Stimuli-responsive electrospun nanofibers for drug delivery, cancer therapy, wound dressing, and tissue engineering.

The stimuli-responsive nanofibers prepared by electrospinning have become an ideal stimuli-responsive material due to their large specific surface area and porosity, which can respond extremely quickly to external environmental incitement. As an intelligent drug delivery platform, stimuli-responsive nanofibers can efficiently load drugs and then be stimulated by specific conditions (light, temperature, magnetic field, ultrasound, pH or ROS, etc.) to achieve slow, on-demand or targeted release, showing great potential in areas such as drug delivery, tumor therapy, wound dressing, and tissue engineering. Therefore, this paper reviews the recent trends of stimuli-responsive electrospun nanofibers as intelligent drug delivery platforms in the field of biomedicine.

Ultrafast and On-Demand Oil/Water Separation Membrane System Based on Conducting Polymer Nanotip Arrays.

Ultrafast oil/water separation based on tunable superwettability switch remains a big challenge. Here, inspired by the ultrafast water transport mechanism in sarracenia, we develop a micro/nanostructured porous membrane with conducting polymer nanotip arrays through the surface-initiated polymerizations. By modulating the height (ranging from 49-529 nm) and redox states of nanotips, a smart reversible superwettability switch is facile to obtain with contact angles of water/oil arranging from 161° to about 0°. Besides, liquid transport speed was accelerated more than 1.5 times by increasing the nanotip length. The water flux could reach up to 50326 L m-2 h-1 (1000 times that of a typical industrial ultrafiltration membrane). This is attributed to the stable and continuous water film along the nanotips, which provide a lubrication layer, leading to an increase of permeability. This work provides significant insights into macro/nanostructured membrane design for smart separation, blood lipid filtration, and smart nanoreactors with high permeability.

A Novel Carbon Dots/Thermo-Sensitive In Situ Gel for a Composite Ocular Drug Delivery System: Characterization, Ex-Vivo Imaging, and In Vivo Evaluation.

We developed a potential composite ocular drug delivery system for the topical administration of diclofenac sodium (DS). The novel carbon dot CDC-HP was synthesized by the pyrolysis of hyaluronic acid and carboxymethyl chitosan through a one-step hydrothermal method and then embedded in a thermosensitive in situ gel of poloxamer 407 and poloxamer 188 through swelling loading. The physicochemical characteristics of these carbon dots were investigated. The results of the in vitro release test showed that this composite ocular drug delivery system (DS-CDC-HP-Gel) exhibited sustained release for 12 h. The study of the ex vivo fluorescence distribution in ocular tissues showed that it could be used for bioimaging and tracing in ocular tissues and prolong precorneal retention. Elimination profiles in tears corresponded to the study of ex vivo fluorescence imaging. The area under the curve of DS in the aqueous humor in the DS-CDC-HP-Gel group was 3.45-fold that in the DS eye drops group, indicating a longer precorneal retention time. DS-CDC-HP with a positive charge and combined with a thermosensitive in situ gel might strengthen adherence to the corneal surface and prolong the ocular surface retention time to improve the bioavailability. This composite ocular delivery system possesses potential applications in ocular imaging and drug delivery.

Nanomaterials as photothermal therapeutic agents.

Curing cancer has been one of the greatest conundrums in the modern medical field. To reduce side-effects associated with the traditional cancer therapy such as radiotherapy and chemotherapy, photothermal therapy (PTT) has been recognized as one of the most promising treatments for cancer over recent years. PTT relies on ablation agents such as nanomaterials with a photothermal effect, for converting light into heat. In this way, elevated temperature could kill cancer cells while avoiding significant side effects on normal cells. This theory works because normal cells have a higher heat tolerance than cancer cells. Thus, nanomaterials with photothermal effects have attracted enormous attention due to their selectivity and non-invasive attributes. This review article summarizes the current status of employing nanomaterials with photothermal effects for anti-cancer treatment. Mechanisms of the photothermal effect and various factors affecting photothermal performance will be discussed. Efficient and selective PTT is believed to play an increasingly prominent role in cancer treatment. Moreover, merging PTT with other methods of cancer therapies is also discussed as a future trend.

Bioactive glass functionalized chondroitin sulfate hydrogel with proangiogenic properties.

Blood vessels play an important role in bone defect repair and growth, and a critical challenge of bone defect repair is the promotion of blood vessel formation. Most of the current methods promote vascularization by adding specific growth factors, which are costly and easy to inactivate. In this study, we developed a covalently cross-linked aminated bioactive glass nanoparticle-chondroitin sulfate methacrylate (ABGN-CSMA) organic-inorganic composite hydrogel with angiogenic properties. The amino groups of the ABGNs form covalent bonds with the carboxyl groups on CSMA. Surface amination modification of BGNs not only improved the dispersion of BGNs in CSMA but also significantly improved the mechanical properties of the composite hydrogel. The largest storage modulus (1200 Pa), the largest loss modulus (560 Pa) and the strongest resistance to deformation of the hydrogel are seen at 10% concentration of ABGNs. Simultaneously, the local pH stability and sustained ion release of the composite hydrogel are conducive to cell adhesion, proliferation, and angiogenesis. This work provides evidence for the development of covalently cross-linked organic-inorganic composite hydrogels with angiogenic properties.

A Non-innocent Magnesium Organoclay-Based Drug Vehicle for Improving the Cancer Therapy Effect of Methotrexate.

A synthetic, dispersible magnesium aminoclay (MgAC) was synthesized in the present study. Besides, structural and spectroscopic detections were conducted to investigate the MgAC nanoclay. With a poor aqueous solubility, methotrexate (MTX) has been applied as a valid antitumor agent in recent years. In our research, an unobtrusive sol-gel process was carried out to manufacture the MgAC-MTX nanohybrids through entrapment of MTX over MgAC in situ. The final product was capable of desquamating and thus dispersed in water, equably. In comparison with rough MTX, the MgAC-MTX nanocomposite with a preferable treatment efficacy against MCF-7 cells was mainly attributed to the preeminent enhanced aqueous solubility, controlled release and the increased cellular uptake capacity. Moreover, with excellent anticancer function and hypotoxicity as vindicated in vivo, the MgAC-MTX nanohybrid was supposed to own the potency in the application of malignant tumors cure as a valid nanomedicine. It turned out that, by virtue of its high bioavailability, the MgAC-MTX nanohybrids with high bioavailability is deserving of further study for the treatment of cancers.

Electroactive polymers for tissue regeneration: Developments and perspectives.

Human body motion can generate a biological electric field and a current, creating a voltage gradient of -10 to -90 mV across cell membranes. In turn, this gradient triggers cells to transmit signals that alter cell proliferation and differentiation. Several cell types, counting osteoblasts, neurons and cardiomyocytes, are relatively sensitive to electrical signal stimulation. Employment of electrical signals in modulating cell proliferation and differentiation inspires us to use the electroactive polymers to achieve electrical stimulation for repairing impaired tissues. Electroactive polymers have found numerous applications in biomedicine due to their capability in effectively delivering electrical signals to the seeded cells, such as biosensing, tissue regeneration, drug delivery, and biomedical implants. Here we will summarize the electrical characteristics of electroactive polymers, which enables them to electrically influence cellular function and behavior, including conducting polymers, piezoelectric polymers, and polyelectrolyte gels. We will also discuss the biological response to these electroactive polymers under electrical stimulation. In particular, we focus this review on their applications in regenerating different tissues, including bone, nerve, heart muscle, cartilage and skin. Additionally, we discuss the challenges in tissue regeneration applications of electroactive polymers. We conclude that electroactive polymers have a great potential as regenerative biomaterials, due to their ability to stimulate desirable outcomes in various electrically responsive cells.

Concentration ranges of antibacterial cations for showing the highest antibacterial efficacy but the least cytotoxicity against mammalian cells: implications for a new antibacterial mechanism.

Antibacterial metal ions, such as Ag(+), Zn(2+) and Cu(2+), have been extensively used in medical implants and devices due to their strong broad spectrum of antibacterial activity. However, it is still a controversial issue as to whether they can show the desired antibacterial activity while being toxic to mammalian cells. It is very important to balance their antibacterial effectiveness with minimal damage to mammalian cells. Toward this end, this study is to identify the suitable concentrations of these three ions at which they can effectively kill two types of clinically relevant bacteria (Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli)) but show no obvious cytotoxicity on fibroblasts. Such concentration ranges are found to be 2.5 × 10(-7) M-10(-6) M, 10(-5) M-10(-4) M, and 10(-5) M-10(-4) M for Ag(+), Zn(2+), and Cu(2+), respectively. Investigation of their antibacterial mechanism shows that these three metal ions all show antibacterial property through a mechanism of damaging bacterial cell membranes by the generation of reactive oxygen species but surprisingly preserving the integrity of bacterial genomic DNA. The encouraging results indicate that antibacterial metal ions with controlled concentrations can bring considerable benefits to biomedical applications.

Influence of Surrounding Cations on the Surface Degradation of Magnesium Alloy Implants under a Compressive Pressure.

The effect of cations in the surrounding solutions on the surface degradation of magnesium alloys, a well-recognized biodegradable biomaterial, has been neglected compared with the effect of anions in the past. To better simulate the compressive environment where magnesium alloys are implanted into the body as a cardiovascular stent, a device is designed and employed in the test so that a pressure, equivalent to the vascular pressure, can be directly applied to the magnesium alloy implants when the alloys are immersed in a medium containing one of the cations (K(+), Na(+), Ca(2+), and Mg(2+)) found in blood plasma. The surface degradation behaviors of the magnesium alloys in the immersion test are then investigated using hydrogen evolution, mass loss determination, electron microscopy, pH value, and potentiodynamic measurements. The cations are found to promote the surface degradation of the magnesium alloys with the degree decreased in the order of K(+) > Na(+) > Ca(2+) > Mg(2+). The possible mechanism of the effects of the cations on the surface degradation is also discussed. This study will allow us to predict the surface degradation of magnesium alloys in the physiological environment and to promote the further development of magnesium alloys as biodegradable biomaterials.

Magnesium with micro-arc oxidation coating and polymeric membrane: an in vitro study on microenvironment.

Numerous modification methods have been reported to enhance the corrosion resistance of magnesium with positive results. However, little attention has been paid on their impact on micro-environment, particularly the ion concentration and local pH value. In this study, two different coatings were prepared on magnesium, one with porous micro-arc oxidation (MAO) coating alone, and the other with additional polymer polyhydroxybutyrate (PHB) membrane using spinning technique. Their in vitro corrosional and biological behaviors were investigated and compared. Both coatings were found to reduce the degradation rate of magnesium, but an additionally deposited PHB membrane was superior to MAO-coated magnesium since it could produce a micro-environment with preferable local pH value and ion concentration for osteoblast proliferation. Our study suggests that micro-environment should be another critical issue in evaluation of a modification method for orthopaedic implants.

Taurine-induced fabrication of nano-architectured conducting polypyrrole on biomedical titanium.

In this article, taurine, one of the small biomolecules associated with bone metabolism, is firstly utilized to induce the fabrication of nano-architectured conducting polypyrrole (NCPPy) on biomedical titanium in diverse pH values of phosphate buffer solution (PBS). Accordingly, the possible mechanism for the fabrication of NCPPy is proposed, which is dependent on the states of polytaurine from the polymerization of taurine, i.e., the inability of forming polytaurine and unordered restricted space results in taurine-incorporated and polytaurine-incorporated tightly packed nanoparticles (pH 6.2 and 8.0), respectively, and however, ordered restricted space constructed by polytaurine chains induces the fabrication of polytaurine-incorporated nanopillars (pH 6.8) and polytaurine-incorporated nanowire networks (pH 7.4).

Cell-laden photocrosslinked GelMA-DexMA copolymer hydrogels with tunable mechanical properties for tissue engineering.

To effectively repair or replace damaged tissues, it is necessary to design three dimensional (3D) extracellular matrix (ECM) mimicking scaffolds with tunable biomechanical properties close to the desired tissue application. In the present work, gelatin methacrylate (GelMA) and dextran glycidyl methacrylate (DexMA) with tunable mechanical and biological properties were utilized to prepared novel bicomponent polymeric hydrogels by cross-linking polymerization using photoinitiation. We controlled the degree of substitution (DS) of glycidyl methacrylate in DexMA so that they could obtain relevant mechanical properties. The results indicated that copolymer hydrogels demonstrated a lower swelling ratio and higher compressive modulus as compared to the GelMA. Moreover, all of the hydrogels exhibited a honeycomb-like architecture, the pore sizes decreased as DS increased, and NIH-3T3 fibroblasts encapsulated in these hydrogels all exhibited excellent viability. These characteristics suggest a class of photocrosslinkable, tunable mechanically copolymer hydrogels that may find potential application in tissue engineering and regenerative medicine applications.

Controlled oxidative nanopatterning of microrough titanium surfaces for improving osteogenic activity.

To further enhance the biological properties of acid-etched microrough titanium surfaces, titania nanotextured thin films were produced by simple chemical oxidation, without significantly altering the existing topographical and roughness features. The nanotextured layers on titanium surfaces can be controllably varied by tuning the oxidation duration time. The oxidation treatment significantly reduced water contact angles and increased the surface energy compared to the surfaces prior to oxidation. The murine bone marrow stromal cells (BMSCs) were used to evaluate the bioactivity. In comparison, oxidative nanopatterning of microrough titanium surfaces led to improved attachment and proliferation of BMSCs. The rate of osteoblastic differentiation was also represented by the increased levels of alkaline phosphatase activity and mineral deposition. These data indicated that oxidative nanopatterning enhanced the biological properties of the microrough titanium surfaces by modulating their surface chemistry and nanotopography. Based on the proven mechanical interlocking ability of microtopographies, enhancement of multiple osteoblast functions attained by this oxidative nanopatterning is expected to lead to better implant osseointegration in vivo.

Reversibly controlling preferential protein adsorption on bone implants by using an applied weak potential as a switch.

A facile method is needed to control the protein adsorption onto biomaterials, such as, bone implants. Herein we doped taurocholic acid (TCA), an amphiphilic biomolecule, into an array of 1D nano-architectured polypyrrole (NAPPy) on the implants. Doping TCA enabled the implant surface to show reversible wettability between 152° (superhydrophobic, switch-on state) and 55° (hydrophilic, switch-off state) in response to periodically switching two weak electrical potentials (+0.50 and -0.80 V as a switch-on and switch-off potential, respectively). The potential-switchable reversible wettability, arising from the potential-tunable orientation of the hydrophobic and hydrophilic face of TCA, led to potential-switchable preferential adsorption of proteins as well as cell adhesion and spreading. This potential-switchable strategy may open up a new avenue to control the biological activities on the implant surface.

Tough, Antifreezing, and Piezoelectric Organohydrogel as a Flexible Wearable Sensor for Human-Machine Interaction.

Piezoelectric hydrogel sensors are becoming increasingly popular for wearable sensing applications due to their high sensitivity, self-powered performance, and simple preparation process. However, conventional piezoelectric hydrogels lack antifreezing properties and are thus confronted with the liability of rupture in low temperatures owing to the use of water as the dispersion medium. Herein, a kind of piezoelectric organohydrogel that integrates piezoelectricity, low-temperature tolerance, mechanical robustness, and stable electrical performance is reported by using poly(vinylidene fluoride) (PVDF), acrylonitrile (AN), acrylamide (AAm), p-styrenesulfonate (NaSS), glycerol, and zinc chloride. In detail, the dipolar interaction of the PVDF chain with the PAN chain facilitates the crystal phase transition of PVDF from the α to ß phase, which endows the organohydrogels with a high piezoelectric constant d33 of 35 pC/N. In addition, the organohydrogels are highly ductile and can withstand significant tensile and compressive forces through the synergy of the dipolar interaction and amide hydrogen bonding. Besides, by incorporating glycerol and zinc chloride, the growth of ice crystals is inhibited, allowing the organohydrogels to maintain stable flexibility and sensitivity even at -20 °C. The real-time monitoring of the pulse signal for up to 2 min indicates that the gel sensor has stable sensitivity. It is believed that our organohydrogels will have good prospects in future wearable electronics.

Nanostructured conducting polymers as intelligent implant surface: fabricated on biomedical titanium with a potential-induced reversible switch in wettability.

Conducting polypyrrole (PPy) nanotube arrays, nanotube networks and irregular films are deposited on biomedical titanium. By in situ application of weak periodic potentials, the nanostructured conducting polymers undergo a reversible switch in wettability, which is a redox process of dopant molecules (as hydrophilic groups) immobilized and de-immobilized on the surface of the conducting polymers.

Silk Fibroin Combined with Electrospinning as a Promising Strategy for Tissue Regeneration.

The development of tissue engineering scaffolds is of great significance for the repair and regeneration of damaged tissues and organs. Silk fibroin (SF) is a natural protein polymer with good biocompatibility, biodegradability, excellent physical and mechanical properties and processability, making it an ideal universal tissue engineering scaffold material. Nanofibers prepared by electrospinning have attracted extensive attention in the field of tissue engineering due to their excellent mechanical properties, high specific surface area, and similar morphology as to extracellular matrix (ECM). The combination of silk fibroin and electrospinning is a promising strategy for the preparation of tissue engineering scaffolds. In this review, the research progress of electrospun silk fibroin nanofibers in the regeneration of skin, vascular, bone, neural, tendons, cardiac, periodontal, ocular and other tissues is discussed in detail.

All-Polymer Piezoelectric Elastomer with High Stretchability, Low Hysteresis, Self-Adhesion, and UV-Blocking as Flexible Sensor.

All-polymer piezoelectric elastomers that integrate self-powered, soft, and elastic performance are attractive in the fields of flexible wearable electronics and human-machine interfaces. However, a lack of adhesion and UV-blocking performances greatly hinders the potential applications of elastomers in these emerging fields. Here, a high-performance piezoelectric elastomer with piezoelectricity, mechanical robustness, self-adhesion, and UV-resistance was developed by using poly(vinylidene fluoride) (PVDF), acrylonitrile (AN), acrylamide (AAm), and oxidized tannic acid (OTA) (named PPO). In this design, the dipole-dipole interactions between the PVDF and PAN chains promoted the content of ß-PVDF, endowing high piezoelectric coefficient (d33, 58 pC/N). Besides, high stretchability (∼500%), supercompressibility (∼98%), low Young's modulus (∼0.02 MPa), and remarkable elasticity (∼13.8% hysteresis ratio) were achieved simultaneously for the elastomers. Inspired by the mussel adhesion chemistry, the OTA containing abundant catechol and quinone groups provided high adhesion (93.26 kPa to wood) and an exceptional UV-blocking property (∼99.9%). In addition, the elastomers can produce a reliable electric signal output (Vocmax = 237 mV) and show a fast response (24 ms) when subjected to external force. Furthermore, the elastomer can be easily assembled as a wearable sensor for human physiological (body pulse and speech identification) monitoring and communication.

Soft, Super-Elastic, All-Polymer Piezoelectric Elastomer for Artificial Electronic Skin.

Piezoelectric sensors are widely used in wearable devices to mimic the functions of human skin. However, it is considerably challenging to develop soft piezoelectric materials that can exhibit high sensitivity, stretchability, super elasticity, and suitable modulus. In this study, a soft skin-like piezoelectric polymer elastomer composed of poly(vinylidene fluoride) (PVDF) and a novel elastic substrate polyacrylonitrile is prepared by combining the radical polymerization and freeze-drying processes. Dipole-dipole interaction results in the phase transition of PVDF (α phase to ß phase), which enhances the electrical and mechanical performances. Thus, we achieve a high piezoelectric coefficient (d33max = 63 pC/N), good stretchability (211.3-259.3%), super compressibility (subjected to 99% compression strain without cracking), and super elasticity (100% recovery after extreme compression) simultaneously for the elastomer. The soft composite elastomer produces excellent electrical signal output (Vocmax = 253 mV) and responds rapidly (15 ms) to stress-induced polarization effects. In addition, the elastomer-based sensor accurately detects various physiological signals such as gestures, throat vibrations, and pulse waves. The developed elastomers exhibit excellent mechanical properties and high sensitivity, which helps facilitate their application as artificial electronic skin to sense subtle external pressure in real time.

Microenvironment-responsive Cu-phenolic networks coated nanofibrous dressing with timely macrophage phenotype transition for chronic MRSA infected wound healing.

Methicillin-resistant Staphylococcus aureus (MRSA) infection is a pressing clinical issue that impedes wound healing. Pro-inflammatory M1 macrophages is required to clear bacteria and recruit various cell types during the initial phase of wound healing, but timing of this process is crucial. Herein, a microenvironment-responsive nanofibrous dressing capable of timely macrophage phenotype transition in vivo is constructed by coating copper ions (Cu2+)-polydopamine (PDA) networks on poly (ε-caprolactone) fiber (PCL-fiber) membrane. During the initial post-implantation period, the nanofibrous dressing show pH-sensitive Cu2+ release in the acidic infection microenvironment. The release Cu2+ have a direct killing effect on MRSA, and promote the proinflammatory M1 phenotype of macrophages to enhance the antibacterial macrophage response. Later, PDA to become a reactive oxygen species (ROS) scavenger when in microenvironments with elevated ROS levels, which conferred the dressing with an immunomodulatory activity that convert M1 macrophages into M2 macrophages. In vivo examination in an MRSA infected full-thickness skin wounds of rat model demonstrates that this dressing significantly facilitated infection eradication and wound healing through modulating local inflammatory phenotype. Overall, this study offers a simple and effective approach for timely manipulation of inflammation progression to promote infected wound healing.