Biomedical subjects

Meital Zilberman

Publications and source records attributed to Meital Zilberman.

10 recordsLinked to original sources

PubMed2007

A mathematical model for predicting controlled release of bioactive agents from composite fiber structures.

A mathematical model for predicting bioactive agent release profiles from core/shell fiber structures was developed and studied. These new composite fibers, which combine good mechanical properties with desired protein release profiles, are designed for use in tissue regeneration and other biomedical applications. These fibers are composed of an inner dense polymeric core surrounded by a porous bioresorbable shell, which encapsulates the bioactive agent molecules. The model is based on Fick's second law of diffusion, and on two major assumptions: (a) first-order degradation kinetics of the porous shell, and (b) a nonconstant diffusion coefficient for the bioactive agent, which increases with time because of degradation of the host polymer. Three factors are evaluated and included in this model: a porosity factor, a tortuosity factor, and a polymer concentration factor. Our study indicates that the model correlates well with in vitro release results, exhibiting a mean error of less than 2.2% for most studied cases. In this study, the model was used for predicting protein release profiles from fibers with shells of various initial molecular weights and for predicting the release of proteins with various molecular weights. This new model exhibits a potential for simulating fibrous systems for a wide variety of biomedical applications.

Biocompatible Materials↗

PubMed2007

Biomedical coatings based on chitin soluble extract for inhibition of fungal adhesion to polymeric surfaces.

Indwelling medical devices made of polymeric materials, such as intravenous (IV) catheters, are known risk factors for development of fungal infection, particularly systemic candidiasis, that are a significant cause of morbidity and lethality in compromised patients. Candida can form a biofilm on the polymeric surface, serving as a nidus for systemic, difficult to eradicate infection. The current research focuses on development and study of a chitin soluble extract (CSE) coating on polyurethane (PU), in order to reduce the level of adherence of C. albicans to the PU surface. The immobilization of CSE onto the PU surface was performed using both, chemical binding and physical adsorption. Our results indicate that CSE develops a unique tertiary structure in which basic elements in the range of 100 nm build "fingers" and these "fingers" are arranged in a concentric structure around a center. The CSE coated films showed 75% inhibition of C. albicans adhesion for the chemical binding and 83% for the physical adsorption coating and even after 11 weeks the inhibitory effect on adhesion is still significant. Hence, our new coatings may lead to a new generation of medical devices with surfaces that can prevent fungal adhesion.

Candida↗

PubMed2007

Paclitaxel-loaded composite fibers: microstructure and emulsion stability.

New core/shell fiber structures loaded with paclitaxel were developed and studied. These composite fibers are ideal for forming thin, delicate, biomedically important structures for various applications. Possible applications include fiber-based endovascular stents that mechanically support blood vessels while delivering drugs for preventing restenosis directly to the blood vessel wall, or drug delivery systems for cancer treatment. The core/shell fiber structures were formed by "coating" nylon fibers with porous paclitaxel-containing poly(DL-lactic-co-glycolic acid) structures. Shell preparation ("coating") was performed by freeze-drying water in oil emulsions. The present study focused on the effects of the emulsion's formulation (composition) and processing conditions on the porous shell structure, which actually reflects the emulsion's stability and also the drug release profile from the fibers. In general, extremely porous "shell" structures were obtained with good adhesion to the core fiber. An increase in the emulsion's drug content and copolymer composition demonstrated a significant effect on pore size and distribution, because of enhanced emulsion instability, whereas the homogenization rate and duration had only a slight effect on the pores' microstructure. The thermodynamic parameters in the studied system are thus more important than the kinetic parameters in determining the emulsion's stability and the shell's porous structure.

Biocompatible Materials↗

PubMed2006

Novel bioresorbabale composite fiber structures loaded with proteins for tissue regeneration applications: microstructure and protein release.

Novel bioresorbable core/shell composite fiber structures loaded with proteins were developed and studied. These unique polymeric structures are designed to combine good mechanical properties with a desired controlled protein-release profile, to serve as scaffolds for tissue regeneration applications. Core/shell fiber structures were formed by "coating" poly(L-lactic acid) fibers with protein-containing poly(DL-lactic-co-glycolic acid) porous structures. Shell preparation (coating) was performed by the freeze-drying of water in oil emulsions. The present study focused on the effect of the emulsion's formulation on the porous shell structure and on the resulting cumulative protein release from the composite fibers for 90 days. Horseradish peroxidase (HRP) was used as the protein source. The release profiles usually exhibited an initial burst effect, accompanied by a decrease in release rate with time, as is typical for diffusion-controlled systems. The HRP content and the emulsion's organic:aqueous phase ratio exhibited significant effects on both the shell microstructure and the HRP release profile from the composite fibers, whereas the polymer content of the emulsion's organic phase only affected these fiber characteristics in certain cases. Proper selection of the emulsion's parameters can yield core/shell fiber structures with the desired protein release behavior and other useful physical properties.

Biocompatible Materials↗

PubMed2006

Novel composite fiber structures to provide drug/protein delivery for medical implants and tissue regeneration.

A novel class of bioresorbable composite (core/shell) fiber structures loaded with bioactive agents was developed and studied. These unique polymeric structures are designed to combine good mechanical properties with a desired controlled release profile, in order to serve as scaffolds for tissue regeneration applications and as basic elements of medical implants. These core/shell fiber structures were formed by "coating" core polymer fibers with drug/protein-containing poly(dl-lactic-co-glycolic acid) porous structures. The shell preparation ("coating") was performed by the freeze-drying of water-in-oil emulsions. Both water soluble and water insoluble agents can be incorporated in these structures and their activity is preserved, since the fiber fabrication requires neither high temperatures nor harsh solvents in the vicinity of the bioactive agents. Examples for release profiles of protein (horseradish peroxidase) and drug (paclitaxel) are presented. We have demonstrated that appropriate selection of the emulsion's parameters can yield a variety of new core/shell fiber structures with desirable drug/protein release behavior. This will lead to the engineering of new implants and scaffolds, and will advance the field of tissue regeneration and medical implants.

Drug Delivery Systems↗

PubMed2006

Microsphere-based bioresorbable structures loaded with proteins for tissue regeneration applications.

Novel bioresorbable fiber/microsphere composite structures loaded with proteins were developed and studied. These unique polymeric structures are designed to combine good mechanical properties with a desired controlled protein-release profile, in order to serve as scaffolds for tissue regeneration applications. The composite fiber structures were formed by "coating" poly(L-lactic acid) fibers with protein-containing poly(DL-lactic-co-glycolic acid) microspheres. The microspheres were prepared by a double emulsion technique and were loaded with the model enzyme horseradish peroxidase (HRP). The present study focused on the effect of the double emulsion's composition and processing conditions on the microsphere structure and on the resulting cumulative protein release for 90 days. The release profiles generally exhibited an initial burst effect, a lag period and an increased release rate after 2 months. HRP release from these structures was governed by diffusion, rather than by degradation. A decrease in the emulsion's mixing rate significantly improved the release profile through unique matrix-like structures. The initial burst effect can be reduced by decreasing the internal phase quantity and its protein content, or by adding a surfactant to the internal emulsion. Proper selection of the double emulsion formulation and processing conditions can yield fiber microsphere structures with the desired protein release behavior.

Biocompatible Materials↗

PubMed2006

Drug-eluting bioresorbable stents for various applications.

A stent is a medical device designed to serve as a temporary or permanent internal scaffold to maintain or increase the lumen of a body conduit. Metallic coronary stents were first introduced to prevent arterial dissections and to eliminate vessel recoil and intimal hyperplasia associated with percutaneous transluminal coronary angioplasty. The stent application range has expanded as more experience was gained, and encouraging results have been obtained in the treatment of vascular diseases. Stents are currently used for support of additional body conduits, including the urethra, trachea, and esophagus. The rationale for bioresorbable stents is the support of a body conduit only during its healing process. The stent mass and strength decrease with time, and the mechanical load is gradually transferred to the surrounding tissue. Bioresorbable stents also enable longer term delivery of drugs to the conduit wall from an internal reservoir and abolish the need for a second surgery to remove the device. The present review describes recent advances in bioresorbable stents, focusing on drug-eluting bioresorbable stents for various applications. Controlled release of an active agent from a stent can be used to enhance healing of the surrounding tissues, to increase the implant's biocompatibility, as well as to help cure certain diseases. Because a lot of research in this field has been done by us, examples for these functions are described based mainly on developments in our laboratories.

Absorbable Implants↗

PubMed2005

Mechanical properties and in vitro degradation of bioresorbable fibers and expandable fiber-based stents.

Bioresorbable polymeric support devices (stents) are being developed in order to improve the biocompatibility and drug reservoir capacity of metal stents, as well as to offer a temporary alternative to permanent metallic stents. These temporary devices may be utilized for coronary, urethral, tracheal, and other applications. The present study focuses on the mechanical properties of bioresorbable fibers as well as stents developed from these fibers. Fibers made of poly(L-lactide) (PLLA), polydioxanone (PDS), and poly(glycolide-co-epsilon-caprolactone) (PGACL) were studied in vitro. These fibers combine a relatively high initial strength and modulus together with sufficient ductility and flexibility, and were therefore chosen for use in stents. The effect of degradation on the tensile mechanical properties and morphology of these fibers was examined. The expandable stents developed from these fibers demonstrated excellent initial radial compression strength. The PLLA stents exhibited excellent in vitro degradation resistance and can therefore support body conduits such as blood vessels for prolonged periods of time. PDS and PGACL stents can afford good support for 5 and 2 weeks, respectively, and can therefore be utilized for short-term applications. The degradation resistance of the stents correlates with the profile of mechanical property deterioration of the corresponding bioresorbable fibers.

Absorbable Implants↗

PubMed2004

Protein-loaded bioresorbable fibers and expandable stents: Mechanical properties and protein release.

There is an increasing interest in bioresorbable polymeric stents for coronary, urethral and tracheal applications. These stents can support body conduits during their healing process and release biologically active agents from an internal reservoir to the surrounding tissue. A removal operation is not needed. Bioresorbable poly(L-lactic acid) fibers were prepared through melt spinning accompanied by a postpreparation drawing process. Novel expandable bioresorbable stents were developed from these fibers. Bioresorbable microspheres containing albumin were prepared and attached to the stents, to serve as a protein reservoir coating. The controlled release of albumin from the microsphere-loaded stent was studied. The fibers combine high strength and modulus, together with good ductility and flexibility. An increase in draw ratio increases the tensile strength and modulus and decreases the ultimate strain. The stents demonstrated excellent initial radial compression strength and good in vitro degradation resistivity, which makes them applicable for supporting blood vessels for at least 20 weeks. Microspheres bound to these stents enable effective protein loading, without reducing the stent's mechanical properties. The protein release from the microsphere-loaded stent occurs by diffusion, is determined mainly by the initial molecular weight of the bioresorbable polymer and its erosion rate, and is strongly affected by the microsphere structure.

Animals↗

PubMed2003

Bioresorbable polymeric stents: current status and future promise.

Metal stents and, more recently, polymer-coated metal stents are used to stabilize dissections, eliminate vessel recoil, and guide remodeling after balloon angioplasty and other treatments for arterial disease. Bioresorbable polymeric stents are being developed to improve the biocompatibility and the drug reservoir capacity of metal stents, and to offer a transient alternative to the permanent metallic stent implant. Following a brief review of metal stent technology, the emerging class of expandable, bioresorbable polymeric stents is described, with emphasis on developments in the authors' laboratory.

Biodegradation, Environmental↗