pH-responsive drug release from functionalized electrospun poly(caprolactone) scaffolds under simulated in vivo environment.

The difference in the tumor environment from the normal healthy tissue can be therapeutically exploited to develop new strategies for controlled and site-specific drug delivery. In the present study, a continuous flow system is designed to represent the in vivo environment of a tumor tissue and drug release is studied at different pH that represents normal tissue pH, tumor tissue pH, and stomach pH. The results obtained from these experiments were translated to a human embryonic kidney cell culture system and the effect of drug released from these functionalized PCL scaffolds on cell viability was studied. A significant decrease in cell viability was observed with the doxorubicin hydrochloride concentration that would be released at acidic pH, either present as a result of tumor extracellular environment or could be achieved via fabrication of a composite scaffold with a polyvinyl alcohol hydrogel containing acid. In the end, a study using zebrafish as an animal model is also undertaken in order to study the drug release from the scaffolds in vivo.

Functionalization of electrospun poly(caprolactone) fibers for pH-controlled delivery of doxorubicin hydrochloride.

Functionalized electrospun polymer fibers are a promising candidate for controlled delivery of chemotherapeutic drugs to improve the therapeutic efficacy and to reduce the potential toxic effects by delivering the drug at a rate governed by the physiological need of the site of action. In this study, poly(caprolactone) (PCL) fibers were fabricated by electrospinning, followed by hydrolyzation to introduce functional groups on the fiber surface. Characterization studies were performed on these functionalized fibers using X-ray photoelectron spectroscopy, scanning electron microscopy, and Toluidine Blue O dye assay. The pH-sensitivity of the functional groups on the fiber surface and doxorubicin hydrochloride was utilized to bind the drug electrostatically to these functionalized PCL fibers. The effect of pH on drug loading and release kinetics was investigated. Results indicate successful electrostatic binding of the drug to functionalized electrospun fibers and a high drug payload. The drug delivery response can be modulated by introduction of suitable stimuli (pH).

Hydrolyzed Poly(acrylonitrile) Electrospun Ion-Exchange Fibers.

A potential ion-exchange material was developed from poly(acrylonitrile) fibers that were prepared by electrospinning followed by alkaline hydrolysis (to convert the nitrile group to the carboxylate functional group). Characterization studies performed on this material using X-ray photoelectron spectroscopy, scanning electron microscopy, Fourier-Transform infra-red spectroscopy, and ion chromatography confirmed the presence of ion-exchange functional group (carboxylate). Optimum hydrolysis conditions resulted in an ion-exchange capacity of 2.39 meq/g. Ion-exchange fibers were used in a packed-bed column to selectively remove heavy-metal cation from the background of a benign, competing cation at a much higher concentration. The material can be efficiently regenerated and used for multiple cycles of exhaustion and regeneration.

Fibronectin adsorption on functionalized electrospun polycaprolactone scaffolds: experimental and molecular dynamics studies.

Designing scaffolds to modulate protein adsorption is a key to building advanced scaffolds for tissue regeneration. Protein adsorption to tissue engineering scaffolds is critical in early cell attachment, survival, and eventual proliferation. The goal of this study is to examine the effect of functionalization on fibronectin adsorption to electrospun polycaprolactone (PCL) scaffolds through experimentation using fluorescently labeled fibronectin and to couple this experimental data with analysis of interaction energies obtained through molecular dynamics (MD) simulations to develop a better understanding of the adsorption process. This study is the first to analyze and compare experimental and MD simulation results of fibronectin adsorption on functionalized electrospun PCL scaffolds. Electrospun nanofiber PCL scaffolds were treated with either 1 N NaOH (hydrolyzed) or 46% hexamethylenediamine (HMD) (aminated) solution to be compared with untreated (control) scaffolds. We found that aminated PCL scaffolds experimentally adsorbed more fibronectin than control scaffolds, whereas hydrolyzed scaffolds showed decreased adsorption. MD simulations carried out with NVT ensemble at a temperature of 310 K indicated a higher work of adhesion for both functionalized scaffolds over control. Also, the simulations revealed different conformations of fibronectin on each scaffold type after adsorption, with the arginine-glycine-aspartic acid sequence appearing most accessible on the aminated scaffolds. This suggests that functionalization affects not only the quantity of protein that will adsorb on a scaffold but how it attaches as well, which could affect subsequent cell attachment.

Altering surface characteristics of polypropylene mesh via sodium hydroxide treatment.

Incisional hernias represent a serious and common complication following laparotomy. The use of synthetic (e.g. polypropylene) meshes to aid repair of these hernias has considerably reduced recurrence rates. While polypropylene is biocompatible and has a long successful clinical history in treating hernias and preventing reherniation, this material may suffer some limitations, particularly in challenging patients at risk of wound failure due to, for example, an exaggerated inflammation reaction, delayed wound healing, and infection. Surface modification of the polypropylene mesh without sacrificing its mechanical properties, critical for hernia repair, represents one way to begin to address these clinical complications. Our hypothesis is treatment of a proprietary polypropylene mesh with sodium hydroxide (NaOH) will increase in vitro NIH/3T3 cell attachment, predictive of earlier and improved cell colonization and tissue integration of polypropylene materials. Our goal is to achieve this altered surface functionality via enhanced removal of chemicals/oils used during material synthesis without compromising the mechanical properties of the mesh. We found that NaOH treatment does not appear to compromise the mechanical strength of the material, despite roughly a 10% decrease in fiber diameter. The treatment increases in vitro NIH/3T3 cell attachment within the first 72 h and this effect is sustained up to 7 days in vitro. This research demonstrates that sodium hydroxide treatment is an efficient way to modify the surface of polypropylene hernia meshes without losing the mechanical integrity of the material. This simple procedure could also allow the attachment of a variety of biomolecules to the polypropylene mesh that may aid in reducing the complications associated with polypropylene meshes today.