<b>Combined Sustained Delivery of Basic Fibroblast Growth Factor and Administration of Granulocyte Colony-Stimulating Factor:</b>Synergistic Effect on Angiogenesis in Mouse Ischemic Limbs

Jeon, Oju,Hwang, Ki-Chul,Yoo, Kyung-Jong,Kim, Byung-Soo International Society of Endovascular Specialists 2006 Journal of endovascular therapy Vol.13 No.2

<P>PURPOSE: To investigate whether the efficacy of a single angiogenic therapy (sustained delivery of basic fibroblast growth factor [bFGF] or administration of granulocyte colony-stimulating factor [G-CSF]) can be enhanced further by combining the therapies. METHODS: One day after surgical induction of hind-limb ischemia, groups of 6 mice were randomized to receive either no treatment, sustained delivery (SD) of bFGF, endothelial progenitor cell (EPC) mobilization with G-CSF administration, or a combination of bFGF SD + G-CSF administration. RESULTS: G-CSF administration increased significantly (p < 0.05) the number of EPC lineages (CD34 + /AC133 + cells) in both peripheral blood and bone marrow compared to no G-CSF administration. The bFGF SD and G-CSF administration individually increased the capillary and arteriole densities significantly versus no treatment (capillary density: 659 +/- 48/mm2 and 385 +/- 59/mm2, respectively, versus 280 +/- 28/mm2; p < 0.05; arteriole density: 34 +/- 9/mm2 and 41 +/- 6/mm2, respectively, versus 15 +/- 2/mm2; p<0.05). Importantly, bFGF SD + G-CSF further increased the capillary and arteriole densities compared to either strategy alone (capillary density: 786 +/- 40/mm2 versus 659 +/- 48/mm2 and 385 +/- 59/mm2, respectively, p < 0.05; arteriole density: 55 +/- 10/mm2 versus 34 +/- 9/mm2 and 41 +/- 6/mm2, respectively, p < 0.05). CONCLUSION: This study demonstrates that the combined therapy of sustained bFGF delivery and G-CSF administration potentiates the angiogenic efficacy of either single therapy in mouse hind-limb ischemia models.</P>

Controlled release of nerve growth factor from fibrin gel

Bhang, Suk Ho,Jeon, Oju,Choi, Cha Yong,Kwon, Yun Hee Kim,Kim, Byung‐,Soo Wiley Subscription Services, Inc., A Wiley Company 2007 Journal of biomedical materials research. Part A Vol.a80 No.4

<P><B>Abstract</B></P><P>Nerve growth factor (NGF) is known to promote the axonal regeneration in injured nerve system. Delivery of NGF for a long period in a controlled manner may enhance the regeneration efficacy. In this study, we investigated whether NGF can be released from fibrin gel for a long period in a controlled manner. We also investigated whether sustained delivery of NGF using fibrin gel can enhance the efficacy of NGF <I>in vitro</I>. The addition of heparin to fibrin gel decreased the rate of NGF release from the fibrin gel. As the concentrations of thrombin and fibrinogen in fibrin gel increased, the NGF release rate decreased significantly, and the initial release burst decreased. NGF was released for up to 14 days <I>in vitro</I>. The bioactivity of NGF released from fibrin gel was assessed by morphological changes of pheochromocytoma (PC12) cells cultured in the presence of NGF‐containing fibrin gel. NGF released from fibrin gel exhibited significantly higher degrees of PC12 cell viability and differentiation than NGF added in a free form daily into the culture medium. This study demonstrates that fibrin gel can release NGF in a sustained, controlled manner and in a bioactive form. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007</P>

Cell Detachment from Microcarriers without Trypsinization

Hee Seok Yang,Oju Jeon,Byung-Soo Kim 한국생물공학회 2008 한국생물공학회 학술대회 Vol.2008 No.4

Interconnectable Dynamic Compression Bioreactors for Combinatorial Screening of Cell Mechanobiology in Three Dimensions

Seo, Jungmok,Shin, Jung-Youn,Leijten, Jeroen,Jeon, Oju,Bal Ö,ztü,rk, Ayç,a,Rouwkema, Jeroen,Li, Yuancheng,Shin, Su Ryon,Hajiali, Hadi,Alsberg, Eben,Khademhosseini, Ali American Chemical Society 2018 ACS APPLIED MATERIALS & INTERFACES Vol.10 No.16

<P>Biophysical cues can potently direct a cell’s or tissue’s behavior. Cells interpret their biophysical surroundings, such as matrix stiffness or dynamic mechanical stimulation, through mechanotransduction. However, our understanding of the various aspects of mechanotransduction has been limited by the lack of proper analysis platforms capable of screening three-dimensional (3D) cellular behaviors in response to biophysical cues. Here, we developed a dynamic compression bioreactor to study the combinational effects of biomaterial composition and dynamic mechanical compression on cellular behavior in 3D hydrogels. The bioreactor contained multiple actuating posts that could apply cyclic compressive strains ranging from 0 to 42% to arrays of cell-encapsulated hydrogels. The bioreactor could be interconnected with other compressive bioreactors, which enabled the combinatorial screenings of 3D cellular behaviors simultaneously. As an application of the screening platform, cell spreading, and osteogenic differentiation of human mesenchymal stem cells (hMSCs) were characterized in 3D gelatin methacryloyl (GelMA) hydrogels. Increasing hydrogel concentration from 5 to 10% restricted the cell spreading, however, dynamic compressive strain increased cell spreading. Osteogenic differentiation of hMSCs was also affected by dynamic compressive strains. hMSCs in 5% GelMA hydrogel were more sensitive to strains, and the 42% strain group showed a significant increase in osteogenic differentiation compared to other groups. The interconnectable dynamic compression bioreactor provides an efficient way to study the interactions of cells and their physical microenvironments in three dimensions.</P> [FIG OMISSION]</BR>

자가 골수 중간엽줄기세포와 생분해성 고분자 스캐폴드를이용한 조직공학적 인공혈관 제조

조승우,김동익,박희정,임상현,전오주,김수현,김영하,최차용,이민재,김종성,장인성,김병수 대한혈관외과학회 2003 Vascular Specialist International Vol.19 No.2

Tissue-engineered blood vessels with endothelial nitric oxide synthase activity

Lim, Sang Hyun,Cho, Seung-Woo,Park, Jong-Chul,Jeon, Oju,Lim, Jae Min,Kim, Sang-Soo,Kim, Byung-Soo Wiley Subscription Services, Inc., A Wiley Company 2008 Journal of Biomedical Materials Research Part B Vol. No.

<P>Nondegradable synthetic polymer vascular grafts used in cardiovascular surgery have shown serious shortcomings, including thrombosis, calcification, infection, and lack of growth potential. Tissue engineering of vascular grafts with autologous stem cells and biodegradable polymeric materials could solve these problems. The present study is aimed to develop a tissue-engineered vascular graft (TEVG) with functional endothelium using autologous bone marrow-derived cells (BMCs) and a hybrid biodegradable polymer scaffold. Hybrid biodegradable polymer scaffolds were fabricated from poly(lactide-co-ϵ-caprolactone) (PLCL) copolymer reinforced with poly(glycolic acid) (PGA) fibers. Canine bone marrow mononuclear cells were induced in vitro to differentiate into vascular smooth muscle cells and endothelial cells. TEVGs (internal diameter: 10 mm, length: 40 mm) were fabricated by seeding vascular cells differentiated from BMCs onto PGA/PLCL scaffolds and implanted into the abdominal aorta of bone marrow donor dogs (n = 7). Eight weeks after implantation of the TEVGs, the vascular grafts remained patent. Histological and immunohistochemical analyses of the vascular grafts retrieved at 8 weeks revealed the regeneration of endothelium and smooth muscle and the presence of collagen. Western blot analysis showed that endothelial nitric oxide synthase (eNOS) was expressed in TEVGs comparable to native abdominal aortas. This study demonstrates that vascular grafts with significant eNOS activity can be tissue-engineered with autologous BMCs and hybrid biodegradable polymer scaffolds. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008</P>

섬유소 아교에 혼합된 골 형성 단백이 건-골 결합부 손상의 재생에 미치는 영향

김학준(Hak Jun Kim),박정호(Jung-Ho Park),임홍철(Hong-Chul Lim),김병수(Byung-Soo Kim),이재선(Jae-Sun Lee),강선웅(Sun-Woong Gang),전오주(Oju Jeon) 대한정형외과학회 2007 대한정형외과학회지 Vol.42 No.1

목적: 저자들은 건-골 결합부의 손상에 외부적으로 주입된 골형성 단백이 초기 재생 과정에서 건-골 결합력의 증대를 가져오는지에 대해 알아보고자 하였다. 대상 및 방법: 가토 54마리를 대상으로 하였으며 가토의 아킬레스 건-골 결합부에서 절제를 시행한 후 Kracow 술식을 이용하여 봉합한 세 군에서 Ⅰ군을 봉합 부위에 아무런 처치를 시행하지 않은 군으로, Ⅱ군은 섬유소아교만을 봉합 부위에 주입하였으며, Ⅲ군은 골형성 단백을 포함한 섬유소 아교를 주입하여 실험 2, 4, 8주에 각군의 조직학적 소견 및 생역학적 강도를 비교하여 골형성 단백-2의 효과를 알아보았다. 통계학적 검정은 Kruskal-Wallis test를 이용하였다. 결과: 조직학적 소견상 골형성 단백을 포함한 섬유소 아교를 주입한 Ⅲ군은 다른 군보다 실험 2주째부터 섬유 연골이 나타났으며 그 두께가 증가하였다. 생 역학적 결과에서는 Ⅲ군은 Ⅰ군과 Ⅱ군보다 실험 2주째부터 최대 인장 강도에서 통계학적으로 의미 있는 증가를 보였고, 실험 8주째에서는 Ⅲ군의 평균 최대 인장 강도가 정상 아킬레스 건-골 결합부의 인장 강도의 74.7%까지 회복되었다. 결론: 골형성 단백-2를 포함한 섬유소 아교의 주입은 건-골 결합부 손상의 재생을 촉진시킬 수 있을 것이다. Purpose: The author hypothesizes that exogenously injected BMP, which is mixed with fibrin glue, can accelerate the healing of a bone-tendon junction injury and increase its holding strength during the early regeneration period. Materials and Methods: A direct injury model of the bone-tendon junction was made using the Achilles tendon-calcaneus bone of 54 rabbits: and the transected Achilles tendon was repaired to its original insertion site using the Krackow method. In Group 1, no additional manipulation was performed. In Group 2, only fibrin glue was injected into the junction between the Achilles tendon and the calcaneus in order to exclude the effect of the fibrin glue. In Group 3, BMP-2 incorporated into the fibrin glue was injected into the junction. The results were evaluated by histological analysis and biomechanical tests at 2, 4, and 8 weeks after surgery. The Kruskal-Wallis test was used for a statistical evaluation. Results: Histological analysis revealed the early appearance of fibrocartilage at 2 weeks in Group 3: the area of the fibrocartilage expanded with time. The biomechanical tests showed significant differences in the maximum stress between Groups 1 and 3, and between Groups 2 and 3, at 2, 4, and 8 weeks. 74.4% of the normal maximum stress was recovered at 8 weeks in Group 3. Conclusion: The combined use of BMP-2 and the fibrin glue can accelerate the healing of an injury of the bone-tendon junction.