Comparison of Angiogenic Activities of Three Neuropeptides, Substance P, Secretoneurin, and Neuropeptide Y Using Myocardial Infarction

Yongdoo Park 한국조직공학과 재생의학회 2018 조직공학과 재생의학 Vol.15 No.4

BACKGROUND: The interplay between neurogenesis and angiogenesis is crucial during the development mediated by neuro-angiogenic morphogens. In particular, the angiogenic activity of neuropeptides and their role in tissue regeneration have long been investigated for better understanding of their biological mechanisms and further applications. However, there have been few studies for direct comparison of angiogenic activities of neuropeptides for in vitro and in vivo models. In this study, we report that direct comparison of the angiogenic activities of neuropeptide Y, secretoneurin, and substance P (SP) immobilized on hydrogels in in vitro and in vivo experiments. METHODS: A hyaluronic acid-based hydrogel is prepared by utilizing acrylated hyaluronic acid and thiolated peptides as a crosslinker and angiogenic factors, respectively. Angiogenic activities of three neuropeptides are evaluated not only by in vitro angiogenic and gene expression assays, but also by an in vivo chronic myocardial infarction model. RESULTS: The comparison of in vitro angiogenic activities of three peptides demonstrates that the SP-immobilized hydrogel shows a higher degree of cell network formation and angiogenic-specific genes than those of the other peptides and the control case. In addition, a three-dimensional angiogenic assay illustrates that more sprouting is observable in the SP group. Evaluation of regenerative activity in the chronic myocardial infarction model reveals that all three peptideimmobilized hydrogels induce increased cardiac function as well as structural regeneration. Among all the cases, the SP group provided the highest regenerative activity both in vitro and in vivo. CONCLUSION: In our comparison study, the SP-immobilized hydrogel shows the highest angiogenic activity and tissue regeneration among the test groups. This result suggests that nerve regeneration factors help angiogenesis in damaged tissues, which also highlights the importance of the neuro-angiogenic peptides as an element of tissue regeneration.

Development of a Force‐Reflecting Robotic Platform for Cardiac Catheter Navigation

Park, Jun Woo,Choi, Jaesoon,Pak, Hui‐,Nam,Song, Seung Joon,Lee, Jung Chan,Park, Yongdoo,Shin, Seung Min,Sun, Kyung Blackwell Publishing Inc 2010 Artificial Organs Vol.34 No.11

<P><B>Abstract</B></P><P>Electrophysiological catheters are used for both diagnostics and clinical intervention. To facilitate more accurate and precise catheter navigation, robotic cardiac catheter navigation systems have been developed and commercialized. The authors have developed a novel force‐reflecting robotic catheter navigation system. The system is a network‐based master–slave configuration having a 3‐degree of freedom robotic manipulator for operation with a conventional cardiac ablation catheter. The master manipulator implements a haptic user interface device with force feedback using a force or torque signal either measured with a sensor or estimated from the motor current signal in the slave manipulator. The slave manipulator is a robotic motion control platform on which the cardiac ablation catheter is mounted. The catheter motions—forward and backward movements, rolling, and catheter tip bending—are controlled by electromechanical actuators located in the slave manipulator. The control software runs on a real‐time operating system‐based workstation and implements the master/slave motion synchronization control of the robot system. The master/slave motion synchronization response was assessed with step, sinusoidal, and arbitrarily varying motion commands, and showed satisfactory performance with insignificant steady‐state motion error. The current system successfully implemented the motion control function and will undergo safety and performance evaluation by means of animal experiments. Further studies on the force feedback control algorithm and on an active motion catheter with an embedded actuation mechanism are underway.</P>

Tissue Regeneration using hyaluronic acid based based hydrogel

Yongdoo Park 한국고분자학회 2007 한국고분자학회 학술대회 연구논문 초록집 Vol.2007 No.4

Haptic Virtual Fixture for Robotic Cardiac Catheter Navigation

Park, Jun Woo,Choi, Jaesoon,Park, Yongdoo,Sun, Kyung Blackwell Publishing Inc 2011 Artificial Organs Vol.35 No.11

<P><B>Abstract</B></P><P>In manual or robot‐assisted catheter intervention, excessive manipulation force may cause tissue perforation. Using images acquired by an imaging device routinely used for catheter interventions such as X‐ray fluoroscopy, the structure and size of blood vessels and the relative position of the catheter tip inside the vessel can be obtained. To prevent collision of the catheter tip and the vessel wall, vision‐assisted control methods using forbidden‐region virtual fixture (FRVF) technique can be utilized and an experimental implementation has been performed in this study. A master–slave configured robotic platform for cardiac catheter was used for this study. The robotic master handle can provide haptic rendering to the user. A vessel phantom model mimicking human vasculature for the inner radii was fabricated for simulated intervention experiments. A digital optical camera was used for image acquisition. After the vessel phantom and the catheter tip were segmented, distance between the vessel centerline and the catheter tip was calculated and the forbidden region that the catheter tip should keep away from was set for the safe catheter manipulation. Virtual force generation algorithm was implemented for feeding the signal indicating the catheter tip penetrating into the forbidden region back to the user in the robotic master handle. To validate the suggested method, in vitro experiments were conducted. Through a chain of image filtering procedures including edge detection, the catheter tip and the vessel wall were able to be well segmented. The virtual force generator worked appropriately. The developed FRVF technique could provide helpful auxiliary information to clinicians for safer manipulation of catheters in cardiac catheterization procedures.</P>

A ratiometric fluorescent probe based on a BODIPY–DCDHF conjugate for the detection of hypochlorous acid in living cells

Park, Jeesook,Kim, Hyunjin,Choi, Yongdoo,Kim, Youngmi The Royal Society of Chemistry 2013 The Analyst Vol.138 No.12

<P>A colorimetric and ratiometric fluorescent probe consisting of a boron-dipyrromethene (BODIPY) dye conjugated with a 2-dicyanomethylene-3-cyano-2,5-dihydrofuran (DCDHF) group has been designed for the selective and sensitive detection of HOCl/OCl<SUP>−</SUP><I>via</I> oxidative cleavage of an alkene linker between BODIPY and DCDHF.</P> <P>Graphic Abstract</P><P>A colorimetric and ratiometric fluorescent probe consisting of a boron-dipyrromethene (BODIPY) dye conjugated with 2-dicyanomethylene-3-cyano-2,5-dihydrofuran (DCDHF) has been designed for detection of HOCl <I>via</I> oxidative cleavage of an alkene linker between BODIPY and DCDHF. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c3an36820c'> </P>

Polypyrrole-based nanotheranostics for activatable fluorescence imaging and chemo/photothermal dual therapy of triple-negative breast cancer

Park, Dongjin,Ahn, Kyung-Ohk,Jeong, Kyung-Chae,Choi, Yongdoo IOP 2016 Nanotechnology Vol.27 No.18

<P>Here, we fabricated polypyrrole nanoparticles (PPys) (termed HA10-PPy, HA20-PPy, and HA40-PPy) doped with different average molecular weight hyaluronic acids (HAs) (10, 20, and 40 kDa, respectively), and evaluated the effect of molecular weight of doped HA on photothermal induction, fluorescence quenching, and drug loading efficiencies. Doxorubicin-loaded HA-doped PPys (DOX@HA–PPys) could be used for imaging and therapy of triple-negative breast cancer (TNBC). Fluorescence turn-on, stimuli-responsive drug release, and photo-induced heating of DOX@HA–PPys enabled not only activatable fluorescence imaging but also subsequent chemo/photothermal dual therapy for TNBC. In particular, we illustrated the potential usefulness of the photothermal effect of the nanoparticles for overcoming chemoresistance in TNBC.</P>

Hyaluronic acid–polypyrrole nanoparticles as pH-responsive theranostics

Park, Dongjin,Cho, Youngnam,Goh, Sung-Ho,Choi, Yongdoo The Royal Society of Chemistry 2014 Chemical communications Vol.50 No.95

<P>Doxorubicin-loaded hyaluronic acid–polypyrrole nanoparticles were developed for pH-responsive activatable fluorescence imaging and therapy of proliferating macrophages.</P> <P>Graphic Abstract</P><P>Doxorubicin-loaded hyaluronic acid–polypyrrole nanoparticles as smart theranostic agents for proliferating macrophages. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c4cc06349j'> </P>

A boronate-based fluorescent probe for the selective detection of cellular peroxynitrite

Kim, Jiyoung,Park, Jeesook,Lee, Hawon,Choi, Yongdoo,Kim, Youngmi The Royal Society of Chemistry 2014 Chemical communications Vol.50 No.66

<P>A boronate-based fluorescent probe <B>1</B> for the selective monitoring of intracellular peroxynitrite has been developed. The probe takes advantage of the fast reaction of an arylboronate group with peroxynitrite, yielding a corresponding phenol that undergoes spontaneous subsequent reactions to produce a strongly fluorescent product associated with a large turn-on signal.</P> <P>Graphic Abstract</P><P>A boronate-based fluorescent probe <B>1</B> for the selective monitoring of intracellular peroxynitrite has been developed. The probe takes advantage of the fast reaction of an arylboronate group with peroxynitrite, yielding a corresponding phenol that undergoes spontaneous subsequent reactions to produce a strongly fluorescent product associated with a large turn-on signal. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c4cc02943g'> </P>

Gold Nanorod−Photosensitizer Complex for Near-Infrared Fluorescence Imaging and Photodynamic/Photothermal Therapy <i>In Vivo</i>

Jang, Boseung,Park, Jin-Young,Tung, Ching-Hsuan,Kim, In-Hoo,Choi, Yongdoo American Chemical Society 2011 ACS NANO Vol.5 No.2

<P>A gold nanorod (GNR)−photosensitizer complex was developed for noninvasive near-infrared fluorescence imaging and cancer therapy. We showed that (a) fluorescence emission and singlet oxygen generation by AlPcS<SUB>4</SUB> were quenched after complex formation with GNRs; (b) 4-fold greater intracellular uptake and better <I>in vitro</I> phototoxicity were observed in GNR−AlPcS<SUB>4</SUB>-treated cells than in free AlPcS<SUB>4</SUB>-treated cells; and (c) after intravenous injection of the GNR−AlPcS<SUB>4</SUB> complex, tumor sites were clearly identified on near-infrared fluorescence images as early as 1 h after injection. The tumor-to-background ratio increased over time and was 3.7 at 24 h; tumor growth reduced by 79% with photodynamic therapy (PDT) alone and by 95% with dual photothermal therapy (PTT) and PDT. This novel multifunctional nanomedicine may be useful for near-infrared fluorescence imaging and PTT/PDT in various cancers.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2011/ancac3.2011.5.issue-2/nn102722z/production/images/medium/nn-2010-02722z_0003.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nn102722z'>ACS Electronic Supporting Info</A></P>

Characterization of low-molecular-weight hyaluronic acid-based hydrogel and differential stem cell responses in the hydrogel microenvironments

Kim, Jungju,Park, Yongdoo,Tae, Giyoong,Lee, Kyu Back,Hwang, Chang Mo,Hwang, Soon Jung,Kim, In Sook,Noh, Insup,Sun, Kyung Wiley Subscription Services, Inc., A Wiley Company 2009 Journal of biomedical materials research. Part A Vol.a88 No.4

<P>Hyaluronic acid is a natural glycosaminoglycan involved in biological processes. Low-molecular-weight hyaluronic acid (10 and 50 kDa)-based hydrogel was synthesized using derivatized hyaluronic acid. Hyaluronic acid was acrylated by two steps: (1) introduction of an amine group using adipic acid dihydrazide, and (2) acrylation by N-acryloxysuccinimide. Injectable hyaluronic acid-based hydrogel was prepared by using acrylated hyaluronic acid and poly(ethylene glycol) tetra-thiols via Michael-type addition reaction. Mechanical properties of the hydrogel were evaluated by varying the molecular weight of acrylated hyaluronic acid (10 and 50 kDa) and the weight percent of hydrogel. Hydrogel based on 50-kDa hyaluronic acid showed the shortest gelation time and the highest complex modulus. Next, human mesenchymal stem cells were cultured in cell-adhesive RGD peptide-immobilized hydrogels together with bone morphogenic protein-2 (BMP-2). Cells cultured in the RGD/BMP-2-incorporated hydrogels showed proliferation rates higher than that of control or RGD-immobilized hydrogels. Real-time RT-PCR showed that the expression of osteoblast marker genes such as CBFα1 and alkaline phosphatase was increased in hyaluronic acid-based hydrogel, and the expression level was dependent on the molecular weight of hyaluronic acid, RGD peptide, and BMP-2. This study indicates that low-molecular-weight hyaluronic acid-based hydrogel can be applied to tissue regeneration as differentiation guidance materials of stem cells. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009</P>