (PCL) as the soft segment and PPDO as the hard segment are prepared in the presence of ethylene glycol. The resultant block copolymers are well characterized using NMR, gel permeation chromatography, differential scanning calorimetry, and thermogravimetric analysis. It is found that the prepared triblock copolymers exhibit tunable flexibility, stabilization, hydrophilicity, and mechanical strength, which could be used as thermoplastic materials in biological and tissue engineering areas.

Shape memory poly (ether ether ketone)s with tunable chain stiffness, mechanical strength and high transition temperatures

ABSTRACT Shape memory polymers, with intrinsic enhanced strength and high thermal stability, are highly demanded in aerospace, engineering manufacturing, and spatial structures. In this paper, we develop a series of thermoplastic shape memory poly(ether ether ketone)s (PEEKs) for the first time, achieving an excellent shape memory ability, high strength, and great thermal stability via a condensation polymerization. Through tuning the proportion of different bisphenol monomers, the flexibility of molecular main chains is adjusted, resulting in the regulation of transition temperature and mechanical performances. Synthesized PEEKs possess the tunable Tg from 143.3°C to 178.6°C, the enhanced tensile strength from 48.4 to 65.1 MPa, and Young’s modulus from 0.45 to 1.8 GPa, in addition to the excellent heat-triggered shape memory effect, as indicated by high recovery ratio (94%–98.9%) and fixity ratio (over 99.5%). Furthermore, after incorporating the magnetocaloric Fe3O4 particles, the composites exhibit remotely noncontact magnetic-triggered shape memory behaviors (Fe3O4 content over 10 wt%). These synthesized Tg tunable shape memory PEEKs and the composites have wide utilization potential in fields of engineering and aerospace structures, owing to the excellent mechanical properties, thermal stability, unique programmable deformation ability, and remote actuation.

Novel polyurethane foams with titanium powder and collagen for medical uses

In this study, we aimed to develop a novel soy-based polyurethane (PU) foam material reinforced with titanium powder and collagen for use in bone tissue engineering. In this context, soy polyol-based PU foams having different (5, 10, 20 wt%) concentrations of recycled titanium powders and hydrolyzed collagen (1 wt%) were prepared and characterized by scanning electron microscopy, water contact angle measurement, and compression tests. Biocompatibility was determined by cytotoxicity analysis. It was observed that PU foams with different titanium and collagen concentrations can have optimized mechanical strength, biocompatibility, chemical composition, and morphology that resemble porous bone texture-like structure. The compressive strength of PU foam increased by 72.6% with the inclusion of 20 wt% titanium powder and slightly decreased by 9.4% with 1 wt% collagen. Cytotoxicity results revealed that PU foam with the synergistic combination of titanium powder and collagen had higher biocompatibility compared to control sample. To our knowledge, this novel biocomposite material, developed the first time in literature by incorporation of medical grade titanium powder and hydrolyzed collagen into soy-based PU matrix, has many advantages such as tunable mechanical strength, biocompatibility, low cost, and easy processability.

Development of Silk Fibroin Scaffolds by Using Indirect 3D-Bioprinting Technology.

Due to the excellent biocompatibility of natural polymers, a variety of natural polymers have been widely used as biomaterials for manufacturing tissue engineered scaffolds. Despite the excellent biological activity of natural polymers, there have been obstacles in using them on their own to prepare 3D scaffolds with sufficient mechanical strength. Although multiple 3D-bioprinting technologies have recently emerged as effective manufacturing tools for scaffold preparation, scaffold preparation using only natural polymers with tunable mechanical properties is still difficult. Herein, we introduce novel scaffold fabrication methods using the natural polymer silk fibroin via indirect 3D-bioprinting technology. The developed silk fibroin scaffolds showed biocompatibility and tunable mechanical strength by changing the concentration of the silk fibroin. Furthermore, controlling the flexibility of the silk fibroin scaffolds was made possible by changing the solvent for the silk fibroin solution used to fabricate the scaffold. Consequently, silk fibroin scaffolds fabricated via our method can be considered for various applications in the bioengineering of either soft or musculoskeletal tissues.

Freeze-thaw and solvent-exchange strategy to generate physically cross-linked organogels and hydrogels of curdlan with tunable mechanical properties

Physical gels from natural polysaccharides present the advantage of no toxic cross-linking agents and no chemical modification during preparation. Herein, novel physical gels, transparent organogels and opaque hydrogels from the microorganism-derived (1,3)-β-D-glucan of curdlan were prepared in dimethyl sulfoxide (DMSO) using the freeze-thaw technique, followed by a solvent-exchange strategy with water. The mechanical and structural properties of these gels were investigated by rheology, scanning electron microscopy, attenuated total reflection infrared spectroscopy, wide-angle X-ray diffraction and small-angle X-ray scattering. Gelation mechanisms and intermolecular interaction models have also been proposed. The good solvent DMSO serves as both a crosslinker and a pore-foaming agent in organogels. The reversible macromolecular conformation changes and phase separation of curdlan endow the gels with reversible transparency, volume change and tunable mechanical strength. The new design strategy of facile preparation and performance tuning provides a platform for developing new organogels and sterile hydrogels of curdlan.

Bioinspired, injectable, tissue-adhesive and antibacterial hydrogel for multiple tissue regeneration by minimally invasive therapy

Hemorrhage and wound infection after soft tissue trauma are the main factors causing casualties in surgical procedures and disasters. Currently available tissue adhesives for hemorrhage and wound infection treatment remain unsatisfactory due to the lack of ideal adhesive hydrogels that can integrate injectability, tunable mechanical strength, matching irregular defect and antibacterial property into one system. Here, inspired by the mussel adhesive protein and the natural extracellular matrix (ECM) composition, we engineered a gelatin-based adhesive hydrogel (Dopamine modified methacrylate gelatin, GMDA) with strong tissue adhesiveness and antibacterial property. This bioinspired injectable hydrogel demonstrated tunable mechanical properties and optimal elasticity due to the double-crosslinked network formed through the horseradish peroxidase (HRP) / hydrogen peroxide (H2O2) and ultraviolet (UV) light crosslinking. In addition, these adhesive hydrogels could withstand up to 250 mmHg blood pressure (significantly higher than normal blood pressure, systolic BP 60–160 mmHg) and showed superior hemostasis capability of uncontrolled bleeding in vivo. Most importantly, the hydrogel exhibited significant antibacterial property because of the released residual H2O2 after hydrogel formation. Further in vivo studies demonstrated that the hydrogel loaded with epidermal growth factor (EGF) could promote efficient skin regeneration with the formation of skin appendages. These findings shed new light on developing a multifunctional bioinspired adhesive hydrogel that could serve as a promising biomaterial for hemostasis and wound infection treatment and other minimally invasive use of biomedical applications.

A variable stiffness adhesive enabled by joule heating effect

Smart adhesives have attracted great attention due to their reversible adhesion capacities and stimuli-responsive adhesion behavior. However, for most reported smart adhesive materials, it remains challenging to combine high conductivity, tunable adhesion, thermal healing, tunable mechanical strength, recyclability and reusability into one material. Herein, a new smart adhesive material composed of supramolecular polymer and graphene nanoplates was successfully designed and prepared. Strong and recycle adhesion performance was realized on various surfaces, with a maximum adhesion strength of 6.48 MPa on glass. In addition to excellent adhesion recyclability and reusability, this composite adhesive exhibits high mechanical strength, excellent plasticity and thermal healing properties. Through Joule heating effects, we can not only switch the adhesive between on and off states, but also tune the adhesion strength in a wide range. Based on these features, we designed a simple electric gripper which can raise and drop various objects simply by changing the applied voltages.