Cross-Linked, Biodegradable, Cytocompatible Salicylic Acid Based Polyesters for Localized, Sustained Delivery of Salicylic Acid: An In Vitro Study

In order to suppress chronic inflammation while supporting cell proliferation, there has been a continuous surge toward development of polymers with the intention of delivering anti-inflammatory molecules in a sustained manner. In the above backdrop, we report the synthesis of a novel, stable, cross-linked polyester with salicylic acid (SA) incorporated in the polymeric backbone and propose a simple synthesis route by melt condensation. The as-synthesized polymer was hydrophobic with a glass transition temperature of 1 degrees C, which increases to 17 degrees C upon curing. The combination of NMR and FT-IR spectral techniques established the ester linkages in the as-synthesized SA-based polyester. The pH-dependent degradation rate and the rate of release of salicylic acid from the as-synthesized SA-based polymer were studied at physiological conditions in vitro. The polyester underwent surface erosion and exhibited linear degradation kinetics in which a change in degradation rate is observed after 4-10 days and 24% mass loss was recorded after 4 months at 37 degrees C and pH 7.4. The delivery of salicylic acid also showed a similar change in slopes, with a sustained release rate of 3.5% in 4 months. The cytocompatibility studies of these polyesters were carried out with C2C12 murine myoblast cells using techniques like MTT assay and flow cytometry. Our results strongly suggest that SA-based polyester supports cell proliferation for 3 days in culture and do not cause cell death (<7%), as quantified by propidium iodide (PI) stained cells. Hence, these polyesters can be used as implant materials for localized, sustained delivery of salicylic acid and have applications in adjuvant cancer therapy, chronic wound healing, and as an alternative to commercially available polymers like poly(lactic acid) and poly(glycolic acid) or their copolymers.

Long-Term Sustained Release of Salicylic Acid from Cross-Linked Biodegradable Polyester Induces a Reduced Foreign Body Response in Mice

There has been a continuous surge toward developing new biopolymers that exhibit better in vivo biocompatibility properties in terms of demonstrating a reduced foreign body response (FBR). One approach to mitigate the undesired FBR is to develop an implant capable of releasing anti-inflammatory molecules in a sustained manner over a long time period. Implants causing inflammation are also more susceptible to infection. In this article, the in vivo biocompatibility of a novel, biodegradable salicylic acid releasing polyester (SAP) has been investigated by subcutaneous implantation in a mouse model. The tissue response to SAP was compared with that of a widely used biodegradable polymer, poly(lactic acid-co-glycolic acid) (PLGA), as a control over three time points: 2, 4, and 16 weeks postimplantation. A long-term in vitro study illustrates a continuous, linear (zero order) release of salicylic acid with a cumulative mass percent release rate of 7.34 x 10(-4) h(-1) over similar to 1.5-17 months. On the basis of physicochemical analysis, surface erosion for SAP and bulk erosion for PLGA have been confirmed as their dominant degradation modes in vivo. On the basis of the histomorphometrical analysis of inflammatory cell densities and collagen distribution as well as quantification of proinflammatory cytokine levels (TNF-alpha and IL-1 beta), a reduced foreign body response toward SAP with respect to that generated by PLGA has been unambiguously established. The favorable in vivo tissue response to SAP, as manifest from the uniform and well-vascularized encapsulation around the implant, is consistent with the decrease in inflammatory cell density and increase in angiogenesis with time. The above observations, together with the demonstration of long-term and sustained release of salicylic acid, establish the potential use of SAP for applications in improved matrices for tissue engineering and chronic wound healing.

Effect of solvent; enhancing the wettability and engineering the porous structure of a calcium phosphate/agarose composite for drug delivery

Tissue engineering deals with the regeneration of tissues for bone repair, wound healing, drug delivery, etc., and a highly porous 3D artificial scaffold is required to accommodate the cells and direct their growth. We prepared 3D porous calcium phosphate ((hydroxyapatite/beta-tricalcium phosphate)/agarose, (HAp/beta-TCP)/agarose) composite scaffolds by sol-gel technique with water (WBS) and ethanol (EBS) as solvents. The crystalline phases of HAp and beta-TCP in the scaffolds were confirmed by X-ray diffraction (XRD) analysis. The EBS had reduced crystallinity and crystallite size compared to WBS. WBS and EBS revealed interconnected pores of 1 mu m and 100 nm, respectively. The swelling ratio was higher for EBS in water and phosphate buffered saline (PBS). An in vitro drug loading/release experiment was carried out on the scaffolds using gentamicin sulphate (GS) and amoxicillin (AMX). We observed initial burst release followed by sustained release from WBS and EBS. In addition, GS showed more extended release than AMX from both the scaffolds. GS and AMX loaded scaffolds showed greater efficacy against Pseudomonas than Bacillus species. WBS exhibited enhanced mechanical properties, wettability, drug loading and haemocompatibility compared to EBS. In vitro cell studies showed that over the scaffolds, MC3T3 cells attached and proliferated and there was a significant increase in live MC3T3 cells. Both scaffolds supported MC3T3 proliferation and mineralization in the absence of osteogenic differentiation supplements in media which proves the scaffolds are osteoconducive. Microporous scaffolds (WBS) could assist the bone in-growth, whereas the presence of nanopores (EBS) could enhance the degradation process. Hence, WBS and EBS could be used as scaffolds for tissue engineering and drug delivery. This is a cost effective technique to produce scaffolds of degradable 3D ceramic-polymer composites.

Biofunctionalized surface-modified silver nanoparticles for gene delivery

Silver nanoparticles (AgNPs) find use in different biomedical applications including wound healing and cancer. We propose that the efficacy of the nanoparticles can be further augmented by using these particles for gene delivery applications. The objective of this work was to engineer biofunctionalized stable AgNPs with good DNA binding ability for efficient transfection and minimal toxicity. Herein, we report on the one-pot facile green synthesis of polyethylene glycol (PEG) stabilized chitosan-g-polyacrylamide modified AgNPs. The size of the PEG stabilized AgNPs was 38 +/- 4 nm with a tighter size distribution compared to the unstabilized nanoparticles which showed bimodal distribution of particle sizes of 68 +/- 5 nm and 7 +/- 4 nm. To enhance the efficiency of gene transfection, the Arg-Gly-Asp-Ser (RGDS) peptide was immobilized on the silver nanoparticles. The transfection efficiency of AgNPs increased significantly after immobilization of the RGDS peptide reaching up to 42 +/- 4% and 30 +/- 3% in HeLa and A549 cells, respectively, and significantly higher than 34 +/- 3% and 23 +/- 2%, respectively, with the use of polyethyleneimine (25 kDa). These nanoparticles were found to induce minimal cellular toxicity. Differences in cellular uptake mechanisms with RGDS immobilization resulting in improved efficiency are elucidated. This study presents biofunctionalized AgNPs for potential use as efficient nonviral carriers for gene delivery with minimal cytotoxicity toward augmenting the therapeutic efficacy of AgNPs used in different biomedical products.

Photobiomodulation by Low Power Laser Irradiation Involves Activation of Latent TGF-β1

Laser mediated stimulation of biological process was amongst its very first effects documented by Mester et al. but the ambiguous and tissue-cell context specific biological effects of laser radiation is now termed ‘Photobiomodulation’. We found many parallels between the reported biological effects of lasers and a multiface-ted growth factor, Transforming Growth Factor-β (TGF-β). This review outlines the interestingparallelsbetween the twofieldsand our rationalefor pursuingtheir potential causal correlation. We explored this correlation using an in vitro assay systems and a human clinical trial on healing wound extraction sockets that we reported in a recent publication. In conclusion we report that low power laser irradiation can activate latent TGF-β1 and β3 complexes and suggest that this might be one of the major modes of the photobiomodulatory effects of low power lasers.

Modeling and Field Oriented Control of Salient Pole Wound Field Synchronous Machine in Stator Flux Coordinates

This paper describes the field oriented control of a salient pole wound field synchronous machine in stator flux coordinates. The procedure for derivation of flux linkage equations along any general rotating axes including stator flux axes is given. The stator flux equations are used to identify the cross-coupling occurring between the axes due to saliency in the machine. The coupling terms are canceled as feedforward terms in the generation of references for current controllers to achieve good decoupling during transients. The design of current controller for stator-flux-oriented control is presented. This paper proposes the method of extending rotor flux closed loop observer for sensorless control of wound field synchronous machine. This paper also proposes a new sensorless control by using stator flux closed loop observer and estimation of torque angle using stator current components in stator flux coordinates. Detailed experimental results from a sensorless 15.8 hp salient pole wound field synchronous machine drive are presented to demonstrate the performance of the proposed control strategy from a low speed of 0.8 Hz to 50 Hz.

Starting scheme for load commutated inverter-fed wound field synchronous machine using an auxiliary low-power voltage source inverter

Conventional thyristor-based load commutated inverter (LCI)-fed wound field synchronous machine operates only above a minimum speed that is necessary to develop enough back emf to ensure commutation. The drive is started and brought up to a speed of around 10-15% by a complex `dc link current pulsing' technique. During this process, the drive have problems such as pulsating torque, insufficient average starting torque, longer starting time, etc. In this regard a simple starting and low-speed operation scheme, by employing an auxiliary low-power voltage source inverter (VSI) between the LCI and the machine terminals, is presented in this study. The drive is started and brought up to a low speed of around 15% using the VSI alone with field oriented control. The complete control is then smoothly and dynamically transferred to the conventional LCI control. After the control transfer, the VSI is turned off and physically disconnected from the main circuit. The advantages of this scheme are smooth starting, complete control of torque and flux at starting and low speeds, less starting time, stable operation, etc. The voltage rating of the required VSI is very low of the order of 10-15%, whereas the current rating is dependent on the starting torque requirement of the load. The experimental results from a 15.8 hp LCI-fed wound field synchronous machine are given to demonstrate the scheme.

Variable-speed wind power generation using doubly fed wound rotor induction machine - A comparison with alternative schemes

In this paper, a wind energy conversion system (WECS) using grid-connected wound rotor induction machine controlled from the rotor side is compared with both fixed speed and variable speed systems using cage rotor induction machine. The comparison is done on the basis of (I) major hardware components required, (II) operating region, and (III) energy output due to a defined wind function using the characteristics of a practical wind turbine. Although a fixed speed system is more simple and reliable, it severely limits the energy output of a wind turbine. In case of variable speed systems, comparison shows that using a wound rotor induction machine of similar rating can significantly enhance energy capture. This comes about due to the ability to operate with rated torque even at supersynchronous speeds; power is then generated out of the rotor as well as the stator. Moreover, with rotor side control, the voltage rating of the power devices and dc bus capacitor bank is reduced. The size of the line side inductor also decreasesd. Results are presented to show the substantial advantages of the doubly fed system.

Hybrid LCI/VSI Power Circuit-A Universal High-Power Converter Solution for Wound Field Synchronous Motor Drives

Load commutated inverter (LCI)-fed wound field synchronous motor drives are used for medium-voltage high-power drive applications. This drive suffers from drawbacks such as complex starting procedure, sixth harmonic torque pulsations, quasi square wave motor current, notches in the terminal voltages, etc. In this paper, a hybrid converter circuit, consisting of an LCI and a voltage source inverter (VSI), is proposed, which can be a universal high-power converter solution for wound field synchronous motor drives. The proposed circuit, with the addition of a current-controlled VSI, overcomes nearly all of the shortcomings present in the conventional LCI-based system besides providing many additional advantages. In the proposed drive, the motor voltage and current are always sinusoidal even with the LCI switching at the fundamental frequency. The performance of the drive is demonstrated with detailed experimental waveforms from a 15.8-hp salient pole wound field synchronous machine. Finally, a brief description of the control scheme used for the proposed circuit is given.

Variational Asymptotic Analysis of a Self-healing SMA Composite

A Shape Memory Alloy (SMA) wire reinforced composite shell structure is analyzed for self-healing characteristic using Variational Asymptotic Method (VAM). SMA behavior is modeled using a onedimensional constitutive model. A pre-notched specimen is loaded longitudinally to simulate crack propagation. The loading process is accompanied by martensitic phase transformation in pre-strained SMA wires, bridging the crack. To heal the composite, uniform heating is required to initiate reverse transformation in the wires and bringing the crack faces back into contact. The pre-strain in the SMA wires used for reinforcement, causes a closure force across the crack during reverse transformation of the wires under heating. The simulation can be useful in design of self-healing composite structures using SMA. Effect of various parameters, like composite and SMA material properties and the geometry of the specimen, on the cracking and self-healing can also be studied.