Polydopamine-Assisted Osteoinductive Peptide Immobilization of Polymer Scaffolds for Enhanced Bone Regeneration by Human Adipose-Derived Stem Cells

Ko, Eunkyung,Yang, Kisuk,Shin, Jisoo,Cho, Seung-Woo American Chemical Society 2013 Biomacromolecules Vol.14 No.9

<P>Immobilization of osteoinductive molecules, including growth factors or peptides, on polymer scaffolds is critical for improving stem cell-mediated bone tissue engineering. Such molecules provide osteogenesis-stimulating signals for stem cells. Typical methods used for polymeric scaffold modification (e.g., chemical conjugation or physical adsorption), however, have limitations (e.g., multistep, complicated procedures, material denaturation, batch-to-batch inconsistency, and inadequate conjugation) that diminish the overall efficiency of the process. Therefore, in this study, we report a biologically inspired strategy to prepare functional polymer scaffolds that efficiently regulate the osteogenic differentiation of human adipose-derived stem cells (hADSCs). Polymerization of dopamine (DA), a repeated motif observed in mussel adhesive protein, under alkaline pH conditions, allows for coating of a polydopamine (pDA) layer onto polymer scaffolds. Our study demonstrates that predeposition of a pDA layer facilitates highly efficient, simple immobilization of peptides derived from osteogenic growth factor (bone morphogenetic protein-2; BMP-2) on poly(lactic-<I>co</I>-glycolic acid) (PLGA) scaffolds via catechol chemistry. The BMP-2 peptide-immobilized PLGA scaffolds greatly enhanced in vitro osteogenic differentiation and calcium mineralization of hADSCs using either osteogenic medium or nonosteogenic medium. Furthermore, transplantation of hADSCs using pDA-BMP-2-PLGA scaffolds significantly promoted in vivo bone formation in critical-sized calvarial bone defects. Therefore, pDA-mediated catechol functionalization would be a simple and effective method for developing tissue engineering scaffolds exhibiting enhanced osteoinductivity. To the best of our knowledge, this is the first study demonstrating that pDA-mediated surface modification of polymer scaffolds potentiates the regenerative capacity of human stem cells for healing tissue defect in vivo.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/bomaf6/2013/bomaf6.2013.14.issue-9/bm4008343/production/images/medium/bm-2013-008343_0011.gif'></P>

06. A Basic Study on the Evaluation of Early Childhood Environment Education: What and How Do We Measure?

( Eunkyung Ko ) 한국유아교육학회 2019 정기학술대회 논문집 Vol.2019 No.2

Synergistic effect of Bcl-2 and cyclin A2 on adverse recurrence-free survival in stage I non-small cell lung cancer.

Ko, Eunkyung,Kim, Yujin,Cho, Eun Yoon,Han, Jungho,Shim, Young Mog,Park, Joobae,Kim, Duk-Hwan Raven Press 2013 Annals of surgical oncology Vol.20 No.3

<P>The prognostic significance of cyclin A2 overexpression in non-small cell lung cancer (NSCLC) is controversial.</P>

Nanostructured Tendon-Derived Scaffolds for Enhanced Bone Regeneration by Human Adipose-Derived Stem Cells

Ko, Eunkyung,Alberti, Kyle,Lee, Jong Seung,Yang, Kisuk,Jin, Yoonhee,Shin, Jisoo,Yang, Hee Seok,Xu, Qiaobing,Cho, Seung-Woo American Chemical Society 2016 ACS APPLIED MATERIALS & INTERFACES Vol.8 No.35

<P>Decellularized matrix-based scaffolds can induce enhanced tissue regeneration due to their biochemical, biophysical, and mechanical similarity to native tissues. In this study, we report a nanostructured decellularized tendon scaffold with aligned, nanofibrous structures to enhance osteogenic differentiation and in vivo bone formation of human adipose-derived stem cells (hADSCs). Using a bioskiving method, we prepared decellularized tendon scaffolds from tissue slices of bovine Achilles and neck tendons with or without fixation, and investigated the effects on physical and mechanical properties of decellularized tendon scaffolds, based on the types and concentrations of cross linking agents. In general, we found that decellularized tendon scaffolds without fixative treatments were more effective in inducing osteogenic differentiation and mineralization of hADSCs in vitro. When non cross-linked decellularized tendon scaffolds were applied together with hydroxyapatite for hADSC transplantation in critical-sized bone defects, they promoted bone-specific collagen deposition and, mineralized bone formation 4 and 8 weeks after hADSC transplantation, compared to conventional collagen type I scaffolds. Interestingly, stacking of decellularized tendon scaffolds cultured with osteogenically committed hADSCs and those containing human cord blood-derived endothelial progenitor cells (hEPCs) induced vascularized bone regeneration in the defects 8 weeks after transplantation. Our study suggests that biomimetic nanostructured scaffolds made of decellularized tissue matrices can serve as functional tissue-engineering scaffolds for enhanced osteogenesis of stem cells.</P>

EXISTENCE OF POSITIVE SOLUTION FOR A SEMIPOSITONE SYSTEM WITH INTEGRAL BOUNDARY VALUES

Ko, Eunkyung,Lee, Eun Kyoung The Youngnam Mathematical Society 2020 East Asian mathematical journal Vol.36 No.5

We establish the existence of a positive solution to a semipositone system with integral boundary condition for the large value of the parameter involved in the system. We prove our results by using sub and super solution argument.

Promoter hypermethylation of the p16 gene is associated with poor prognosis in recurrent early-stage hepatocellular carcinoma.

Ko, Eunkyung,Kim, Yujin,Kim, Sung-Joo,Joh, Jae-Won,Song, SangYong,Park, Cheol-Keun,Park, Joobae,Kim, Duk-Hwan American Association for Cancer Research 2008 Cancer epidemiology, biomarkers & prevention Vol.17 No.9

<P>Despite significant advances in the detection and treatment of hepatocellular carcinoma, the prognosis of patients with hepatocellular carcinoma remains very poor, in part due to the high incidence of recurrence. This study was aimed at identifying a prognostic indicator of recurrence in patients with hepatocellular carcinoma. We retrospectively analyzed CpG island hypermethylation of the p14, p15, p16, GSTP1, integrin alpha4, SYK, and CDH1 genes in fresh-frozen tissues from 265 patients with hepatocellular carcinoma using the methylation-specific PCR. The expression levels of p16 and p53 were evaluated by immunohistochemistry. CpG island hypermethylation was detected in 6% for p14, 21% for p15, 67% for p16, 75% for GSTP1, 23% for integrin alpha4, 12% for SYK, and 57% for CDH1. Recurrence was observed in 102 (38%) of the 265 patients. There was no association between the risk for recurrence and hypermethylation of any gene studied. However, p16 methylation was associated with a poor survival after surgery for recurrent stage I to II hepatocellular carcinomas (hazard ratio, 4.05; 95% confidence interval, 1.15-14.20; P = 0.03). In addition, the hazard of failure after recurrence was about 3.80 (95% confidence interval, 1.03-14.20; P = 0.04) times higher in patients with p16 methylation than in those without. Negative expression of p16 at a protein level was also associated with poor survival in recurrent stage I to II hepatocellular carcinomas, but p53 expression did not have a synergistic effect on the poor prognosis. In conclusion, the present study suggests that p16 methylation may be associated with a poor prognosis in recurrent early-stage hepatocellular carcinomas.</P>

Cystatin M loss is associated with the losses of estrogen receptor, progesterone receptor, and HER4 in invasive breast cancer

Ko, Eunkyung,Park, Seong-Eun,Cho, Eun Yoon,Kim, Yujin,Hwang, Jung-Ah,Lee, Yeon-Su,Nam, Seok Jin,Bang, Saik,Park, Joobae,Kim, Duk-Hwan BioMed Central 2010 Breast cancer research Vol.12 No.6

<P><B>Introduction</B></P><P>This study was aimed at understanding the clinicopathological significance of cystatin M loss, and investigating possible factors responsible for cystatin M loss in breast cancer.</P><P><B>Methods</B></P><P>The expression of estrogen receptor (ER), progesterone receptor (PR), HER2, HER4, and cystatin M was retrospectively analyzed using immunohistochemistry in 117 patients with ductal carcinoma <I>in situ </I>(DCIS) and in 175 patients with invasive breast cancer (IBC). The methylation status of <I>CST6 </I>gene encoding cystatin M was evaluated using methylation-specific polymerase chain reaction (PCR) in formalin-fixed paraffin-embedded tissues from 292 participants and using pyrosequencing in fresh-frozen tumor and matched normal tissues from 51 IBC patients.</P><P><B>Results</B></P><P>Cystatin M loss was found in 9 (8%) of 117 patients with DCIS and in 99 (57%) of 175 with invasive breast cancer (IBC) (<I>P </I>< 0.0001). Cystatin M loss was found in 58 (57%) of 101 HER2-negative IBCs and in 41 (55%) of 74 HER2-positive IBCs, and this difference was not statistically significant (<I>P </I>= 0.97). However, cystatin M loss was significantly associated with the loss of ER (<I>P </I>= 0.01), PR (<I>P </I>= 0.002), and HER4 (<I>P </I>= 0.003) in IBCs. Cystatin M loss occurred in 34 (76%) of the 45 HER4-negative IBCs and in 65 (50%) of the 130 HER4-positive IBCs. Multivariate analysis showed that cystatin M loss occurred at a 3.57 times (95% CI = 1.28 to 9.98; <I>P </I>= 0.01) higher prevalence in the triple-negative IBCs of ER, PR, and HER4 than in other subtypes, after adjusting for age. The quantity of <I>CST6 </I>methylation was associated with ER loss (<I>P </I>= 0.0002) in IBCs but not with the loss of PR (<I>P </I>= 0.64) or HER4 (<I>P </I>= 0.87).</P><P><B>Conclusions</B></P><P>The present study suggests that cystatin M loss may be associated with the losses of ER, PR, and HER4 in IBC.</P>

Existence of multiple positive solutions to integral boundary value systems with boundary multiparameters

Ko, Eunkyung,Lee, Eun Kyoung Springer (Biomed Central Ltd.) 2018 Boundary value problems Vol.2018 No.1

Adhesion behavior of mouse liver cancer cells on nanostructured superhydrophobic and superhydrophilic surfaces

Ko, Tae-Jun,Kim, Eunkyung,Nagashima, So,Oh, Kyu Hwan,Lee, Kwang-Ryeol,Kim, Soyoun,Moon, Myoung-Woon The Royal Society of Chemistry 2013 Soft matter Vol.9 No.36

<P>The control of cancer cell adhesion behavior on certain surfaces has been widely studied in recent years to enhance cell adhesion, which is required for bio-sensing, implant biomaterials, or to prevent infections from bacteria or germs. In addition, it helps to preserve the original functions of medical devices such as implants, catheters, injection syringes, and vascular stents. In this study, we explored the behavior of mouse liver cancer cells on nanostructured surfaces in extreme wetting conditions of a superhydrophobic or superhydrophilic nature. Oxygen plasma treatment of polymeric surfaces induced the formation of nanostructures such as bumps or hairs with various aspect ratios, which is defined as the height to diameter ratio. A superhydrophobic surface with a contact angle (CA) of 161.1° was obtained through the hydrophobic coating of a nanostructured surface with a high aspect ratio of 25.8. On the other hand, an opposite extreme wetting surface with a superhydrophilic nature with a CA of 1.7° was obtained through the hydrophilic coating of the same structured surface. The mouse liver cancer cells significantly proliferated on a mild hydrophilic surface with a low aspect ratio nanostructure due to the mild roughness and improvements of mechanical anchoring. However, the superhydrophilic surface with a high aspect ratio nanostructure (<I>i.e.</I>, hair shaped) suppressed the growth of the cancer cells due to the limited number of sites for focal adhesion, which restricted the adhesion of cancer cells and resulted in a decrease in the cell-covered area. The superhydrophobic nanostructured surface with a high aspect ratio further restricted the adhesion and growth of the cancer cells; the cell activity was extremely suppressed and the spherical shape of the cancer cells was maintained. Thus, this simple method for fabricating nanostructured surfaces with various wetting conditions might be useful for producing biomedical devices such as stents, implants, drug delivery devices, and detection and/or sensing devices for cancer cells.</P> <P>Graphic Abstract</P><P>The cancer cell adhesion behavior on the superhydrophobic or superhydrophilic surfaces has been explored to enhance cell adhesion required for bio-sensing, implant, biomaterials, or to prevent infections from bacteria or germs. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c3sm51147b'> </P>

The Performance Test of Induction Type Furnace for the Design of Tritium Desorption System

Eunkyung Jung,Kyu Min Song,Byunwook Ko,Kahee Jeong,Seungchul Park 한국방사성폐기물학회 2017 한국방사성폐기물학회 학술논문요약집 Vol.2017 No.05