Implantable medical devices can provide life-giving help to many systems in the body. Multifunctional devices provide several different services at the same time. When made of a bioresorbable polymer, such devices degrade with time by hydrolytic cleavage. The end products, carbon dioxide and water, are nontoxic. These devices can remain intact in the body for a predicted period of time - from weeks to years - and then degrade without the need for surgical removal. Their mechanical properties also change with time, due to degradation of the polymer, and this too can often be used to advantage.
Dr. Meital Zilberman, a new faculty member in TAU's Faculty of Engineering, has been developing multifunctional bioresorbable polymer stents. Stents are structural devices used, for example, to help keep veins and arteries open after angioplasty. Such devices can simultaneously deliver drugs, proteins or gene therapy agents to the surrounding tissue. The controlled release of such active agents can help increase the implant's biocompatibility, enhance healing of the surrounding tissues, and help cure certain diseases.
Processing techniques and parameters can have major effects on the microstructure, and thus the physical and mechanical properties of the polymer films and fibers that comprise these devices. Understanding the underlying process-structure-property relationships could thus lead to better systems. Proper selection of processing conditions, based on kinetic and thermodynamic considerations, can yield polymer/drug systems with desired drug-release behavior and other useful properties. Better control over the diffusion of the active components and the degradation of the host polymer can improve the delivery of drugs to surrounding tissues. Such processes are being studied using micro-structural analysis and mathematical modeling.
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| The design concept of endovascular stems: (a) pre-dilated, (b) dilated, (c) pre-dilated, side view, (d) dilated, side view. |
For example, percutaneous transluminal coronary angioplasty (which mechanically pushes open fatty blockages) is often used as an alternative to coronary artery bypass surgery. Metal stents are often inserted to keep the blood vessels open for a long period of time. A biodegradable endovascular stent would, however, offer several important advantages. During vessel healing, the stent would gradually transfer the mechanical load to the vascular wall, as stent degraded and lost mass and strength over time. Such stents could also provide long-term drug delivery to the vessel wall from an internal reservoir. Finally, there would be no need for surgery to remove the device.
Dr. Zilberman and her U.S. colleagues have developed a new, expandable and bioresorbable, polymer fiber-based stent (see figure), which demonstrates good mechanical properties and biocompatibility. In addition to its support function, the stent also locally administers pharmacological agents which could, for example, help prevent restenosis (reblockage). The stent is designed to remain intact in situ for 6-12 months before degrading to non-toxic substances, increasing the effective release of drug molecules from the device to the blood vessel wall.
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| Polymeric film structures showing drug dispersion in a semi-crystalline film (lower photo) and on its surface (middle photo). Upper photo - neat polymer film. | Polymeric film structures showing drug dispersion in a amorphous film (lower photo) and on its surface (middle photo). Upper photo - neat polymer film. |
Dr. Zilberman's novel tracheal stent is designed to support the collapsed airway in newborns and infants with congenital tracheomalacia. Such infants can have recurrent respiratory infections and apneic episodes, which can potentially lead to cardiac arrest. The metal stents currently used in blood vessels can also be used for airway support; however, a bioresorbable tracheal stent would provide support until the airway matures and then be totally resorbed, obviating the need for a removal operation. The new expandable stent prepared from a bioresorbable polymeric film, demonstrates good mechanical properties in vitro. Preliminary in vivo studies also demonstrate excellent proof of principle and tolerable biocompatibility.
Steroidal anti-inflammatory drugs, incorporated into the film, are locally released during the mechanical support phase. In addition to their anti-inflammatory activity, these steroids can also inhibit fibrotic responses and should, therefore, be helpful in preventing proliferative reactions, such as airway stenosis. The kinetics of the polymer/drug film-formation process strongly affects both drug location/dispersion in the film (see photomicrographs) and the drug release profile in the body. Research continues on this unique approach to lifesaving biodegradable devices.
