Phytic Acid Maintains Peripheral Neuron Integrity and Enhances Survivability against Platinum-Induced Degeneration via Reducing Reactive Oxygen Species and Enhancing Mitochondrial Membrane Potential.

Phytic acid (PA) has been reported to possess anti-inflammatory and antioxidant properties that are critical for neuroprotection in neuronal disorders. This raises the question of whether PA can effectively protect sensory neurons against chemotherapy-induced peripheral neuropathy (CIPN). Peripheral neuropathy is a dose-limiting side effect of chemotherapy treatment often characterized by severe and abnormal pain in hands and feet resulting from peripheral nerve degeneration. Currently, there are no effective treatments available that can prevent or cure peripheral neuropathies other than symptomatic management. Herein, we aim to demonstrate the neuroprotective effects of PA against the neurodegeneration induced by the chemotherapeutics cisplatin (CDDP) and oxaliplatin. Further aims of this study are to provide the proposed mechanism of PA-mediated neuroprotection. The neuronal protection and survivability against CDDP were characterized by axon length measurements and cell body counting of the dorsal root ganglia (DRG) neurons. A cellular phenotype study was conducted microscopically. Intracellular reactive oxygen species (ROS) was estimated by fluorogenic probe dichlorofluorescein. Likewise, mitochondrial membrane potential (MMP) was assessed by fluorescent MitoTracker Orange CMTMRos. Similarly, the mitochondria-localized superoxide anion radical in response to CDDP with and without PA was evaluated. The culture of primary DRG neurons with CDDP reduced axon length and overall neuronal survival. However, cotreatment with PA demonstrated that axons were completely protected and showed increased stability up to the 45-day test duration, which is comparable to samples treated with PA alone and control. Notably, PA treatment scavenged the mitochondria-specific superoxide radicals and overall intracellular ROS that were largely induced by CDDP and simultaneously restored MMP. These results are credited to the underlying neuroprotection of PA in a platinum-treated condition. The results also exhibited that PA had a synergistic anticancer effect with CDDP in ovarian cancer in vitro models. For the first time, PA's potency against CDDP-induced PN is demonstrated systematically. The overall findings of this study suggest the application of PA in CIPN prevention and therapeutic purposes.

Electrical stimulation enhances mitochondrial trafficking as a neuroprotective mechanism against chemotherapy-induced peripheral neuropathy.

Electrical stimulation (ESTIM) has shown to be an effective symptomatic treatment to treat pain associated with peripheral nerve damage. However, the neuroprotective mechanism of ESTIM on peripheral neuropathies is still unknown. In this study, we identified that ESTIM has the ability to enhance mitochondrial trafficking as a neuroprotective mechanism against chemotherapy-induced peripheral neuropathies (CIPNs). CIPN is a debilitating and painful sequalae of anti-cancer chemotherapy treatment which results in degeneration of peripheral nerves. Mitochondrial dynamics were analyzed within axons in response to two different antineoplastic mechanisms by chemotherapy drug treatments paclitaxel and oxaliplatin in vitro. Mitochondrial trafficking response to chemotherapy drug treatment was observed to decrease in conjunction with degeneration of distal axons. Using low-frequency ESTIM, we observed enhanced mitochondrial trafficking to be a neuroprotective mechanism against CIPN. This study confirms ESTIM enhances regeneration of peripheral nerves by increased mitochondrial trafficking.

Mitochondrial trafficking as a protective mechanism against chemotherapy drug-induced peripheral neuropathy: Identifying the key site of action.

AIMS: Chemotherapy induced peripheral neuropathy (CIPN) is a common side effect seen in patients who have undergone most chemotherapy treatments to which there are currently no treatment methods. CIPN has been shown to cause axonal degeneration leading to Peripheral Neuropathy (PN), which can lead to major dosage reduction and may prevent further chemotherapy treatment due to oftentimes debilitating pain. Previously, we have determined the site-specific action of Paclitaxel (PTX), a microtubule targeting agent, as well as the neuroprotective effect of Fluocinolone Acetonide (FA) against Paclitaxel Induced Peripheral Neuropathy (PIPN). MAIN METHODS: Mitochondrial trafficking analysis was determined for all sample sets, wherein FA showed enhanced anterograde (axonal) mitochondrial trafficking leading to neuroprotective effects for all samples. KEY FINDINGS: Using this system, we demonstrate that PTX, Monomethyl auristatin E (MMAE), and Vincristine (VCR), are toxic at clinically prescribed levels when treated focally to axons. However, Cisplatin (CDDP) was determined to have a higher toxicity when treated to cell bodies. Although having different targeting mechanisms, the administration of FA was determined to have a significant neuroprotective effect for against all chemotherapy drugs tested. SIGNIFICANCE: This study identifies key insights regarding site of action and neuroprotective strategies to further development as potential therapeutics against CIPN. FA was treated alongside each chemotherapy drug to identify the neuroprotective effect against CIPN, where FA was found to be neuroprotective for all drugs tested. This study found that treatment with FA led to an enhancement in the anterograde movement of mitochondria based on fluorescent imaging.

A review on current brain organoid technologies from a biomedical engineering perspective.

Brain organoids are 3D cytoarchitectures resembling the embryonic human brain. This review focuses on current advancements in biomedical engineering methods to develop organoids such as pluripotent stem cells assemblies, quickly aggregated floating culture, hydrogel suspension, microfluidic systems (both photolithography and 3D printing), and brain organoids-on-a-chip. These methods have the potential to create a large impact on neurological disorder studies by creating a model of the human brain investigating pathogenesis and drug screening for individual patients. 3D brain organoid cultures mimic not only features of patients' unknown drug reactions, but also early human brain development at cellular, structural, and functional levels. The challenge of current brain organoids lies in the formation of distinct cortical neuron layers, gyrification, and the establishment of complex neuronal circuitry, as they are critically specialized, developmental aspects. Furthermore, recent advances such as vascularization and genome engineering are in development to overcome the barrier of neuronal complexity. Future technology of brain organoids is needed to improve tissue cross-communication, body axis simulation, cell patterning signals, and spatial-temporal control of differentiation, as engineering methods discussed in this review are rapidly evolving.

Fluocinolone Acetonide Enhances Anterograde Mitochondria Trafficking and Promotes Neuroprotection against Paclitaxel-Induced Peripheral Neuropathy.

Paclitaxel (PTX)-induced peripheral neuropathy (PIPN) is a debilitating health condition which is a result of degeneration of peripheral nerves found in extremities. Currently, there are no established treatment methods that can prevent or protect from PIPN. Fluocinolone acetonide (FA) has been recently identified as a potential candidate for protection from PIPN. However, the fundamental mechanism of action is still unknown. In this study, we showed that enhanced anterograde mitochondrial movement in dorsal root ganglion (DRG) cells has a major role in FA-mediated neuroprotection in PIPN. In this study, cells were treated with PTX or FA along with their combination followed by mitochondrial fluorescence staining. Somal (proximal) and axonal (distal) mitochondria were selectively stained using a microfluidic compartmentalized chamber with different MitoTrackers blue and red, respectively, which we termed, the two-color staining approach. Results revealed that axons were protected from degeneration by the PTX effect when treated along with FA. PTX exposure alone resulted in low mitochondrial mobility in DRG cells. However, cotreatment with PTX and FA showed significant enhancement of anterograde trafficking of somal (proximal) mitochondria to distal axons. Similarly, cotreatment with FA restored mitochondrial mobility significantly. Overall, this study affirms that increasing mitochondrial recruitment into the axon by cotreatment with FA can be a worthwhile strategy to protect or prevent PIPN. The proposed two-color staining approach can be extended to study trafficking for other neuron-specific subcellular organelles.

The Encapsulation of Bioactive Plant Extracts into the Cellulose Microfiber Isolated from G. optiva Species for Biomedical Applications.

Agricultural waste-based cellulose fibers have gained significant interest for a myriad of applications. Grewia optiva (G. optiva), a plant species, has been widely used for feeding animals, and the small branches' bark is used for making rope. Herein, we have extracted cellulose fibers from the bark of G. optiva species via chemical treatments (including an alkaline treatment and bleaching). The gravimetric analysis revealed that the bark of G. Optiva contains cellulose (63.13%), hemicellulose (13.52%), lignin (15.13%), and wax (2.8%). Cellulose microfibre (CMF) has been synthesized from raw fibre via chemical treatment methods. The obtained cellulose fibers were crosslinked and employed as the matrix to encapsulate the bioactive plant extracts derived from the root of Catharanthus roseus (C. roseus). The microscopic images, XRD, FTIR, and antibacterial/antioxidant activity confirmed the encapsulation of natural extracts in the cellulose microfiber. The microscopic images revealed that the encapsulation of the natural extracts slightly increased the fiber's diameter. The XRD pattern showed that the extracted cellulose microfiber had an average crystalline size of 2.53 nm with a crystalline index of 30.4% compared to the crystalline size of 2.49 nm with a crystalline index of 27.99% for the plant extract incorporated membrane. The water uptake efficiency of the synthesized membrane increased up to 250%. The antimicrobial activity of the composite (the CMF-E membrane) was studied via the zone inhibition against gram-positive and gram-negative bacteria, and the result indicated high antibacterial activity. This work highlighted G. optiva-derived cellulose microfiber as an optimum substrate for antimicrobial scaffolds. In addition, this paper first reports the antimicrobial/antioxidant behavior of the composite membrane of the C. roseus extract blended in the G. optiva microfiber. This work revealed the potential applications of CMF-E membranes for wound healing scaffolds.

A Review on the Technological Advances and Future Perspectives of Axon Guidance and Regeneration in Peripheral Nerve Repair.

Despite a significant advance in the pathophysiological understanding of peripheral nerve damage, the successful treatment of large nerve defects remains an unmet medical need. In this article, axon growth guidance for peripheral nerve regeneration was systematically reviewed and discussed mainly from the engineering perspective. In addition, the common approaches to surgery, bioengineering approaches to emerging technologies such as optogenetic stimulation and magnetic stimulation for functional recovery were discussed, along with their pros and cons. Additionally, clear future perspectives of axon guidance and nerve regeneration were addressed.

Polypyrrole Nanotunnels with Luminal and Abluminal Layered Double Hydroxide Nanosheets Grown on a Carbon Cloth for Energy Storage Applications.

The structural design of transition metal-based electrode materials with gigantic energy storage capabilities is a crucial task. In this work, we report an assembly of thin layered double hydroxide (LDH) nanosheets arrayed throughout the luminal and abluminal parts of polypyrrole tunnels fastened onto both sides of a carbon cloth as a battery-type energy storage system. Electron microscopy images reveal that the resulting electrode (NiCo-LDH@H-PPy@CC, where H-PPy@CC represents carbon cloth-supported hollow polypyrrole fibers) is constructed by combining luminal and abluminal NiCo-LDH nanosheets onto a long polypyrrole tunnel on a carbon cloth. The primary sample shows an excellent specific capacity of 149.16 mAh g-1 at 1.0 mA cm-2, a remarkable rate capability of 80.45%, and comprehensive cyclic stability (93.4%). The improved performance is mainly attributed to the strategic organization of the electrode materials with superior Brunauer-Emmett-Teller (BET) surface area and conductivity. Moreover, an asymmetric supercapacitor device assembled with NiCo-LDH@H-PPy@CC and vanadium phosphate-incorporated carbon nanofiber (VPO@CNFs900) electrodes contributes a specific energy density of 32.42 Wh kg-1 at 3 mA cm-2 with a specific power density of 359.16 W kg-1. When the current density is increased by 6-fold, the specific power density reaches 1999.89 W kg-1 at a specific energy density of 20.06 Wh kg-1. This is a simple, cost-effective, and convenient synthetic strategy for the synthesis of porous nanosheet arrays assimilated into hollow fiber architectures, which can illuminate the ideal approach for the fabrication of novel materials with an immense potential for energy storage.

Characteristics and outcomes of hospitalized adults with COVID-19 in Nepal: a multicenter, prospective cohort study.

INTRODUCTION: There is limited data on clinical course and outcomes of hospitalized adults with COVID-19 in Nepal. Thus, it is imperative to characterize the features of this disease in the domestic context. METHODOLOGY: We identified all adult patients with laboratory-confirmed COVID-19 admitted to five different hospitals in Nepal from June 15 to July 15, 2020. We collected epidemiological, socio-cultural and clinicopathologic data, and stratified the patients based on their symptom status. RESULTS: The study included 220 patients with an overall median age of 31.5 (25-37) years, and 181 (82.3%) were males. 159 (72.3%) were asymptomatic, and 163 (74.1%) were imported cases. Of 217 patients with the available data, 110 (50.7%) reported their annual household income less than 2000 US dollars, and 122 (56.2%) practiced Pranayama (yogic rhythmic breathing techniques) regularly. Eight patients (3.6%) required supplemental oxygen and two patients (0.9%) died. None of the patients who practiced Pranayama regularly required supplemental oxygen. Compared to asymptomatic patients, symptomatic patients had greater proportion of females (31.1% vs. 12.6%, p = 0.001), imported cases (85.2% vs. 69.8%, p = 0.02), illiterates (26.8% vs. 12.1%, p = 0.01), alcohol users (43.3% vs. 24.5%, p = 0.01), and had higher platelet count (253×109/L vs. 185×109/L, p = 0.02). CONCLUSIONS: Most cases were imported, asymptomatic young males, with very few deaths. Pranayama practice was associated with protection against severe COVID-19, but more data is needed to substantiate this. The association of platelets count with symptom status in the Nepalese population needs further exploration.

Integrating the Essence of a Metal-Organic Framework with Electrospinning: A New Approach for Making a Metal Nanoparticle Confined N-Doped Carbon Nanotubes/Porous Carbon Nanofibrous Membrane for Energy Storage and Conversion.

The fabrication of an economic and efficient multifunctional advanced nanomaterial with a rational composition and configuration by a facile methodology is a crucial challenge. Herein, we are the first to report the growth of Co nanoparticle-integrated nitrogen-doped carbon nanotubes (N-CNTs) on porous carbon nanofibers by simply heating in the situ-developed metal-organic framework (MOF)-based electrospun nanofibrous membrane with no need for an external supply of any additional precursors and reducing gases. The long and entangled N-CNTs originating from highly porous and graphitic carbon nanofibers offer good flexibility, large surface area, high porosity, high conductivity, the homogeneous incorporation of heteroatoms and metallic constituents, and an abundant exposure of active nanocatalytic sites. The as-developed nanoassembly demonstrates attractive characteristics for electrocatalytic hydrogen and oxygen evolution reactions and electrochemical energy storage. This strategy of integrating the essence of an MOF with electrospinning offers a new, direct, and cost-effective approach for making N-doped CNT-based multifunctional membranes.

Development of an Axon-Guiding Aligned Nanofiber-Integrated Compartmentalized Microfluidic Neuron Culture System.

Microfluidic-based neuron cell culture systems have recently gained a lot of attention due to their efficiency in supporting the spatial and temporal control of cellular microenvironments. However, the lack of axon guidance is the key limitation in current culture systems. To combat this, we have developed electrospun aligned nanofiber-integrated compartmentalized microfluidic neuron culture systems (NIMSs), where the nanofibers have enabled axonal guidance and stability. The resulting platform significantly improved axon alignment, length, and stability for both rat primary embryonic motor neurons (MNs) and dorsal root ganglia (DRG) neurons compared to the conventional glass-based microfluidic systems (GMSs). The results showed that axonal growth covered more than two times the area on the axonal chamber of NIMSs compared to the area covered for GMSs. Overall, this platform can be used as a valuable tool for fundamental neuroscience research, drug screening, and biomaterial testing.

Three dimensional polycaprolactone/cellulose scaffold containing calcium-based particles: a new platform for bone regeneration.

Conventional electrospun membranes are composed of nanofibers arranged packed together with limited porosity akin to a two-dimensional (2D) sheet in which the growth of cells is restricted on the surface. In this study, we report a three-dimensional (3D) hierarchical multilayer scaffold with additional functionality by the modified gas-foaming technique. Calcium hydroxide particles were in-situ deposited on the fiber surface throughout the layers of macroporous 3D scaffold by the sodium borohydride (NaBH4) reduction of calcium salt. Mechanical properties and biocompatibility of the conventional electrospun mat were enhanced by the underlying 3D multilayer structure and incorporation of calcium hydroxide particles. Besides, the expanded 3D nanofiber scaffold with calcium incorporation promoted cellular infiltration, mineralization and osteogenesis. This integrated 3D multilayer structure and additional functionality approach may advance the development of 2D electrospun based scaffolds for biomedical applications.

Integrated design and fabrication strategies for biomechanically and biologically functional PLA/ß-TCP nanofiber reinforced GelMA scaffold for tissue engineering applications.

We present an integrated design and fabrication strategy for the development of hierarchically structured biomechanically and biologically functional tissue scaffold. An integration of ß-TCP incorporated fluffy type nanofibers and biodegradable interpenetrating gelatin-hydrogel networks (IGN) result in biomimetic tissue engineered constructs with fully tunable properties that can match specific tissue requirements. FESEM images showed that nanofibers were efficiently assembled into an orientation of IGN without disturbing its pore architecture. The pore architecture, compressive stiffness and modulus, swelling, and the biological properties of the composite constructs can be tailored by adjusting the composition of nanofiber content with respect to IGN. Experimental results of cell proliferation assay and confocal microscopy imaging showed that the as-fabricated composite constructs exhibit excellent ability for MC3T3-E1 cell proliferation, infiltration and growth. Furthermore, ß-TCP incorporated functionalized nanofiber enhanced the biomimetic mineralization, cell infiltration and cell proliferation. Within two weeks of cell-seeding, the composite construct exhibited enhanced osteogenic performance (Runx2, osterix and ALP gene expression) compared to pristine IGN hydrogel scaffold. Our integrated design and fabrication approach enables the assembly of nanofiber within IGN architecture, laying the foundation for biomimetic scaffold.

Phytic acid controlled in situ synthesis of amorphous cobalt phosphate/carbon composite as anode materials with a high mass loading for symmetrical supercapacitor: amorphization of the electrode to boost the energy density.

Transition metal phosphate (TMPi)-based composites as anode electrode materials in supercapacitor applications are less reported. Herein, we report a phytic acid (PA)-assisted in situ-formed amorphous cobalt phosphate/carbon (CoPi/C) composite grown on a flexible woven carbon cloth (CC) via a simple one-step carbonization approach. The tunable synthesis of amorphous and crystalline composites is shown by simply controlling the concentration of the cobalt salts. The strategy for high mass loading to 12 mg cm-2 is also shown in this report. Importantly, the resulting amorphous electrode materials exhibit electric double-layer capacitance (EDLC) behavior that works over a wide potential range from -1.4 to +0.5 V in an aqueous solution of potassium hydroxide (2 M KOH) and from -1.5 to +1.5 V in sodium sulfate (1 M Na2SO4). The amorphous electrode as an anode is capable of delivering an areal capacitance up to 2.15 F cm-2 at a current density of 4 mA cm-2 (gravimetric capacitance up to 606.1 F g-1 at 1 Ag-1) and has a retention of 94.2% at 10 000 cycles. The flexible solid-state symmetric device fabricated shows an energy density of approximately 620.0 µW h cm-2 at a power density of 4.7 mW cm-2 (31.1 W h kg-1 at 476.0 W kg-1). This study offers a novel route for the generation of metal phosphate-based anode materials with high capacitance for symmetrical supercapacitor device with high energy density.

Three-dimensional porous carbonaceous network with in-situ entrapped metallic cobalt for supercapacitor application.

Herein, we outline the fabrication of highly porous three-dimensional carbon-fiber network anchored with uniform metallic cobalt (Co) via electrospinning and subsequent post-modification approaches. First, cobalt acetate solution saturated electrospun polyacrylonitrile (PAN) nanofibrous mat was subjected to sodium borohydride (NaBH4) solution which results in the fabrication of three dimensional (3D) hierarchical multilayer network. Restructuring of the 2D mat into multilayered sponges with metal particles entrapment is attributed to the in-situ generated hydrogen gas into the interconnected pores of the fibrous network simultaneous with reduction of cobalt salt into metallic cobalt by NaBH4. The resulting mesh was stabilized and carbonization at inert atmosphere to obtain metallic cobalt (Co) embedded 3D carbon nanofibrous networks (Co@3D-CNFs). Physicochemical characterization and electrochemical analysis were performed. Results show carbon network was found to be expanded with bubbling like structures often embedded metallic Co nanoparticles. X-ray diffraction (XRD) pattern confirms the existence of the metallic cobalt particles on the carbon fiber networks. Furthermore, we establish a resulting composite (Co@3D-CNFs) identify the enhanced electrochemical performance having specific capacitance 762 F g-1 compared to 173 and 180 F g-1 for corresponding @3D-CNFs and 2D carbon nanofiber network with cobalt doped (Co@2D-CNFs) counterparts, respectively. The assembled Co2@3D-CNFs//NGH ASC device exhibits a high energy density 24.6 W h Kg-1 at 797 W kg-1 power density with an operating voltage of 1.6 V (vs Ag/AgCl). The device further shows good capacitance retention (90.1%) after 5000 cycles. This research shows the simple and cost-effective strategy to make metallic particles embedded 3D porous carbonaceous electrode materials which can have great potential for energy storage application.

Thromboresistant semi-IPN hydrogel coating: Towards improvement of the hemocompatibility/biocompatibility of metallic stent implants.

Here we developed a semi-interpenetrating network (IPN) hydrogel obtained by free radical polymerization to fabricate a coated stent with the aim of incorporating a natural topography present in the human body to improve biological activity. The method involves sandwiching a bare metal stent in the semi-IPN hydrogel via solution cast molding. The bio-functionality of the membrane could be tuned by incorporating Polydopamine into the matrix, and also the mechanical property was optimized by choosing an adequate concentration of acrylamide. The coating containing polydopamine hydrogel showed good mechanical stability under continuous flow condition, as demonstrated by crimping and deployment into a catheter without damage. Stent polymer bonding was enhanced via polydopamine incorporation in the matrix. The non-thrombogenicity of the coating containing hydrogel was confirmed through dynamic hemocompatibility studies in vitro. Vascular simulations, including other biomechanical performance, like durability testing, radial strength, and recoil, were demonstrated. The dopamine containing hydrogel membrane (DCHM) was found to promote cell material interaction due to the ability of the catechol to bind protein and induce HUVECs cytoplasmic spreading, proliferation, and migration, with reduced smooth muscle cell (SMCs) activity. SMCs inhibition correlated well with the amount of incorporated catechol in the matrix. Our results show that this material used as coated stent could be more effective in suppressing platelet aggregation with improved haemocompatibility/biocompatibility for faster re-endothelialization than bare metal stent (BMS).

Polydopamine-based Implantable Multifunctional Nanocarpet for Highly Efficient Photothermal-chemo Therapy.

We report a design and fabricate multifunctional localized platform for cancer therapy. Multiple stimuli-responsive polydopamine (PDA) was used for surface modification of electrospun doxorubicin hydrochloride (DOX) loaded polycaprolactone (PCL) fibers to make a designated platform. Photothermal properties such as photothermal performance and stability of the resulting composite mats were studied under the irradiation of the near-infrared (NIR) laser of 808 nm. With the incorporation of PDA into the fiber, a remarkable increase of local temperature was recorded under NIR illumination in a concentration-dependent manner with excellent stability. Drug released assay results revealed PDA coated PCL-DOX mats showed pH and NIR dual responsive behavior thereby exhibiting improved drug release in an acidic medium compared to physiological pH condition (pH 7.4) which is further increased by NIR exposure. The cancer activity in vitro of the mats was evaluated using cell counting (CCK) and live and dead cell assays. The combined effect of NIR mediated hyperthermia and chemo release resulting improved cells death has been reported. In summary, this study presents a major step forward towards a therapeutic model to cancer treatment utilizing pH and NIR dual responsive property from PDA alone in a fibrous mat.

Sacrificial template-based synthetic approach of polypyrrole hollow fibers for photothermal therapy.

In the present work, polypyrrole hollow fibers (PPy-HFs) were fabricated by sacrificial removal of soft templates of electrospun polycaprolactone (PCL) fibers with polypyrrole (PPy) coating through chemical polymerization of pyrrole monomer. Different physicochemical properties of as-fabricated PPy-HFs were then studied by Field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), Fourier transform infra-red (FT-IR) spectroscopy, Differential scanning calorimetry/Thermogravimetric analysis (DSC/TGA), and X-ray photoelectron spectroscopy (XPS). The photothermal activity of PPy-HF was studied by irradiating 808-nm near infra-red (NIR) light under different power values with various concentrations of PPy-HFs dispersed in phosphate buffer solution (PBS, pH 7.4). These PPy-HFs exhibited enhanced photothermal performance compared with polypyrrole nanoparticles (PPy-NPs). Furthermore, these PPy-HFs showed photothermal effect that was laser-power- and concentration-dependent. The photothermal toxicity of the resulting nanofiber was evaluated using cell counting kit-8 (CCK-8) and live and dead cell assays. Results showed that these PPy-HFs were more effective in killing cancer cells under NIR irradiation. In contrast, hollow-fiber showed no cytotoxicity without NIR exposure. Among different nanofiber formulations, PPy-160 exhibited the highest photothermal toxicity. It could be explained by its enhanced photothermal performance compared to other specimens. The resulting PPy-HFs showed superior drug-loading capacity to PPy-NPs. This might be attributed to adequate binding of the drug into both luminal and abluminal hollow-fiber surfaces. Fabrication of this substrate type opens a promising new avenue for architectural design of biocompatible organic polymer for biomedical field.

Short duration cancer treatment: inspired by a fast bio-resorbable smart nano-fiber device containing NIR lethal polydopamine nanospheres for effective chemo-photothermal cancer therapy.

BACKGROUND: The objective of this study was to evaluate the efficacy of a combination of Photothermal therapy (PTT) and chemotherapy in a single nano-fiber platform containing lethal polydopamine nanopheres (PD NPs) for annihilation of CT 26 cancer cells. METHOD: Polydioxanone (PDO) nanofiber containing PD and bortezomib (BTZ) was fabricated via electrospinning method. The content of BTZ and PD after optimization was 7% and 2.5% respectively with respect to PDO weight. PD NPs have absorption band in near-infrared (NIR) with resultant rapid heating capable of inducing cancer cell death. The samples was divided into three groups - PDO, PDO+PD, and PDO+PD-BTZ for analysis. RESULTS: In combined treatment, PDO nanofiber alone could not inhibit cancer cell growth as it neither contain PD or BTZ. However, PDO+PD fiber showed a cell viability of approximately 20% after 72 hr of treatment indicating minimal killing via hyperthermia. In the case of PDO composite fiber containing BTZ, the effect of NIR irradiation reduced the viability of cancer cells down to around 5% after 72 h showing the efficiency of combination therapy on cancer cells elimination. However, due to higher photothermal conversion that may negatively affect normal cells above 46°C, we have employed 1 s "OFF" and 2 s "ON" after initial 9 s continuous irradiation to maintain the temperature between 42 and 46°C over 3 mins of treatment using 2 W/cm2; 808 nm laser which resulted to similar cell death. CONCLUSION: In this study, combination of PTT and chemotherapy treatment on CT 26 colon cancer cells within 3 min resulted in effective cell death in contrast to single treatment of either PTT and chemotherapy alone. Our results suggest that this nanofiber device with efficient heating and remote control drug delivery system can be useful and convenient in the future clinical application for localized cancer therapy.

Nano-Nets Covered Composite Nanofibers with Enhanced Biocompatibility and Mechanical Properties for Bone Tissue Engineering.

Enhancing the biocompatibility profiles including cell attachment, growth, and viability and mechanical properties of designed synthetic scaffolds have an essential role in tissue engineering applications. Polymer blending is one of the most effective methods for providing new anticipated biomaterials for tissue scaffolds. Here, the blend solution of the different mass weight ratio of polycaprolactone (PCL) to human serum albumin (HSA) was subjected to fabricate nanocomposite spider-web-like membranes using electrospinning process. The physicochemical aspects of fabricated membranes had been characterized by a different state of techniques like that of scanning electron microscopy (FE-SEM), Fourier transform infrared spectroscopy (FT-IR), thermal gravimetric analysis (TGA), contact angle meter and universal testing machine. FE-SEM images revealed that all PCL/HSA mats were composed of interlinked nano-nets along with conventional electrospun fibers while nano-nets were not found for pristine PCL mat. Moreover, composite membranes exhibited improved water absorbability, enhanced biodegradation compared to pristine PCL membrane and had much better mechanical properties (tensile strength increased by up to 3-fold, Young's modulus by 2-fold). The cell attachment and proliferation tests were carried by culturing Mc3T3-E1 (pre-osteoblasts) with the designated nanofibrous membranes. The hybrid nanofibers exhibited extraordinary support for the adhesion and proliferation of cells when compared to the pristine PCL membrane. These results indicate that the nano-nets supported PCL/HSA scaffolds can be promising for tissue engineering applications.