Jaesoon Choi

The enhancement of mature vessel formation and cardiac function in infarcted hearts using dual growth factor delivery with self-assembling peptides

For successful treatment of myocardial infarction (MI), it is important to prevent cardiac fibrosis and maintain cardiac function by protecting cardiomyocytes and inducing angiogenesis. To establish functional and stable vessels, various growth factors, ones stimulating both endothelial cells (EC) and vascular smooth muscle cells (VSMC), are required. Self-assembling peptides form fibers (<10 nm) and provide 3-dimensional microenvironments that can recruit EC and VSMC to promote vascularization and long-term delivery of growth factors. Here we demonstrate myocardial protection of infarcted heart using dual growth factor delivery with self-assembling peptides. After coronary artery ligation in rats, growth factors (PDGF-BB and FGF-2) with self-assembling peptides were injected. There were 6 rats in each group. Hearts were harvested at 4 and 8 weeks for functional and histological analysis. Infarct size and cardiomyocyte apoptosis in dual growth factors along with self-assembling peptides group were dramatically reduced compared to sham. The capillary and arterial density of this group recovered with angiogenic synergism and cardiac functions had almost recovered. In conclusion, dual growth factors along with self-assembling peptides lead to myocardial protection, stable vessel formation, and improvement in cardiac function.

In vivo evaluation of MMP sensitive high-molecular weight HA-based hydrogels for bone tissue engineering.

Hyaluronic acid (170 kDa)-based hydrogel was synthesized using acrylated hyaluronic acid (HA) and matrix metalloproteinase (MMP) sensitive HA-based hydrogels were then prepared by conjugation with two different peptides: cell adhesion peptides containing integrin-binding domains (Arg-Gly-Asp: RGD) and a cross-linker with MMP degradable peptides to mimic the remodeling characteristics of natural extracellular matrices by cell-derived MMPs. Mechanical properties of these hydrogels were evaluated with different weight percentages (2.5 and 3.5 wt %) by measuring elastic modulus, viscous modulus, and swelling ratio. Human mesenchymal stem cells (hMSCs) were then cultured in MMP-sensitive or insensitive HA-based hydrogels and/or immobilized cell adhesive RGD peptides in vitro. Actin staining and image analysis proved that cells cultured in the MMP-sensitive hydrogel with RGD peptides showed extensive cell spreading and sprouting. Gene expression analysis showed that bone specific genes such as alkaline phosphatase, osteocalcin, and osteopontin increased in MMP-sensitive hydrogels as biomolecules such as BMPs and cells were added in the gels. For in vivo calvarial defect regeneration, five different samples (MMP insensitive hydrogel, MMP sensitive hydrogel, MMP sensitive hydrogel with BMP-2, MMP sensitive hydrogel with hMSC, and MMP sensitive hydrogel with BMP-2 and hMSC) were prepared. After 4 weeks of implantation, the Masson-Trichrome staining and micro computed tomography scan results demonstrated that the MMP sensitive hydrogels with BMP-2 and hMSCs have the highest mature bone formation. The MMP sensitive HA-based hydrogel could become useful scaffolds in bone tissue engineering with improvements on tissue remodeling rates and regeneration activity.

Sodium Alginate Hydrogel‐Based Bioprinting Using a Novel Multinozzle Bioprinting System

Bioprinting is a technology for constructing bioartificial tissue or organs of complex three-dimensional (3-D) structure with high-precision spatial shape forming ability in larger scale than conventional tissue engineering methods and simultaneous multiple components composition ability. It utilizes computer-controlled 3-D printer mechanism or solid free-form fabrication technologies. In this study, sodium alginate hydrogel that can be utilized for large-dimension tissue fabrication with its fast gelation property was studied regarding material-specific printing technique and printing parameters using a multinozzle bioprinting system developed by the authors. A sodium alginate solution was prepared with a concentration of 1% (wt/vol), and 1% CaCl(2) solution was used as cross-linker for the gelation. The two materials were loaded in each of two nozzles in the multinozzle bioprinting system that has a total of four nozzles of which the injection speed can be independently controlled. A 3-D alginate structure was fabricated through layer-by-layer printing. Each layer was formed through two phases of printing, the first phase with the sodium alginate solution and the second phase with the calcium chloride solution, in identical printing pattern and speed condition. The target patterns were lattice shaped with 2-mm spacing and two different line widths. The nozzle moving speed was 6.67 mm/s, and the injection head speed was 10 µm/s. For the two different line widths, two injection needles with inner diameters of 260 and 410 µm were used. The number of layers accumulated was five in this experiment. By varying the nozzle moving speed and the injection speed, various pattern widths could be achieved. The feasibility of sodium alginate hydrogel free-form formation by alternate printing of alginate solution and sodium chloride solution was confirmed in the developed multinozzle bioprinting system.

A Three-Dimensional Bioprinting System for Use With a Hydrogel-Based Biomaterial and Printing Parameter Characterization

Bioprinting is an emerging technology for constructing tissue or bioartificial organs with complex three-dimensional (3D) structures. It provides high-precision spatial shape forming ability on a larger scale than conventional tissue engineering methods, and simultaneous multiple components composition ability. Bioprinting utilizes a computer-controlled 3D printer mechanism for 3D biological structure construction. To implement minimal pattern width in a hydrogel-based bioprinting system, a study on printing characteristics was performed by varying printer control parameters. The experimental results showed that printing pattern width depends on associated printer control parameters such as printing flow rate, nozzle diameter, and nozzle velocity. The system under development showed acceptable feasibility of potential use for accurate printing pattern implementation in tissue engineering applications and is another example of novel techniques for regenerative medicine based on computer-aided biofabrication system.

Development of a force-reflecting robotic platform for cardiac catheter navigation.

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.

Haptic virtual fixture for robotic cardiac catheter navigation.

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.

An intelligent remote monitoring system for artificial heart

A web-based database system for intelligent remote monitoring of an artificial heart has been developed. It is important for patients with an artificial heart implant to be discharged from the hospital after an appropriate stabilization period for better recovery and quality of life. Reliable continuous remote monitoring systems for these patients with life support devices are gaining practical meaning. The authors have developed a remote monitoring system for this purpose that consists of a portable/desktop monitoring terminal, a database for continuous recording of patient and device status, a web-based data access system with which clinicians can access real-time patient and device status data and past history data, and an intelligent diagnosis algorithm module that noninvasively estimates blood pump output and makes automatic classification of the device status. The system has been tested with data generation emulators installed on remote sites for simulation study, and in two cases of animal experiments conducted at remote facilities. The system showed acceptable functionality and reliability. The intelligence algorithm also showed acceptable practicality in an application to animal experiment data.

Development of a Mobile Phone Based e-Health Monitoring Application

The use of Electrocardiogram (ECG) system is important in primary diagnosis and survival analysis of the heart diseases. Growing portable mobile technologies have provided possibilities for medical monitoring for human vital signs and allow patient move around freely. In this paper, a mobile health monitoring application program is described. This system consists of the following sub-systems: real-time signal receiver, ECG signal processing, signal display in mobile phone, and data management as well five user interface screens. We verified the signal feature detection using the MIT-BIH arrhythmia database. The detection algorithms were implemented in the mobile phone application program. This paper describes the application system that was developed and tested successfully.

A Comparative Reliability and Performance Study of Different Stent Designs in Terms of Mechanical Properties: Foreshortening, Recoil, Radial Force, and Flexibility

This study seeks to improve the mechanical performance of stents by conducting reliability performance testing and finite element method (FEM)-based simulations for coronary stents. Three commercially available stent designs and our own new design were tested to measure the factors affecting performance, specifically foreshortening, recoil, radial force, and flexibility. The stents used in the present experiments were 3 mm in working diameter and 18 mm of working length. The results of the experiments indicate that the foreshortening of stents A, B, C, and our new design, D, was equivalent to 2.25, 0.67, 0.46, and 0.41%, respectively. The recoil of stents A, B, C, and D was 6.00, 4.35, 3.50, and 4.36%, respectively. Parallel plate radial force measurements were A, 3.72 ± 0.28 N; B, 3.81 ± 0.32 N; C, 4.35 ± 0.18 N; and D, 4.02 ± 0.24 N. Radial forces determined by applying uniform pressure in the circumferential direction were A, 28.749 ± 0.81 N; B, 32.231 ± 1.80 N; C, 34.522 ± 3.06 N; and D, 42.183 ± 2.84 N. The maximum force of crimped stent at 2.2-mm deflection was 1.01 ± 0.08 N, 0.82 ± 0.08 N, 0.92 ± 0.12 N, and 0.68 ± 0.07 N for each of stents A, B, C and D. The results of this study enabled us to identify several factors to enhance the performance of stents. In comparing these stents, we found that our design, stent D, which was designed by a collaborative team from seven universities, performed better than the commercial stents across all parameter of foreshortening, recoil, radial force, and flexibility.

Lapabot: a compact telesurgical robot system for minimally invasive surgery: part I. System description.

Abstract The applications of robotic minimally invasive surgery (MIS) have widened, providing new advantages such as augmented dexterity and telesurgery. However, current commercial robotic laparoscopic surgical systems still have aspects to be improved such as heavy and bulky systems not suitable for agile operations, large rotational radii of robot manipulator arms, limited remote control capacity, and absence of force feedback. We have developed a robotic laparoscopic surgical system that features compact slave manipulators. The system can simultaneously operate one laparoscope arm and up to four instrument arms. The slave robot is controlled remotely through an Ethernet network and is ready for telesurgery. The developed surgical robot has sufficient workspace to perform general MIS and has been shown to provide acceptable motion tracking control performance.