Dohyung Lim

Heparin‐Coated Gold Nanoparticles for Liver‐Specific CT Imaging

Since computed tomography (CT) was developed and its resolution, sensitivity, and scan speed rapidly improved, the use of CT in the diagnosis of hepatic disease has been evaluated by various investigators. In particular, liver-specific X-ray CT imaging has attracted much attention in cancer diagnosis and cancer treatment because liver metastases are a common occurrence in the history of a patient affected by various cancers. The liver is the organ most frequently involved in metastases due to its high volume of blood flow, the suitable size of sinusoids for trapping metastatic cells, and rich environment for rapid growth. The sensitivity of liver imaging needs to be guaranteed in cancer detection because diagnosis of liver metastasis at an early stage mainly relies on imaging and all liver metastases begin with a microscopic-sized tumor. However, in CT imaging, the detection of liver lesions is impossible without the use of contrast-enhancing agents, although, even then, the problem of distinguishing between small vessels and small liver tumors is an issue. For this reason, the demand for a tissue-specific X-ray contrast agent has increased, although there are a few products available they have limitations for clinical application. Although low-molecular-weight iodinated contrast agents are generally used in CT imaging, they have serious limitations in clinical applications due to their low liver uptake, rapid renal excretion, and lack of membrane permeation; this leads to renal toxicity and high viscosity of the injectable formulation. To overcome the undesirable pharmacokinetics and limitations, low-molecular-weight iodinates have been chemically conjugated to high-molecular-weight polymers or encapsulated into liposomes and polymeric micelles. These macromolecular and nanosized contrast agents display enhanced blood-circulating characteristics in vivo as well as providing liver-specific CT images. However, they still show a lower imaging resolution with respect to differentiating liver tissues from other vessels, organs, and cancers because iodine-based contrast agents inherently possess a lower X-ray absorption coefficient. Another novel inorganic nanoparticle-based CT contrast agent has been proposed. Polymer-coated bismuth sulfide (Bi2S3) nanoparticles showed high X-ray absorption compared with iodinated imaging agents, but their size and shape were not easy to [a] I.-C. Sun, J. H. Na, Dr. S. Lee, Dr. I.-C. Youn, Dr. K. Choi, Dr. I. C. Kwon, Dr. K. Kim Biomedical Research Center Korea Institute of Science and Technology 39-1 Hawolgok-dong, Seongbuk-gu, Seoul, 136-791 (Korea) Fax: (+82)2-958-5909 E-mail : kim@kist.re.kr [b] D.-K. Eun, Dr. C.-H. Ahn Research Institute of Advanced Materials (RIAM) Department of Materials Science and Engineering Seoul National University San 56-1, Sillim, Gwanak, Seoul, 151-744 (Korea) Fax: (+82)2-883-8197 E-mail : chahn@snu.ac.kr [c] I.-J. Kim Department of Chemistry, College of Science, Korea University Anam-dong, Seongbuk-gu, Seoul 136-791 (Korea) [d] Dr. C.-Y. Ko, Dr. H.-S. Kim Department of Biomedical Engineering, Yonsei University Wonju, Ganwondo, 220-710 (Korea) [e] Dr. D. Lim Silver Technology Center, Korea Institute of Industrial Technology 35-5 Hongcheon, Ipjang, Cheonan, Chungnam (Korea) [f] Dr. P. B. Messersmith Biomedical Engineering, Northwestern University 2145 Sheridan Road, Evanstron, IL 60208 (USA) [g] Dr. T. G. Park Department of Biological Sciences Korea Advanced Institute of Science Technology Daejeon 305-701 (Korea) [h] Dr. S. Y. Kim Department of Otolaryngology-Head and Neck Surgery Asan Medical Center, College of Medicine, University of Ulsan Seoul 138-736 (South Korea) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.200902344.

Finite Element Analysis for Evaluation of Pressure Ulcer on the Buttock: Development and Validation

The interface pressure is currently the only clinical tool to estimate the risk of sitting-related pressure ulcers. However, it provides little information on the loading condition in deep tissues. We present a comprehensive 3-D finite element (FE) model for human buttocks with the consideration of the joint configuration and realistic boundary conditions in a sitting posture. Sitting induced soft tissue deformation, internal pressure, and von-Mises stress were computed. The FE model was well validated qualitatively using actual displacement obtained from magnetic resonance imaging (MRI) images. FE analysis demonstrated that the deformation induced by sitting pressure was substantially different among muscle, fat, and skin. The deformation of the muscle varied with location and the maximum was seen in the regions underneath the bony prominence of ischial tuberosity. In these regions, the range of compressive pressure was 65-80 kPa, 50-60 kPa, and 55-65 kPa, for skin, fat, and muscle, respectively. The von-Mises stress distribution had a similar pattern. In conclusion, this study suggests a new methodology for the development and validation of FE models for investigating the risk of sitting-related soft tissue injury. The proposed model may provide researchers and therapists with a powerful technique for evaluating the effectiveness of various postural modulations in preventing deep tissue ulcers.

Limitations of Imageless Computer-Assisted Navigation for Total Hip Arthroplasty

We prospectively evaluated acetabular cup placement in total hip arthroplasty with an imageless computer navigation system or using conventional manual technique. The achieved cup orientation in the manual group had substantially larger variances and greater placement error than the navigation cases. The use of navigation was abandoned in 3 cases because of excessive pelvic tilt and unreliable registration of the pelvis. Computer navigation system helped improve the accuracy of the acetabular cup placement for total hip arthroplasty in this study. The variation between the intraoperative navigation readings and the computed tomographic values suggests that relying on palpation of bony landmarks through drapes and tissue is a limitation of this method. Further, the variation in pelvic tilt has an effect on cup placement that requires further studies.

Validation of a computer navigation system and a CT method for determination of the orientation of implanted acetabular cup in total hip arthroplasty: A cadaver study

BACKGROUND Successful hip reconstruction to restore the normal hip biomechanics requires precise placement of implants. Computer assisted navigation in total hip arthroplasty has been proposed to have the potential to help achieve a high accuracy in implant placement. The goal of the study was to evaluate the accuracy of an imageless computer navigation system on cadavers and to validate a non-invasive computed tomography method for post-operative determination of acetabular cup orientation. METHODS Total hip arthroplasty was performed on seven cadaver hips with the aid of an imageless computer navigation system. The achieved cup orientation were recorded using three methods, (1) intra-operatively using the imageless computer navigation system, (2) post-operatively with direct bone digitization and (3) with a computed tomography based three dimensional model interpreted by three raters. Measurement from the direct bone digitization was taken as the gold standard to evaluate the other two methods. The intra-rater and inter-rater consistency of the computer tomography-model method were assessed by Cronbachs alpha determination. FINDINGS Compared with the cup orientation obtained from the direct bone digitization, the average difference for anteversion and abduction were 3.3 (3.5) degrees (P=0.045) and 0.6 (3.7) degrees , respectively, for navigation reading. The average differences for computer tomography-model for three raters were 0.5 (2.1) degrees , 0.8 (1.5) degrees and 3.2 (3.3) degrees (P=0.043) for anteversion and 0.4 (1.6) degrees , 0.3 (1.6) degrees and 2.1 (2.7) degrees for abduction. The intra-rater consistency ranged from 0.626 for a novice rater to over 0.97 for experience raters. The inter-rater consistency (including novice and experienced raters) was over 0.90. INTERPRETATION While the values for cup orientation determined with imageless computer navigation were comparable to those from direct bone and implant digitization, the measurement for anteversion obtained was not as accurate as that for abduction. The proposed computer tomography-model method has an excellent intra-rater consistency for experienced raters, as well as an excellent overall inter-rater consistency. The study confirms that a non-invasive computed tomography based model analysis can be used in clinical practice as a valid method for post-operatively evaluating the orientation of the acetabular component.

Suggestion of Potential Stent Design Parameters to Reduce Restenosis Risk driven by Foreshortening or Dogboning due to Non-uniform Balloon-Stent Expansion

The foreshortening or dogboning of a stent that occurs due to transient non-uniform balloon-stent expansion can induce a vascular injury, resulting in restenosis of the coronary artery. However, previous studies rarely considered the effects of transient non-uniform balloon expansion on analysis of the mechanical properties and behaviors of stents during stent deployment, nor did they determine design parameters to minimize the restenosis risk driven by foreshortening or dogboning. The aim of the current study was, therefore, to suggest potential design parameters capable of reducing the possibility of restenosis risk driven by foreshortening or dogboning through a comparative study of seven commercial stents using finite element (FE) analyses of a realistic transient non-uniform balloon-stent expansion process. The results indicate that using stents composed of opened unit cells connected by bend-shaped link structures, in particular the MAC Plus stent, and controlling the geometrical and morphological features of the unit cell strut or the link structure at the distal ends of stent may prevent restenosis risk caused by foreshortening or dogboning. This study provides a first look at the realistic transient non-uniform balloon-stent expansion by investigating the mechanical properties, behaviors, and design parameters capable of reducing the possibility of restenosis risk induced by the foreshortening or the dogboning.

Relationship between nutrition factors and osteopenia: Effects of experimental diets on immature bone quality

To investigate the influence of experimental diets on morphological and mechanical characteristics of immature bone, this study thoroughly examined the nutrition-bone connection. A non-destructive evaluation method involving high-resolution in-vivo micro-computed tomography and finite element (FE) analysis was used to investigate the relationship between obesity and osteopenia-two disorders of body composition. Correlation of nutritional deficiency with bone characteristics was also investigated. Some recent studies have shown that both obesity and osteopenia share several common genetic and environmental factors. However, there have been few studies correlating these pathologies in-vivo from a structural and biomechanical point of view. In the present study, detailed changes in morphological and mechanical characteristics of trabecular bone architecture were detected and tracked by longitudinal studies of morphometric parameters and simulated compression testing. Rats were randomized into three groups: overeaten diet (OD) for formation of obesity, normal diet (ND), and restricted diet (RD) in which rats received 65% of the normal diet. In the OD and ND groups, all structural parameters changed significantly (p<0.05). The degree of alteration in the structural parameters of the ND group was similar to that of the RD group (p<0.05). In simulated compression tests using FE models, the effective modulus of the OD group significantly decreased, depending on measuring time (p<0.05), whereas that of the ND and RD groups significantly increased (p>0.05). The key finding of the present study is that fat mass is morphologically and mechanically inversely correlated with bone mass when the mechanical loading effects of greater body weight on bone mass are applied.

Evaluation of a new sitting concept designed for prevention of pressure ulcer on the buttock using finite element analysis.

Excessive compressive load induces pressure related soft tissue damage, i.e. pressure ulcer (PU), in buttock area in wheelchair users. In solving this problem, our previous study has introduced a concept of Off-Loading sitting, which partially removes the ischial support to reduce pressure under buttocks. However, the effect of this sitting concept has only been evaluated using the interface pressure and tissue perfusion measurements. The objective of this investigation was to evaluate the Off-Loading posture for its ability to reduce internal pressure and stress in deep buttock tissues. This evaluation was performed on a 3D finite element (FE) model which was established and validated in a sitting posture and has realistic material properties and boundary conditions. FE analysis in this study confirmed that the pressure relief provided by Off-Loading posture created profound effect in reducing the mechanical stress within deep tissues. It was concluded that Off-Loading posture may prove beneficial in preventing sitting related PU.

Low-intensity ultrasound stimulation prevents osteoporotic bone loss in young adult ovariectomized mice†

Osteoporosis is a disease characterized by low bone mass, increased bone fragility, and a greater risk for bone fracture. Currently, pharmacological intervention can generally aid in the prevention and treatment of osteoporosis, but these therapies are often accompanied by undesirable side effects. Therefore, alternative therapies that minimize side effects are necessary. Biophysical stimuli, especially low‐intensity ultrasound stimulation (LIUS), may be potential alternatives to drug‐based therapies for osteoporosis. Hence, we sought to address whether LIUS therapy can effectively prevent or treat osteoporotic bone loss induced by estrogen deficiency. LIUS (1.5 MHz frequency, 1.0 kHz pulse repetition on frequency, 30 mW/cm2 intensity, 200 µs pulse length) was applied to right tibiae of eight 14‐week‐old ovariectomized virgin ICR female mice for 20 min per day, 5 days per week, over a 6‐week period. Changes in 3D structural bone characteristics were detected using in vivo micro‐computed tomography. Left tibiae served as controls. Structural characteristics including bone volume/tissue volume, trabecular number, trabecular bone pattern factor, and mean polar moment inertia were significantly enhanced 6 weeks after LIUS compared to the control, nonstimulated group (p < 0.05). In particular, the bone volume/tissue volume in the region exposed directly to LIUS was significantly higher in the treated group (p < 0.05). These findings indicate that new bone formation may be activated or that bone structure may be maintained by LIUS, and that LIUS may be effective for preventing estrogen deficiency‐induced bone loss.

Use of the Microsoft Kinect system to characterize balance ability during balance training.

The risk of falling increases significantly in the elderly because of deterioration of the neural musculature regulatory mechanisms. Several studies have investigated methods of preventing falling using real-time systems to evaluate balance; however, it is difficult to monitor the results of such characterizations in real time. Herein, we describe the use of Microsoft’s Kinect depth sensor system to evaluate balance in real time. Six healthy male adults (25.5±1.8 years, 173.9±6.4 cm, 71.4±6.5 kg, and 23.6±2.4 kg/m2), with normal balance abilities and with no musculoskeletal disorders, were selected to participate in the experiment. Movements of the participants were induced by controlling the base plane of the balance training equipment in various directions. The dynamic motion of the subjects was measured using two Kinect depth sensor systems and a three-dimensional motion capture system with eight infrared cameras. The two systems yielded similar results for changes in the center of body mass (P>0.05) with a large Pearson’s correlation coefficient of γ>0.60. The results for the two systems showed similarity in the mean lower-limb joint angle with flexion–extension movements, and these values were highly correlated (hip joint: within approximately 4.6°; knee joint: within approximately 8.4°) (0.400.05). Large differences with a low correlation were, however, observed for the lower-limb joint angle in relation to abduction–adduction and internal–external rotation motion (γ<0.40) (P<0.05). These findings show that clinical and dynamic accuracy can be achieved using the Kinect system in balance training by measuring changes in the center of body mass and flexion–extension movements of the lower limbs, but not abduction–adduction and internal–external rotation.

Hyaluronic Acid/PLGA Core/Shell Fiber Matrices Loaded with EGCG Beneficial to Diabetic Wound Healing

During the last few decades, considerable research on diabetic wound healing strategies has been performed, but complete diabetic wound healing remains an unsolved problem, which constitutes an enormous biomedical burden. Herein, hyaluronic acid (HA)/poly(lactic-co-glycolic acid, PLGA) core/shell fiber matrices loaded with epigallocatechin-3-O-gallate (EGCG) (HA/PLGA-E) are fabricated by coaxial electrospinning. HA/PLGA-E core/shell fiber matrices are composed of randomly-oriented sub-micrometer fibers and have a 3D porous network structure. EGCG is uniformly dispersed in the shell and sustainedly released from the matrices in a stepwise manner by controlled diffusion and PLGA degradation over four weeks. EGCG does not adversely affect the thermomechanical properties of HA/PLGA-E matrices. The number of human dermal fibroblasts attached on HA/PLGA-E matrices is appreciably higher than that on HA/PLGA counterparts, while their proliferation is steadily retained on HA/PLGA-E matrices. The wound healing activity of HA/PLGA-E matrices is evaluated in streptozotocin-induced diabetic rats. After two weeks of surgical treatment, the wound areas are significantly reduced by the coverage with HA/PLGA-E matrices resulting from enhanced re-epithelialization/neovascularization and increased collagen deposition, compared with no treatment or HA/PLGA. In conclusion, the HA/PLGA-E matrices can be potentially exploited to craft strategies for the acceleration of diabetic wound healing and skin regeneration.