Coaxial and Triaxial Structured Fibers by Electrospinning for Tissue Engineering and Sustained Drug Release

Coaxial and triaxial electrospinning are novel methods for fabrication of multilayered nano and micro-size fibers with desirable features such as co-solution blending, reinforced core, porous and hollow structure. However, the effect of type of fluids, solvent volatilities, polymer molecular weight, and co-solution blending properties (hydrophobicity/hydrophilicity) in multi-layered fibers have not been studied. In this work, coaxial electrospinning process was explored to determine the effect of type of core and solution rheology on jet stability and fibers formation using cellulose acetate (CA) as the shell material. Results from coaxial electrospinning of CA suggested that the fibers could be formed when the viscosity of the core is less than that of the sheath. Gelatin, chitosan, and mineral oil could be used as core fluids in the formation of core-shell and hollow CA fiber. Next, the coaxial process was scaled up to triaxial electrospinning to evaluate the effect of solvent volatility, type of polymer, polymer molecular weight, polymer solubility and polymer-solvent interactions at the interface and the mechanism of encapsulating the core fluid in multiaxial electrospinning. In triaxial electrospinning successful fiber formation was dependent on ensuring that the outer shell formed first, i.e., the relative solvent volatility of encapsulating core polymer to be lower than that of the shell polymer solvent. Based on the fundamental understanding of the formation of multiaxial fibers, I explored the use of these systems in a drug delivery application using biocompatible polymers of PCL blended gelatin (GT). In particular, I investigated the influence of hydrophobicity, hydrophilicity, drug-loading location, fiber size and co-solution blending properties in regulating the drug release in multi-layered fibers using Doxycycline (Dox) as a hydrophilic drug model. Drug release at 37?C over 5 days was controlled in coaxial GT-core and PCL/GT-core fibers while PCL-core had the least performance. The presence of additional layers decreased the burst release and tenability of drug release based on the selection of appropriate core-polymer. Thus, the unique fabrication process can be used to tailor the mechanical properties, biological properties and release of various factors, which can be potentially useful in a number of applications.Chemical Engineerin

In vivo investigation of the tissue response to commercial Teflon insulin infusion sets in large swine for 14 days: the effect of angle of insertion on tissue histology and insulin spread within the subcutaneous tissue.

Objective: This study investigated the effects of the inflammatory tissue response (ITR) to an insulin infusion set (IIS) on insulin bolus spread over wear time, as well as the effect of cannula insertion angle on the ITR, bolus shape, and pump tubing pressure. Research design and methods: Angled or straight IISs were inserted every other day for 14 days into the subcutaneous tissue of 11 swine and insulin was delivered continuously. Prior to euthanasia, a 70 µL bolus of insulin/X-ray contrast agent was infused while recording a pressure profile (peak tubing pressure, pmax; area under the pressure curve, AUC), followed by the excision of the tissue-catheter specimen. Bolus surface area (SA) and volume (V) were assessed via micro-CT. Tissue was stained to analyze total area of inflammation (TAI) and inflammatory layer thickness (ILT) surrounding the cannula. Results: A bolus delivered through an angled IIS had a larger mean SA than a bolus delivered through a straight cannula (314.0±84.2 mm2 vs 229.0±99.7 mm2, p\u3c0.001) and a larger volume (198.7±66.9 mm3 vs 145.0±65.9 mm3, p=0.001). Both decreased significantly over wear time, independent of angle. There was a significant difference in TAI (angled, 9.1±4.0 mm2 vs straight, 14.3±8.6 mm2, p\u3c0.001) and ILT (angled, 0.7±0.4 vs straight, 1.2±0.7 mm, p\u3c0.001). pmax (p=0.005) and AUC (p=0.014) were lower using angled IIS. As ILT increased, pmax increased, while SA and V decreased. Conclusions: The progression of the ITR directly affected bolus shape and tubing pressure. Although straight insertion is clinically preferred, our data suggest that an angled IIS elicits lower grades of ITR and delivers a bolus with lower tubing pressure and greater SA and V. The subcutaneous environment plays a crucial role in IIS longevity, and the insertion angle needs to be considered in future IIS designs and clinical trials

Production of hollow fibers by co-electrospinning of cellulose acetate

Thesis (MScEng (Process Engineering))--University of Stellenbosch, 2009.The study concerns the use of the electrospinning technique for the formation of cellulose acetate hollow nanofibers. These hollow fibers are used to manufacture hollow fiber membranes. Important properties that should be inherent to these hollow-nanofibers include excellent permeability and separation characteristics, and long useful life. They have potential applications in filtration, reverse osmosis, and the separation of liquids and gases. It is apparent from the available literature on electrospinning and co-electrospinning that the diameter and the morphology of the resulting fibers are significantly influenced by variations in the system and process parameters, which include the solution concentration, solvent volatility, solution viscosity, surface tension and the conductivity of the spinning solution. The materials used include cellulose acetate (CA) (concentration = 11~14 wt %), (feed rate = 1~3 ml/h), acetone:dioxane (2:1) and mineral oil (feed rate = 0.5~1 ml/h) with core and shell linear velocity of 2 and 0.7 mm/min respectively. These materials were used as received without further purification. The co-electrospinning setup used comprised a compound spinneret, consisting of two concentric small-diameter capillary tubes/needles, one located inside another (core-shell/co-axial design). The internal and external diameters of the inside and outside needles were 0.3 and 1.2 mm respectively (0.3 mm shell/core gap space). The liquids CA (shell) and mineral oil (core) are pumped to the coaxial needle by a syringe pump, forming a compound droplet at the tip of the needle. A high voltage source is used to apply a potential of several kilovolts over the electrospinning distance. One electrode is placed into the spinning solution and the other oppositely charged (or neutral) electrode attached to a conductive collector. If the charge build up reaches approximately 15 kV the charged compound droplet, (poorly conductive polymer solution) deforms into a conical structure called a Taylor cone. On further increasing, the charge at the Taylor cone to some critical value (unique to each polymer system) the surface tension of the compound Taylor cone is broken and a core-shell jet of polymer solution ejects from the apex of the Taylor cone. This jet is linear over a small distance, and then deviates in a course of violent whipping from bending instabilities brought about by repulsive charges existing along the jet length. The core-shell jet is stretched and solvent is evaporated and expelled, resulting in the thinning and alignment of the fiber. Ultimately dry (most solvent having been removed) submicron fibers are collected in alignment form in a simple collector design (water bath). The shell to core solution flow rate ratio was chosen according to the parameter response of shell-core diameter of the resulting fibers in order to achieve an optimal hollow structure after removal of the mineral oil core. The mineral oil of the dry collected core-shell fibers is removed by immersion in octane. The aforementioned response is determined by measurement of core-shell diameters using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The obtained results showed that the ability of the spinning solution to be electrospun was directly dependent on its concentration and the feed rate of the spinning solution and also parameters such as the spinning distance and type of solvents used. The preferable polymer solution concentration is 14 wt %, shell feed rate of 3 ml/hr, core feed rate of 0.5 ml/hr (2 and 0.7 mm/s core and shell linear velocity respectively), applied voltage of 15 KV, spinning distance of 8 cm and coaxial spinnerets having internal diameters of 0.3 mm and 1.2 mm core and shell needles respectively (0.3 mm shell/core gap space) have been found to make uniform cellulose acetate hollow fibers with an average inside and outside diameter of approximately 495 and 1266 nm, respectively