Pablo R. Cortez Tornello

Structural characterization of electrospun micro/nanofibrous scaffolds by liquid extrusion porosimetry: A comparison with other techniques

Poly(ε-caprolactone) micro/nanofibrous scaffolds obtained by electrospinning technique from polymer solutions were characterized in terms of fiber diameter (as measured by scanning electron microscopy-SEM), pore size and its distribution (as measured by liquid extrusion porosimetry), and porosity (as determined by gravimetric measurement, liquid intrusion method, SEM image analysis and liquid extrusion porosimetry - LEP). Nonwoven micro/nanofibrous scaffolds were formed by uniform bead-free fibers with mean diameters in the range of 0.4 to 7 μm. The results indicate that pore size and pore size distribution are strongly associated to fiber diameter. Porosity results were analyzed taking into account the accuracy and limitations of each method. LEP resulted as the most suitable technique for measuring through-pore diameter and porosity. In order to compare empirical data of pore size from LEP, a theoretical multiplanar model for stochastic fiber networks was applied. The results predicted by the model were in good agreement with the experimental data provided by LEP for mean diameters higher than 1 μm. The present study shows the potential of LEP as a valuable instrumental technique for characterizing the porous structure of electrospun fibrous scaffolds.

Didanosine-loaded poly(epsilon-caprolactone) microparticles by a coaxial electrohydrodynamic atomization (CEHDA) technique

The goal of this study was to investigate the electrohydrodynamic atomization (EHDA) technology to encapsulate the water-soluble antiretroviral didanosine (ddI) within poly(epsilon-caprolactone) (PCL) particles and stabilize it in the gastric medium where it undergoes fast degradation. A preliminary study employing a one-needle setup enabled the adjustment of the critical process parameters. Then, a configuration of two concentric needles named coaxial electrohydrodynamic atomization (CEHDA) led to the formation of ddI-loaded PCL microcapsules. Scanning electron microscopy analysis showed that the microparticles were spherical and with narrow size distribution. Attenuated total reflectance/Fourier transform infrared spectroscopy confirmed that most of the drug was efficiently encapsulated within the particles, whereas differential scanning calorimetry and X-ray powder diffraction revealed that the drug was preserved mainly in crystalline form. The loading capacity was relatively high (approximately 12% w/w), and the encapsulation efficiency was approximately 100%. In vitro release assays (PBS pH = 7.4) indicated that ddI was released almost completely within 2 h. Moreover, the delayed release was expected to isolate ddI from the biological fluids during the gastric transit. Finally, pharmacokinetics studies in rats showed that ddI-loaded particles lead to a statistically significant increase of the oral bioavailability of almost 4 times and a 2-fold prolongation of the half-life with respect to a ddI aqueous solution, supporting the use of CEHDA as a promising reproducible, scalable and cost-viable technology to encapsulate water-soluble drugs within polymeric particles.

Amphiphilic electrospun scaffolds of PLLA–PEO–PPO block copolymers: preparation, characterization and drug-release behaviour

Biocompatible amphiphilic copolymers are attractive candidates for the fabrication of electrospun scaffolds to be used for tissue engineering and the delivery of biologically active compounds. The amphiphilic block copolymers poly(L-lactide)-b-poly(ethylene oxide)-b-poly(L-lactide) (PELA) and poly(L-lactide)-b-poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide)-b-poly(L-lactide) (PEPELA), which contain amorphous/crystalline and hydrophilic/hydrophobic blocks, were synthesized by ring-opening polymerization, and then electrospun to obtain non-woven fibrous scaffolds. Acetaminophen (AC) and celecoxib (CL) were used as hydrophilic and hydrophobic model drugs, respectively, to prepare drug-loaded scaffolds. The pure and drug-loaded scaffolds present a morphology characterized by randomly oriented fibres with integrated beads. The drug encapsulation and release profiles were determined by ultraviolet-visible spectroscopy. Due to the amphiphilic nature of PELA and PEPELA, both hydrophilic and hydrophobic drugs could be entrapped within the polymeric scaffolds, allowing the design of drug-delivery systems for specific applications. The combination of confocal Raman spectroscopy mapping and dynamic mechanical analysis revealed that the AC drug is preferentially maintained in the PEO phase, while the CL drug is fractionated between polyether and polyester phases and distributed throughout the fibrous structure due to its hydrophobic character.

Multilayered electrospun nanofibrous scaffolds for tailored controlled release of embelin

ABSTRACT Polymeric electrospun meshes are highly attractive as versatile platforms for numerous biomedical applications, tissue engineering, biosensors, and controlled release of bioactive agents. Herein, we describe the preparation and characterization of multilayered nanofibrous poly(ε-caprolactone) scaffolds with different embelin content by electrospinning technique. In vitro release in physiological and acidic pH and kinetic analysis were performed. The results show that it is possible to modulate the release profile depending on the number and thickness of layers added to drug-loaded scaffold that acts as an embelin reservoir. Electrospun multilayered scaffolds present characteristics, morphology and release profiles that could be very attractive for use as embelin controlled release systems.

Micro/nanofiber-based scaffolds for soft tissue engineering applications: Potential and current challenges

Bioresorbable micro/nanofiber-based structures are being studied as promising candidates for tissue engineering applications. Among the existing techniques for producing these matrices, electrospinning has attracted interest in many technological fields as a versatile and powerful processing technique. Electrospun micro/nanofibers possess high surface-area-to-volume ratio, high porosity and pore interconnectivity, and tunable fiber morphology and orientation. Moreover, submicron fibers are found in the extracellular matrix of natural organs and tissues. To date, many synthetic and natural polymers, biodegradable or non-biodegradable polymers, ceramics and composite materials, have been successfully electrospun using a plethora of techniques. Although in the beginning electrospinning was focused in producing two-dimensional structures, nowadays three-dimensional structures are also being developed. Besides the progress in the electrospinning process achieved in recent years, there still remain a number of challenges, such as mechanical, physical, and chemical biomimeticity, pore size enlargement, surface functionalization, therapeutic agent/cell loading, vascularization, and cell infiltration. This chapter reviews the research advances made in electrospun scaffolds for soft tissue engineering applications focusing on wound dressing, cartilage, muscle, cardiovascular, nerve, and skin tissues.

Nanofibras electrohiladas para usos terapéuticos.

Res_eng:Nanofibrous materials have a huge potential for the development of both extracellular matrices for tissue engineering applications and new systems for therapeutic agents delivery. In this chapter, the fundamentals for preparation of polymeric or composite nanofibrous matrices by electrospinning of solutions are briefly presented. Although electrospinning is a versatile technique for nanofiber production, the process is very complex and it depends on numerous processing parameters and intrinsic properties of the solution. The main variables that affect the process, the commercially available equipment and recent developments are described. In the biomedical field, several strategies for cell incorporation, techniques for pore enlargement and cellular infiltration improvement as well as cell behavior in nanofibrous structures, are presented. Among the main applications in the biomedical field, the ongoing research advances in tissue engineering (bone, cartilage, vascular, nerve and skin) and the development of multifunctional matrices for controlled release of therapeutic agents are discussed. Future perspectives on development and new applications of nanofibrous biomaterials are finally mentioned.