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박용두,Park, Yong-Doo 대한의용생체공학회 2010 의공학회지 Vol.31 No.2
Researches for stem cells have been focused on scientists in biomedical sciences as well as clinical application for its great therapeutic potentials. Stem cells have two distinct characteristics: self-renewal and differentiation. In this short review, the links between stem cell research and biomedical engineering is discussed based on the basic characteristics of stem cells. This concept can be extended to the fundamental questions of biological sciences for cells such as proliferation, apoptosis, differentiation, and migration. For understanding proliferation and apoptosis of stem cells, techniques from biomedical engineering such as surface patterning, MEMS, nanotechnologies have been used. The advanced technologies such as microfluidic technologies, three dimensional scaffold fabrication, and mechanical/electrical stimulation have also been used in cell differentiation and migration. Basic and unsolved questions in the stem cell research field have limitations by studying conventional technologies. Therefore, the strategic fusion between stem cell biology and novel biomedical engineering field will break the barriers for understanding fundamental questions of stem cells, which can open the window for the clinical applications of stem cell based therapeutics as well as regeneration of damaged tissues.
수직력하에서 임프란트 나사형태에 따른 응력의 3차원 유한요소법적 분석
김우택,차용두,오세종,박상수,김현우,박양호,박준우,이건주,Kim, Woo-Taek,Cha, Yong-Doo,Oh, Se-Jong,Park, Sang-Soo,Kim, Hyun-Woo,Park, Yang-Ho,Park, Jun-Woo,Rhee, Gun-Joo 대한구강악안면외과학회 2001 대한구강악안면외과학회지 Vol.27 No.2
There are three designs of thread form in screw type implants: V-thread, Reverse buttress thread and Square thread. The purpose of this study was to find out how thread form designs have an influence on the equivalent stress, equivalent strain, maximum shear stress and maximum shear strain and which design of thread form generates more maximum equivalent stress and strain. 3-D finite element analysis was used to evaluate the stress and strain patterns of three tread types. The results of this study were as follow. 1. Under the 200N of axial load, the value of maximum equivalent stress is smallest in square thread and there is no significant difference between that of V thread and reverse buttress thread. 2. Under the 200N of axial load, the value of maximum equivalent strain is largest in V thread and smallest in square thread. 3. Under the 200N of axial load, the value of maximum shear stress is smallest in square thread and there is no significant difference between that of V thread and reverse buttress thread. 4. Under the 200N of axial load, the value of maximum equivalent strain is largest in V thread and there is no significant difference between that of square thread and reverse buttress thread. 5. Above results show that the square thread has special advantages in stress and strain compared with other thread types, especially in shear stess which is most determinant to implant-bone interface. Considering the superior biomechanical properties of square form implant, we presume that square form implant has better clinical results than the other types of implants in the same clinical conditions.
세포외기질 단백질로 미세패턴화된 표면에서 성체 간엽 줄기세포의 형태변화와 세포점착차이에 관한 연구
김지연 ( Ji Youn Kim ),박용두 ( Yong Doo Park ),박정호 ( Jung Ho James Pak ),이규백 ( Kyu Back Lee ),선경 ( Kyung Sun ) 한국조직공학과 재생의학회 2004 조직공학과 재생의학 Vol.1 No.2
Patterning of surface using soft lithography is useful tools for regulating cellular morphology as well as function. Microcontact printing technology was used for patterning extracellular matrix (ECM) protein in this study. This pattern was used for controlling cellular adhesion as well as morphology of human mesenchymal stem cell. Polydimethylsiloxane (PDMS) molds was designed for controlling cellular adhesion by varying stripe width from 5 to 50 μm and fixing spacer to 20 μm. Glass surface was coated with extracellular matrix proteins such as fibronectin and vitronectin with different PDMS molds. Human mesenchymal stem cells were cultured on the patterned surfaces. Cells were aligned on the surfaces by changing cellular morphology. Actin filaments were aligned according to the protein stripe on the surfaces. The length of the actin fiber is longer as the stripe width is thinner. Proteins for focal contact such as vinculin, paxillin, and FAK were localized only on the ECM patterned surfaces. Especially, paxillin and FAK playing key role for focal adhesion were colocalized on the patterned surfaces. This study provides the controlling localization of focal adhesion proteins as well as morphology of human MSCs on the patterned surfaces. For further study, the effects of the localization of focal contacts proteins of MSCs to the stemness and differentiation will be investigated.
쥐의 골수로부터 추출한 줄기세포를 이용한 조골세포로의 분화 유도과정에서 나타난 문제점에 관한 분석 연구
김인숙,조태형,장옥련,이규백,박용두,노인섭,이종호,김명진,황순정,Kim, In-Sook,Cho, Tae-Hyung,Zhang, Yu-Lian,Lee, Kyu-Back,Park, Yong-Doo,Rho, In-Sub,Weber, F.,Lee, Jong-Ho,Kim, Myung-Jin,Hwang, Soon-Jung 대한악안면성형재건외과학회 2005 Maxillofacial Plastic Reconstructive Surgery Vol.27 No.1
This study was aimed to characterize osteogenic potential of rat bone marrow stromal cells (BMSC) isolated with standard flushing method and investigate the plasticity of transdifferentiation between osteoblastic and adipocytic lineage of cultured BMSC. Unlike aspiration method in human, rat bone marrow was extracted by means of irrigation with culture media that elevates the possibility of co-extraction of committed osteoprogenitor, or preosteoblast or other progenitor cells of several types present inside bone marrow. The cultured stromal cells showed high ALP activity which is representative marker of osteoblast without any treatment. Osteogenic inducers such as Dex and BMP-2 were examined for the evaluation of their effect on osteogenic and adipocytic differentiation of stromal cells, because they function as osteoinductive agent in stromal cells, but simultaneously induce adipogenic differentiation. Osteogenic differentiation was evaluated by measuring alkaline phosphatase activity or mRNA expression of osteoblast markers such as osteopontin, bone sialoprotein, collagen type I and CbfaI, and in vitro matrix mineralization by von Kossa staining. Oil red staining method was used to detect adipocyte and adipocytic marker, aP2 and $PPAR{\gamma}2$ expression was examined using RT-PCR. It can be supposed that irrigation procedure resulted in high portion of already differentiation-committed osteoprogenitor cell showing elevated ALP activity and strong mineralization only under the supplement of $100{\mu}M$ ascorbic 2-phosphate and 10mM ${\beta}$-glycerophosphate without any treatment of osteogenic inducers such as Dex and BMP-2. Dex and BMP-2 seemed to transdifferentiate osteoprogenitor cells having high ALP activity into adipocytes temporarily, but continuous treatment redifferentiated into osteoblast and developed in vitro matrix mineralization. This property must be considered either in tissue engineering for bone regeneration, or in research of characterization of osteogenic differentiation, with rat BMSC isolated by the standard irrigation method.
사람의 골수 줄기 세포로부터의 골세포 분화 과정에서 BMP-2가 미치는 영향과 그에 따른 분화 유전자의 발현 비교 연구
김인숙,장옥련,조태형,이규백,박용두,노인섭,황순정,김명진,이종호,Kim, In-Sook,Zhang, Yu-Lian,Cho, Tae-Hyung,Lee, Kyu-Back,Park, Yong-Doo,Rho, In-Sub,Weber, F.,Hwang, Soon-Jung,Kim, Myung-Jin,Lee, Jong-Ho 대한악안면성형재건외과학회 2005 Maxillofacial Plastic Reconstructive Surgery Vol.27 No.1
It is commonly acknowledged that bone morphogenic protein (BMP-2) functions as a potential osteogenic inducer in bone formation. Recently, several papers reported that bone marrow-derived stem cell (BMSC) from human is not responsive to BMP-2 in comparison to high capacity of BMP-2 in the osteoinduction of stromal cell derived from bone marrow of rodent animals such as rat or mouse. In this study, we characterized BMSC derived from 11 years old donor for the responsiveness to rhBMP-2, dexamethasone (Dex) and 1,25-dihydroxyvitamin D (vitamin D), in order to analyze their function in the early osteogenesis. The effect of over mentioned agents was evaluated by means of assessing alkaline phosphatase (ALP) activity/staining, RT-PCR analysis and von Kossa staining. In addition, we analyzed the meaning of expressed several osteoblastic markers such as alkaline phosphatase, collagen typeI, osteopontin, bone sialoprotein and osteocalcin with relation to either differentiation or mineralization. Only in the presence of Dex, human BMSC could commit osteoblastic differentiation and matrix mineralization, and either BMP-2 or vitamin D treatment was not able to induce. But BMP-2 or Vitamin D showed potential synergy effect with Dex. ALP and bone sialoprotein were clearly expressed in response of Dex treatment compared to weak expression of osteopontin in early osteogenesis. Therefore, we expect that this study will contribute partly to elucidiating early osteogenesis mechanism in human, but variations among bone marrow donors must be considered through further study.
남정훈(Jeong Hun Nam),박종철(Jong Chul Park),유상배(Sang Bae Yu),정용일(Yong Il Chung),태기융(Gi Yoong Tae),김정주(Jung Ju Kim),박용두(Yong Doo Park),장정원(Jeong Won Jahng),이종호(Jong Ho Lee) 대한구강악안면외과학회 2009 대한구강악안면외과학회지 Vol.35 No.3
As an efficient controlled release system for rhBMP-2, a functional nanoparticle-hydrogel complex, incorporated with matrix metalloproteinase(MMP) sensitive peptide cross-linker, was developed and used as a bone transplant. In vivo bone formation was evaluated by soft x-ray, histology, alkaline phosphatase(ALP) activity and mineral contents analysis, based on the rat calvarial critical size defect(8mm in diameter) model. Significantly, effective bone regeneration was achieved with the rhBMP-2 loaded MMP sensitive hyaluronic acid(HA) based hydrogel-Nanoparticles(NP) complex, as compared to only MMP HA, the MMP HA-NP without rhBMP-2, or even with the rhBMP-2. These improvements included the formation pattern of bone and functional marrow, the degree of calcium quantification, and the ALP activity. These results indicate that the MMP sensitive HA with nano-particle complex can be a promising candidate for a new bone defect replacement matrix, and an enhanced rhBMP-2 scaffold.
하이아루론산을 기재로 한 하이드로젤-나노입자 복합체와 rhBMP-2를 이용한 골재생
이종호 ( Jong Ho Lee ),김성민 ( Soung Min Kim ),박종철 ( Jong Chul Park ),성미애 ( Mi Ae Sung ),유상배 ( Sang Bae Yu ),남정훈 ( Jeong Hun Nam ),정용일 ( Yong Il Chung ),김정주 ( Jung Ju Kim ),박용두 ( Yong Doo Park ),태기융 ( Gi Y 한국조직공학·재생의학회 2009 조직공학과 재생의학 Vol.6 No.4
As an efficient controlled release system of rhBMP-2, a functional nanoparticle-130 KDa 5% Hyaluronic Acid (HA) based hydrogel-Nanoparticle(NP) complex was developed and used as a bone transplant. In vivo bone formation was evaluated by soft x-ray, histology, alkaline phosphatase (ALP)/Osteocalcin activity and mineral contents analysis, based on the rat calvarial critical size defect (8 mm in diameter) model. Significantly, effective bone regeneration was achieved with the rhBMP-2 loaded HA based hydrogel-NP complex and the BMP-2 loaded HA based hydrogel as compared to only HA hydrogel group with the period of 4 weeks. These improved results included areas such as radiodensity, the bone specific ALP activity, the osteocalcin immunoreactivity, and the ratio of calcium and phosphate contents with respect to normal bone in the regenerated bone area. Although superiority of bone regenration in the rhBMP-2 loaded HA based hydrogel-NP complex group could not be confirmed statistically, all the evaluation parameters were higher in the rhBMP-2 loaded HA based hydrogel-NP complex group than in the the BMP-2 loaded HA based hydrogel group. These results indicate that the HA based hydrogel with nanoparticle complex can be a promising candidate for a new bone defect replacement matrix, and an enhanced BMP-2 scaffold.
Streptomyces coelicolor의 연속 배양시 산소 분압에 따른 방어 효소의 활성 변화
박용두,이계준,노정혜 한국산업미생물학회 1994 한국미생물·생명공학회지 Vol.22 No.5
S. coelicolor 야생형과 과산화수소에 저항성을 보이는 돌연변이체 N7을 연속 배양하면서 산소 유입량을 변화시켜 산소량 변화에 따른 생리적 변화를 관찰하였다. 각 조건에서 세포량을 측정한 결과, 야생형은 공기 1.5 vvm까지는 공기 유입량에 의해 성장이 촉진되나 산소 0.5 vvm 이상에서는 성장이 저해됨이 관찰되었고, 돌연변이체는 산소 0.5 vvm까지 성장이 촉진되나 산소 1.0 vvm 이상의 조건에서는 산화적 스트레스를 받는 것으로 나타났다. 따라서 과산화수소에 저항성을 보이는 돌연변이체는 산소 분압을 변화시켜 스트레스를 주어도 야생형에 비해 보다 큰 저항성을 보인다는 것을 알았다. 산화적 스트레스에 대한 방어 효소의 활성을 측정한 결과 야생형은 catalase와 G6PDH의 활성이 산소 유입량의 증가에 따라 현저히 높아짐을 알 수 있었다. 그러나 돌연변이체는 방어 효소들의 활성이 야생형보다 약간 높으나 산소 유입량의 증가에 따라 증가하지 않는 항상적 발현 양상을 보이는 것으로 나타났다. S. coelicolor의 주된 catalase의 발현 양과 산소 분압의 연관성을 알아보기 위해 Western blotting을 한 결과 주된 catalase(Cat 3-2)의 단백질의 생산량과 전체 효소 활성이 비례함을 알 수 있었다. 따라서 산소 분압에 따른 catalase 활성의 증가는 거의 전적으로 주된 catalase(Cat 3-2)의 유도에 의한 것임을 확인하였다. Effect of partial oxygen pressure on the cell growth and the activities of oxidative defense enzymes were measured in the continuous culture of Streptomyces coelicolor. Both the wild type and the mutant strain resistant to hydrogen peroxide were cultured and the dry cell weight of the two cultures were measured at different oxygen tensions. Growth of the wild type was inhibited by oxygen at above 0.5 vvm. Growth of the hydrogen peroxide resistant mutant was stimulated by pure oxygen at 0.5 vvm but was inhibited by oxygen at 1.0 vvm. Therefore, growth of the hydrogen peroxide resistant mutant was less affected by the deleterious oxidative stress of oxygen. Activities of the several defense enzymes were also measured at different oxygen tensions. Activities of catalase and glucose-6-phosphate dehydrogenase increased significantly as oxygen pressure increased in the wild type culture. In the mutant, however, increase in those enzyme activities was not obvious whereas the uninduced levels of the above enzymes were higher than those of wild type. As judged by Western blotting, the amount of the major catalase increased as the oxygen pressure increased. This indicates that the induction of the catalase activity by oxygen pressure is mostly due to the increase in the expression level for the major catalase.