The mechanical behavior and biocompatibility of polymer blends for Patent Ductus Arteriosus (PDA) occlusion device.

Patent Ductus Arteriosus (PDA) is a cardiovascular defect that occurs in 1 out of every 2000 births, and if left untreated, may lead to severe cardiovascular problems. Current options for occluding utilize meta scaffolds with polymer fabric, and are permanent. The purpose of this study was to develop a fully degradable occluder for the closure of PDA, that can be deployed percutaneously without open-heart surgery. For percutaneous deployment, both elasticity and sufficient mechanical strength are required of the device components. As this combination of properties is not achievable with currently-available homo- or copolymers, blends of biodegradable poly(ε-caprolactone) (PCL) and poly(L-lactide-co-ε-caprolactone) (PLC) with various compositions were studied as the potential material for the PDA occlusion device. Microstructures of this blend were characterized by differential scanning calorimetry (DSC) and tensile tests. DSC results demonstrated the immiscibility between PCL and its copolymer PLC. Furthermore, the mechanical properties, i.e. elastic modulus and strain recovery, of the blends could be largely tailored by changing the continuous phase component. Based on the thermo-mechanical tests, suitable blends were selected to fabricate a prototype of PDA occluder and its in vitro performance, in term of device recovery (from its sheathed configuration), biodegradation rate and blood compatibility, was evaluated. The current results indicate that the device is able to recover elastically from a sheath within 2-3min for deployment; the device starts to disintegrate within 5-6 months, and the materials have no adverse effects on the platelet and leucocyte components of the blood. Biocompatibility implantation studies of the device showed acceptable tissue response. Finally, an artificial PDA conduit was created in a pig model, and the device deployment was tested from a sheath: the device recovered within 2-3min of unsheathing and fully sealed the conduit, the device remains stable and is completely covered by tissue at 1 month follow up. Thus, a novel prototype for PDA occlusion that is fully degradable has been developed to overcome the limitations of the currently used metal/fabric devices.

In vitro and in vivo performance of a dual drug-eluting stent (DDES).

This study reports on a dual drug-eluting stent (DDES) that has an anti-proliferative and an anti-thrombotic in a biodegradable polymer-coated onto a cobalt-chromium stent. The DDES was prepared by spray coating the bare metal stent with a biodegradable polymer loaded with sirolimus and triflusal, to treat against restenosis and thrombosis, respectively. The 2-layered dual-drug coated stent was characterized in vitro for surface properties before and after expansion, as well as for possible delamination by cross-sectioning the stent in vitro. The in vitro anti-platelet behavior of the triflusal-loaded films was investigated by using dynamic platelet adhesion measurements. Additionally, the in vitro degradation and release study of the films and the stents w/single sirolimus and dual sirolimus-triflusal in different formulations were examined. Finally, in vivo studies (in a porcine carotid artery model) were performed for acute thrombosis, inflammation and restenosis at 30 days. The in vitro results show DDES can sustain release both anti-proliferation drug (sirolimus) and anti-thrombosis drug (triflusal), two drugs were controlled in different rates to effectively reduce thrombosis and proliferation at the same time. In vivo results show a significant reduction in restenosis with dual-drug eluting stent compared with the controls (a bare metal stent, a sirolimus coated and a pure polymer-coated stent). The reduction in restenosis with a dual sirolimus-triflusal eluting stent is associated with an inhibition of inflammation, especially thrombus formation, suggesting that such dual-drug eluting stents have a role to play for the treatment of coronary artery disease.