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      • Short duration cancer treatment: inspired by a fast bio-resorbable smart nano-fiber device containing NIR lethal polydopamine nanospheres for effective chemo–photothermal cancer therapy

        Obiweluozor, Francis O,Emechebe, Gladys A,Tiwari, Arjun Prasad,Kim, Ju Yeon,Park, Chan Hee,Kim, Cheol Sang Dove Medical Press 2018 International journal of nanomedicine Vol.13 No.-

        <P><B>Background</B></P><P>The objective of this study was to evaluate the efficacy of a combination of Photothermal therapy (PTT) and chemotherapy in a single nano-fiber platform containing lethal polydopamine nanopheres (PD NPs) for annihilation of CT 26 cancer cells.</P><P><B>Method</B></P><P>Polydioxanone (PDO) nanofiber containing PD and bortezomib (BTZ) was fabricated via electrospinning method. The content of BTZ and PD after optimization was 7% and 2.5% respectively with respect to PDO weight. PD NPs have absorption band in near-infrared (NIR) with resultant rapid heating capable of inducing cancer cell death. The samples was divided into three groups – PDO, PDO+PD, and PDO+PD-BTZ for analysis.</P><P><B>Results</B></P><P>In combined treatment, PDO nanofiber alone could not inhibit cancer cell growth as it neither contain PD or BTZ. However, PDO+PD fiber showed a cell viability of approximately 20% after 72 hr of treatment indicating minimal killing via hyperthermia. In the case of PDO composite fiber containing BTZ, the effect of NIR irradiation reduced the viability of cancer cells down to around 5% after 72 h showing the efficiency of combination therapy on cancer cells elimination. However, due to higher photothermal conversion that may negatively affect normal cells above 46°C, we have employed 1 s “OFF” and 2 s “ON” after initial 9 s continuous irradiation to maintain the temperature between 42 and 46°C over 3 mins of treatment using 2 W/cm<SUP>2</SUP>; 808 nm laser which resulted to similar cell death.</P><P><B>Conclusion</B></P><P>In this study, combination of PTT and chemotherapy treatment on CT 26 colon cancer cells within 3 min resulted in effective cell death in contrast to single treatment of either PTT and chemotherapy alone. Our results suggest that this nanofiber device with efficient heating and remote control drug delivery system can be useful and convenient in the future clinical application for localized cancer therapy.</P>

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        A Comparative Study of an Anti-Thrombotic Small-Diameter Vascular Graft with Commercially Available e-PTFE Graft in a Porcine Carotid Model

        이교선,KAYUMOV MUKHAMMAD,Emechebe Gladys A.,김도완,조화진,정윤진,이동원,박준규,박찬희,김철상,Obiweluozor Francis O.,정인석 한국조직공학과 재생의학회 2022 조직공학과 재생의학 Vol.19 No.3

        BACKGROUND: We have designed a reinforced drug-loaded vascular graft composed of polycaprolactone (PCL) and polydioxanone (PDO) via a combination of electrospinning/3D printing approaches. To evaluate its potential for clinical application, we compared the in vivo blood compatibility and performance of PCL/PDO ? 10%DY grafts doped with an antithrombotic drug (dipyridamole) with a commercial expanded polytetrafluoroethylene (e-PTFE) graft in a porcine model. METHODS: A total of 10 pigs (weight: 25–35 kg) were used in this study. We made a new 5-mm graft with PCL/PDO composite nanofiber via the electrospinning technique. We simultaneously implanted a commercially available e-PTFE graft (n = 5) and our PCL/PDO ? 10%DY graft (n = 5) into the carotid arteries of the pigs. No anticoagulant/antiplatelet agent was administered during the follow-up period, and ultrasonography was performed weekly to confirm the patency of the two grafts in vivo. Four weeks later, we explanted and compared the performance of the two grafts by histological analysis and scanning electron microscopy (SEM). RESULTS: No complications, such as sweating on the graft or significant bleeding from the needle hole site, were seen in the PCL/PDO ? 10%DY graft immediately after implantation. Serial ultrasonographic examination and immunohistochemical analysis demonstrated that PCL/PDO ? 10%DY grafts showed normal physiological blood flow and minimal lumen reduction, and pulsed synchronously with the native artery at 4 weeks after implantation. However, all e-PTFE grafts occluded within the study period. The luminal surface of the PCL/PDO ? 10%DY graft in the transitional zone was fully covered with endothelial cells as observed by SEM. CONCLUSION: The PCL/PDO ? 10%DY graft was well tolerated, and no adverse tissue reaction was observed in porcine carotid models during the short-term follow-up. Colonization of the graft by host endothelial and smooth muscle cells coupled with substantial extracellular matrix production marked the regenerative capability. Thus, this material may be an ideal substitute for vascular reconstruction and bypass surgeries. Long-term observations will be necessary to determine the anti-thrombotic and remodeling potential of this device.

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        Mussel-inspired elastic interpenetrated network hydrogel as an alternative for anti-thrombotic stent coating membrane

        Obiweluozor, Francis O.,Maharjan, Bikendra,Gladys Emechebe, A.,Park, Chan Hee,Kim, Cheol Sang Elsevier 2018 CHEMICAL ENGINEERING JOURNAL -LAUSANNE- Vol.347 No.-

        <P><B>Abstract</B></P> <P>Coated stents are classified as new generation stents wrapped with a thin polymeric membrane for the treatment of numerous vascular irregularities ranging from aneurysms to vascular leaks. Compared to partially covered and bare metal stents (BMS), fully covered stents promote less tissue granulation and suppress thrombosis, and can be designed to be post-operative retrievable. Fabrication method and material selection play significant roles in coated stent application, due to commercially available coated stents induce some degree restenosis. We have successfully fabricated a non-thrombotic and biocompatible fully coated stent made of a semi-interpenetrating network (IPN) hydrogel composed of acrylic acid (AA), dopamine methacrylamide (DMA), and methyl methacrylate (MMA) terpolymer (P(AA-co-MMA-co-DMA)/PU, incorporated with polyurethane (PU). We utilize a conventional mold casting method to fabricate a uniform covered stent, with the stent struts fully embedded within the hydrogel membrane. Firm polymer-stent bonding was achieved by introducing DMA into the matrix. We characterized the membrane by conducting platelet adhesion/activation studies followed by hemolysis and inflammatory potential evaluation which supports a non-thrombogenicity of the P(AA-co-MMA-co-DMA)/PU semi-IPN hydrogel membrane. The quality of the coated hydrogel membrane was evaluated by scanning electron microscopy (SEM); mechanical stability of the layer was analyzed by peeling test; tensile test, and multiple physical deformations tests. Further evaluation will be carried out in the near future to evaluate the potential <I>in vivo</I> application of this new semi-IPN hydrogel coated stent to remedy non-vascular leaks and other strictures.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Stent coating containing polydopamine to increase adhesion property was proposed. </LI> <LI> Incorporating PU as a second network greatly improve the mechanical property. </LI> <LI> The fabricated membrane create a stable coating that enable delivery with catheter. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

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