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>

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>

Thromboresistant semi-IPN hydrogel coating: Towards improvement of the hemocompatibility/biocompatibility of metallic stent implants

Obiweluozor, Francis O.,Tiwari, Arjun Prasad,Lee, Jun Hee,Batgerel, Tumurbaatar,Kim, Ju Yeon,Lee, Dohee,Park, Chan Hee,Kim, Cheol Sang Elsevier 2019 Materials science & engineering. C, Materials for Vol.99 No.-

<P><B>Abstract</B></P> <P>Here we developed a semi-interpenetrating network (IPN) hydrogel obtained by free radical polymerization to fabricate a coated stent with the aim of incorporating a natural topography present in the human body to improve biological activity. The method involves sandwiching a bare metal stent in the semi-IPN hydrogel via solution cast molding. The bio-functionality of the membrane could be tuned by incorporating Polydopamine into the matrix, and also the mechanical property was optimized by choosing an adequate concentration of acrylamide. The coating containing polydopamine hydrogel showed good mechanical stability under continuous flow condition, as demonstrated by crimping and deployment into a catheter without damage. Stent polymer bonding was enhanced via polydopamine incorporation in the matrix. The non-thrombogenicity of the coating containing hydrogel was confirmed through dynamic hemocompatibility studies in vitro. Vascular simulations, including other biomechanical performance, like durability testing, radial strength, and recoil, were demonstrated. The dopamine containing hydrogel membrane (DCHM) was found to promote cell material interaction due to the ability of the catechol to bind protein and induce HUVECs cytoplasmic spreading, proliferation, and migration, with reduced smooth muscle cell (SMCs) activity. SMCs inhibition correlated well with the amount of incorporated catechol in the matrix. Our results show that this material used as coated stent could be more effective in suppressing platelet aggregation with improved haemocompatibility/biocompatibility for faster re-endothelialization than bare metal stent (BMS).</P> <P><B>Highlights</B></P> <P> <UL> <LI> 2D modeling of hydrogel coated stent for improved hemodynamics in contrast to bare metal stent was proposed. </LI> <LI> Incorporating PU as a second network in the IPN hydrogel greatly improve the mechanical property. </LI> <LI> The fabricated membrane creates a stable coating that enable delivery via non-invasive approach (catheter). </LI> <LI> Incorporation of Polydopamine in the matrix enhance HUVECs viability/ proliferation and suppresses SMCs viability. </LI> </UL> </P>

On-line Observation of Hydrogels during Swelling and LCST-induced changes

Hashmi, Saud,Obiweluozor, Francis,GhavamiNejad, Amin,Vatankhah-Varnoosfaderani, Mohammad,Stadler, Florian J. 한국유변학회 2012 Korea-Australia rheology journal Vol.24 No.3

A new technique for the online observation of rheological data of hydrogels during experiments involving significant volume changes is proposed. In order to accommodate for large volume changes, the gap has to be force controlled and continuously adjusted to the current sample height. Furthermore, the force control also has to ensure the adhesion of the sample to the geometry. For smaller volume changes, it is also possible to employ experiments with constant gap. Due to the volume change, the sample is not clearly defined with respect to the open surfaces in a parallel plate geometry, which leads to too high values, which, however, can be compensated for properly.

Supramolecular Interaction Controlled Diffusion Mechanism and Improved Mechanical Behavior of Hybrid Hydrogel Systems of Zwitterions and CNT

Hashmi, Saud,GhavamiNejad, Amin,Obiweluozor, Francis O.,Vatankhah-Varnoosfaderani, Mohammad,Stadler, Florian J. American Chemical Society 2012 Macromolecules Vol.45 No.24

<P>Hybrid hydrogels of poly(<I>N</I>-isopropylacrylamide) (pNIPAM) containing carboxylate carbon nanotubes (CNTs) and/or zwitterions are synthesized by free radical polymerization. The supramolecular interactions among zwitterionic monomers and CNTs influence the mechanical properties and diffusion mechanism in hybrid hydrogel systems. These supramolecular interactions and response behavior of hybrid hydrogels were tested mechanically and with respect to their swelling characteristics. Hybrid hydrogels of pNIPAM and CNT or pNIPAM, zwitterions, and CNT follow a Fickian diffusion behavior, while adding zwitterions leads to an anomalous triple-stage swelling behavior and stiffening of the gel due to the interactions of the zwitterions with each other, which significantly increase the viscous dissipation and change the microscopic structure. While CNT itself stiffens the gel and slightly increases the diffusion speed, it complexes zwitterions, which leads to a novel property profile that is both potentially antibiotic and electrically conductive. CNT affords a relaxation process at long relaxation times, while zwitterion attachment and detachment lead to dissipation predominantly at high frequencies. Dynamic rheological measurements were performed during swelling of these complex materials.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/mamobx/2012/mamobx.2012.45.issue-24/ma301366h/production/images/medium/ma-2012-01366h_0014.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ma301366h'>ACS Electronic Supporting Info</A></P>

Drug release and kinetic models of anticancer drug (BTZ) from a pH-responsive alginate polydopamine hydrogel: Towards cancer chemotherapy

Rezk, Abdelrahman I.,Obiweluozor, Francis O.,Choukrani, Ghizlane,Park, Chan Hee,Kim, Cheol Sang ELSEVIER 2019 INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES Vol.141 No.-

<P><B>Abstract</B></P> <P>A pH-sensitive polymeric carrier was developed in this study for local delivery of anticancer drug bortezomib (BTZ) to cancer cells. Our strategy is based on the conjugation of BTZ to polymeric carriers containing catechol groups, which are considered to release BTZ selectively in cancer cells. In this study we used alginate-conjugated polydopamine as a building block polymer. The catechol moiety of polydopamine binds to the boronic acid group of BTZ drug and release the drug molecules in a pH-dependent method. Cancer tissue has acidic environment where BTZ dissociate from the catechol group of polydopamine to control the release of the free drug. Mathematical equation models were used to clarify the mechanism of drug release. The release profile fitted first order with correlation coefficient (R<SUP>2</SUP> = 0.98), the release mechanism was studied using Korsmeyer–Peppas, Higuchi, Hixson-Crowell, and Kopcha models. We revealed the release mechanism follows non-fickian and diffusion was the dominant mechanism while small portion contributed to erosion. The pH-sensitive mechanism controls the release of BTZ in targeted cancer cells, hence developing a novel idea that is applicable in future towards other boronic acid-containing drugs to treat various kinds of health challenges.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The AlgPD-BTZ hydrogel presented a chemo selective approach for cancer chemotherapy. </LI> <LI> Sustained release profile of BTZ in pH dependent manner </LI> <LI> In-depth study of kinetics and mechanism of drug release </LI> <LI> The AlgPD-BTZ hydrogel shows remarkable cytotoxicity to cancer cells. </LI> </UL> </P>

Extracorporeal circulation models in small animals: beyond the limits of preclinical research

Mukhammad Kayumov,Reverien Habimana,김도완,Francis O Obiweluozor,정인석,조화진 대한중환자의학회 2023 Acute and Critical Care Vol.38 No.1

Extracorporeal membrane oxygenation (ECMO) use has remarkably increased in recent years. Al- though ECMO has become essential for patients with refractory cardiac and respiratory failure, ex- tracorporeal circulation (ECC) is associated with significant complications. Small-animal models of ECC have been developed and widely used to better understand ECC-induced pathophysiology. This review article summarizes the development of small-animal ECC models, including the animal spe- cies, circuit configuration, priming, perioperative procedures, cannulation, and future perspectives of small-animal ECMO models.

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.