Ludwig Erik Aguilar

A Controlled Design of Aligned and Random Nanofibers for 3D Bi-functionalized Nerve Conduits Fabricated via a Novel Electrospinning Set-up

Scaffolds made of aligned nanofibers are favorable for nerve regeneration due to their superior nerve cell attachment and proliferation. However, it is challenging not only to produce a neat mat or a conduit form with aligned nanofibers but also to use these for surgical applications as a nerve guide conduit due to their insufficient mechanical strength. Furthermore, no studies have been reported on the fabrication of aligned nanofibers and randomly-oriented nanofibers on the same mat. In this study, we have successfully produced a mat with both aligned and randomly-oriented nanofibers by using a novel electrospinning set up. A new conduit with a highly-aligned electrospun mat is produced with this modified electrospinning method, and this proposed conduit with favorable features, such as selective permeability, hydrophilicity and nerve growth directional steering, were fabricated as nerve guide conduits (NGCs). The inner surface of the nerve conduit is covered with highly aligned electrospun nanofibers and is able to enhance the proliferation of neural cells. The central part of the tube is double-coated with randomly-oriented nanofibers over the aligned nanofibers, strengthening the weak mechanical strength of the aligned nanofibers.

pH/NIR Light-Controlled Multidrug Release via a Mussel-Inspired Nanocomposite Hydrogel for Chemo-Photothermal Cancer Therapy

This study reports on an intelligent composite hydrogel with both pH-dependent drug release in a cancer environment and heat generation based on NIR laser exposure, for the combined application of photothermal therapy (PTT) and multidrug chemotherapy. For the first time in the literature, Dopamine nanoparticle (DP) was incorporated as a highly effective photothermal agent as well as anticancer drug, bortezomib (BTZ) carrier inside a stimuli responsive pNIPAAm-co-pAAm hydrogel. When light is applied to the composite hydrogel, DP nanoparticle absorbs the light, which is dissipated locally as heat to impact cancer cells via hyperthermia. On the other hand, facile release of the anticancer drug BTZ from the surface of DP encapsulated hydrogel could be achieved due to the dissociation between catechol groups of DP and the boronic acid functionality of BTZ in typical acidic cancer environment. In order to increase the synergistic effect by dual drug delivery, Doxorubicin (DOXO) were also loaded to pNIPAAm-co-pAAm/DP-BTZ hydrogel and the effect of monotherapy as well as combined therapy were detailed by a complete characterization. Our results suggest that these mussel inspired nanocomposite with excellent heating property and controllable multidrug release can be considered as a potential material for cancer therapy.

On-demand drug release and hyperthermia therapy applications of thermoresponsive poly-(NIPAAm-co-HMAAm)/polyurethane core-shell nanofiber mat on non-vascular nitinol stents

A functional cover made up of core-shell nanofibers with a unique combination of thermoresponsive polymeric shell and stretchable polymeric core for non-vascular nitinol stents that uses an alternating magnetic field (AMF) to induce heat in the stent for hyperthermia therapy and simultaneously release 5-fluorouracil and/or paclitaxel was designed. Varying the ratios of NIPAAm to HMAAm monomer resulted in different LCST properties for the synthesized copolymer and further utilized for an on-demand drug release. Biocompatibility test using NIH-3T3 fibroblast cells indicates that the composite with drug content is biocompatible and the in-vitro cancer cytotoxicity test using ESO26 and OE21 cancer cells proved that the material shows cancer cytotoxic properties via combination of dual drug and hyperthermia therapy. With this functional material, we propose a tailorable and on-demand drug release with more control that can be employed for a combination drug therapy/single drug therapy combined with hyperthermia therapy for cancer cytotoxicity effect.

Electrospun polyurethane/Eudragit ® L100-55 composite mats for the pH dependent release of paclitaxel on duodenal stent cover application.

A nanofiber composite mat of PU and Eudragit(®) L100-55 was created using electrospinning process. The pH dependent release of paclitaxel was successfully done with the use of PU/EL100-55 nanocomposite mats as the controlling platform. The morphology of the nanofiber composites was surveyed using FESEM and ratios of the polymers affects the diameter of the nanofiber. Characterization of the nanofiber composite mat was done using FTIR, DSC-TGA method. The release rate of paclitaxel was determined and analyzed by in vitro drug release method. In order to mimic the condition of a human duodenum, the fibers were submersed on PBS of different pH levels (4.0, 6.0,) respectively, and then analyzed using high performance liquid chromatography (HPLC). Composite mats submersed in PBS with pH 4.0 showed lesser release profile compared to mats submersed in PBS with pH of 6.0. The composite mat has adequate mechanical properties and in vitro cell biocompatibility indicating that the material can be used for drug eluting stent cover application.

Computational Analysis of the Design and Experimental Application of the Migration and Durability Testing Device for Oesophageal Stent

An oesophageal stent durability/migration testing device was developed based on the mathematical analysis of durability mechanism of an oesophageal stent and oesophageal motility, in which the oesophageal stent was assumed to be under simulated in vivo pre compression load, in vivo creep load and internal environment. Hardware and software simulating an oesophageal tube movement was developed, which consists of six sensors, an Arduino MEGA and LabVIEW LIFO interface. Accurate detection of stent migration in an oesophageal model using camera imageprocessing analysis and Flexi force Pressure Sensor (FPS) combine was done. The control board for the real time monitoring of non-vascular oesophageal stents used Arduino MEGA2560. LabVIEW was used to monitor in real time the FPS and bend sensor,camera image processing on the stent durability/migration testing device. The testing results can verify the design of stent’s fatigue life and to ensure the records for the optimization of oesophagus stent design, this can ensure the trustworthiness of oesophagus stent implantation in vivo. This device could further evaluate the effectivity for all type of stents on non-vascular applications and also to test experimental materials on stents. Also, the said device can be modified and applied to test the migration and fatigue life of other GI stents.

Functionalized Non-vascular Nitinol Stent via Electropolymerized Polydopamine Thin Film Coating Loaded with Bortezomib Adjunct to Hyperthermia Therapy

Gastrointestinal malignancies have been a tremendous problem in the medical field and cover a wide variety of parts of the system, (i.e. esophagus, duodenum, intestines, and rectum). Usually, these malignancies are treated with palliation with the use of non-vascular nitinol stents. However, stenting is not a perfect solution for these problems. While it can enhance the quality of life of the patient, in time the device will encounter problems such as re-occlusion due to the rapid growth of the tumor. In this study, we propose a functionalization technique using electropolymerization of polydopamine directly onto the nitinol stent struts for the combined application of hyperthermia and chemotherapy. The coating was characterized using FESEM, XPS, and FT-IR. Drug release studies show that facile release of the anticancer drug BTZ from the surface of the polydopamine-coated stent could be achieved by the dissociation between catechol groups of polydopamine and the boronic acid functionality of BTZ in a pH-dependent manner. The anti-cancer property was also evaluated, and cytotoxicity on ESO26 and SNU-5 cancer cell lines were observed. Our results suggest that the introduced approach can be considered as a potential method for therapeutic stent application.

Investigation of Composite Nano Air Filter for Improving Antimicrobial Activity and Reducing VOCs Using a High Speed Upward Electrospinning System

A new nano air filter for fine dust filtration with antibacterial and volatile organic compounds (VOCs) adsorption properties was fabricated using a bottom-up, high-speed electrospinning system. To optimize production, polyurethane fibers were electrospun at various voltages on polypropylene nonwoven fabrics, and results show that fiber diameter decreased as voltage increased. Silver nanoparticles (AgNPs) and Activated Carbon (AC) were used as antimicrobials and VOC-reducing agents. FTIR, SEM, and EDS were performed to analyze the resulting filter fabricated by electrospinning. FTIR and EDS results show that the AgNPs and activated carbon added to the PU fibers were successfully integrated into the PP nonwoven fabric.

Publisher Correction: Functionalized Non-vascular Nitinol Stent via Electropolymerized Polydopamine Thin Film Coating Loaded with Bortezomib Adjunct to Hyperthermia Therapy

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

A Review on Properties of Natural and Synthetic Based Electrospun Fibrous Materials for Bone Tissue Engineering

Bone tissue engineering is an interdisciplinary field where the principles of engineering are applied on bone-related biochemical reactions. Scaffolds, cells, growth factors, and their interrelation in microenvironment are the major concerns in bone tissue engineering. Among many alternatives, electrospinning is a promising and versatile technique that is used to fabricate polymer fibrous scaffolds for bone tissue engineering applications. Copolymerization and polymer blending is a promising strategic way in purpose of getting synergistic and additive effect achieved from either polymer. In this review, we summarize the basic chemistry of bone, principle of electrospinning, and polymers that are used in bone tissue engineering. Particular attention will be given on biomechanical properties and biological activities of these electrospun fibers. This review will cover the fundamental basis of cell adhesion, differentiation, and proliferation of the electrospun fibers in bone tissue scaffolds. In the last section, we offer the current development and future perspectives on the use of electrospun mats in bone tissue engineering.

Implantable chemothermal brachytherapy seeds: A synergistic approach to brachytherapy using polymeric dual drug delivery and hyperthermia for malignant solid tumor ablation

Graphical abstract Figure. No caption available. &NA; Chemothermal brachytherapy seeds have been developed using a combination of polymeric dual drug chemotherapy and alternating magnetic field induced hyperthermia. The synergistic effect of chemotherapy and hyperthermia brachytherapy has been investigated in a way that has never been performed before, with an in‐depth analysis of the cancer cell inhibition property of the new system. A comprehensive in vivo study on athymic mice model with SCC7 tumor has been conducted to determine optimal arrays and specifications of the chemothermal seeds. Dual drug chemotherapy has been achieved via surface deposition of polydopamine that carries bortezomib, and also via loading an acidic pH soluble hydrogel that contains 5‐Fluorouracil inside the chemothermal seed; this increases the drug loading capacity of the chemothermal seed, and creates dual drug synergism. An external alternating magnetic field has been utilized to induce hyperthermia conditions, using the inherent ferromagnetic property of the nitinol alloy used as the seed casing. The materials used in this study were fully characterized using FESEM, H1 NMR, FT‐IR, and XPS to validate their properties. This new approach to experimental cancer treatment is a pilot study that exhibits the potential of thermal brachytherapy and chemotherapy as a combined treatment modality.