• Biomaterials and Biomechanics in Bioengineering
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• 제1권1호
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• pp.27-39
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• 2014

We have previously described a new multilayer alginate microcapsule system, and the goals of the present study were to assess the in vitro function of islets encapsulated in its inner layer, and the angiogenic ability of FGF-1 delivered from the external layer in an omentum pouch. Following isolation and culture, islets were encapsulated in the inner core of microspheres ($500-600{\mu}m$ in diameter) with a semi-permeable poly-L-ornithine (PLO) membrane separating two alginate layers, and both unencapsulated and encapsulated islet function was assessed by a dynamic glucose perifusion. For angiogenesis experiments, one group of microcapsules without FGF-1 (control) and another (test) containing FGF-1 with heparin encapsulated in the external layer were made. One hundred microcapsules of each group were transplanted in Lewis rats (n = 5/group) and were retrieved after 14 days for assessment of angiogenesis. Glucose perifusion of unencapsulated and encapsulated islets resulted in similar stimulation indices. The release of FGF-1 resulted in increased vascular density compared to controls. In conclusion, islets encapsulated in the core of multilayer alginate microcapsules maintain functionality and the microcapsule's external layer is effective in delivery of FGF-1 to enhance graft neovascularization in a retrievable omentum pouch.

• Archives of Plastic Surgery
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• 제43권6호
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• pp.491-497
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• 2016

Background Hypertrophic scarring is a pathological condition that occurs after trauma or surgery. Angiogenesis occurs more often with hypertrophic scarring than with normotrophic scarring. The regulation of angiogenesis is one of the key factors in hypertrophic scar management. Vascular endothelial growth factor (VEGF) is an essential factor in the angiogenetic response. This study investigated whether decreasing the level of VEGF is effective for treating hypertrophic scarring. Methods Ten 8-week-old female New Zealand white rabbits were included. Four defects were created on each ear by using a 6-mm punch. Bevacizumab (Avastin, Roche Pharma, Basel, Switzerland) was administered in one ear and normal saline was administered in the other ear. Treatment was administered starting on day 2, every 2 days, until day 14. The levels of VEGF were measured using enzyme-linked immunosorbent assay on day 10 and histologic results were analyzed on day 40. Results Bevacizumab induced-defects showed less hypertrophic scarring when compared with the control group as measured by the scar elevation index (SEI) and loose collagen arrangement. The SEI in the experimental group was $1.89{\pm}0.13$, compared to $1.99{\pm}0.13$ in the control group (n=30, P=0.005). Additionally, the VEGF level was lower ($38.72{\pm}11.03pg$ vs. $82.50{\pm}21.64pg$, n=10, P=0.001) and fewer vessels existed ($8.58{\pm}0.76$ vs. $7.2{\pm}1.20$, n=10, P=0.007). Conclusions Preventing excessive angiogenesis is effective for preventing scar formation, especially with hypertrophic scarring. Although it is not an approach that is sufficient alone for the management of scarring, it may be one of several important strategies for scar treatment.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제18권2호
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• pp.269-278
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• 1996

To overcome the limitations of conventional microsurgical tissue transfer, experimental creation of various neo-flaps using the vessel implantation technique has been reported. We have performed some experiments of fabrication of neo-osseous flap with local vessels and iliac bone slabs to know that the flap vascularity and neo-angiogenesis are achieved enough to microtransfer. As a next step of our previous experiments, the flap viability and the histologic change between the recipient bone and neo-oseous flap was assessed after microsurgical transplantation. The flap was created on the rabbit femoral region(n=25) using femoral vessel and the iliac bone segments($2.5{\times}1.5cm$ in size). Three weeks after neovascularization, the newly formed flap was harvested and microtransferred to the mandibular defect. As a control, contralateral mandibular defect was created and reconstructed with conventional free iliac bone graft. Scintigrams of experimental group performed 3 days after microtransfer showed hot uptake, while that of control poor uptake. Histologic and vital stain labeling study revealed good bone viability and vascularity of neo-osseous flap. In conclusion, prefabricated neo-osseous flap of our model could be transferred to the recipient site with retaining the flap viability and showed advantages over the conventional bone graft in that it was living bone graft.

• Archives of Plastic Surgery
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• 제36권3호
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• pp.254-261
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• 2009

Purpose: The objective of this study was to evaluate the heparin effect for a viability of random - pattern dorsal flap in hairless mouse. Methods: A caudally - based random dorsal flap, measuring $1.5{\times}5cm$, was designed and heparin was applied topically after microneeding. Twenty five male hairless mice were randomly divided into control (Group1, n=5); received only microneedling (Group 2, n=5), only heparin(Group3, n=5), microneedling with saline(Group 4, n=5), and microneedling with heparin group(group5,n=5) to the flap during 7 days. The number of the capillaries were compared between the experimental groups and control group with respect to neovascularization after heparin application using imaging analysis program under hematoxylin - eosin stain. The capillary blood flow was measured by laser Doppler flowmetry. After seven days each animal was evaluated for the percentage area of the flap survival. Mann - Whitnety U test and Kruskal - Wallis statistical analysis of survival relationships was performed. Results: It can be observed increased number of the blood vessels in the experimental groups however it was not statistically significant. Blood flow of the haparin with microneedling group maintained higher than other experimental groups. Treated microneeding and heparin mice were significantly better flap viability than in controls (flap survival 67% and $54.4mm^2$ respectively; p<.01). Positive correlation was shown between flap survival rate and laser Doppler flux value only at first day after surgery. Conclusion: Heparin has a beneficial effect on capillary flow and improve peripheral circulatory disturbances in random pattern flaps.

• Biomolecules & Therapeutics
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• 제23권6호
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• pp.517-524
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• 2015

Human mesenchymal stem cells (MSCs) have been used in cell-based therapy to promote revascularization after peripheral or myocardial ischemia. High levels of reactive oxygen species (ROS) are involved in the senescence and apoptosis of MSCs, causing defective neovascularization. Here, we examined the effect of the natural antioxidant lycopene on oxidative stress-induced apoptosis in MSCs. Although $H_2O_2$ ($200{\mu}M$) increased intracellular ROS levels in human MSCs, lycopene ($10{\mu}M$) pretreatment suppressed $H_2O_2$-induced ROS generation and increased survival. $H_2O_2$-induced ROS increased the levels of phosphorylated p38 mitogen activated protein kinase (MAPK), Jun-N-terminal kinase (JNK), ataxia telangiectasia mutated (ATM), and p53, which were inhibited by lycopene pretreatment. Furthermore, lycopene pretreatment decreased the expression of cleaved poly (ADP ribose) polymerase-1 (PARP-1) and caspase-3 and increased the expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax), which were induced by $H_2O_2$ treatment. Moreover, lycopene significantly increased manganese superoxide dismutase (MnSOD) expression and decreased cellular ROS levels via the PI3K-Akt pathway. Our findings show that lycopene pretreatment prevents ischemic injury by suppressing apoptosis-associated signal pathway and enhancing anti-oxidant protein, suggesting that lycopene could be developed as a beneficial broad-spectrum agent for the successful MSC transplantation in ischemic diseases.

• 대한한방내과학회지
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• 제22권4호
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• pp.639-645
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• 2001

Angiogenesis is a fundamental process in reproduction and wound healing. Under these condition, neovascularization is tightly regulated. Unregulated angiogenesis may lead to several angiogenic diseases, and is thought to be indispensible for solid tumor growth and metastsis. The construction of new vascular network is a multistep cascade involving basement membrane degradation, endothelial cell proliferation, endothelial cell migration, and tube formation. Newly reported anti-angiogenic agents in oriental medical field have targeted both specific and multistep stages in the angiogenic process. From recent approach in oriental medical field with several herb medicines including activating blood flow and removing blood stasis medicine(活血化瘀藥), it may be possible in the future to develope specific anti-angiogenic agents that offer a less toxic potential therapy for cancer and angiogenic disease.

• Archives of Plastic Surgery
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• 제33권5호
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• pp.592-600
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• 2006

Purpose: Numerous materials, both autologous and nonautologous, have been used for augmentation of sunken areas, but they have their own limitations. The purpose of this study is to determine the histologic response and volume change of the xenogenic collagen-based scaffold($Terudermis^{(R)}$) to the transfer into a subcutaneous soft tissue location in vivo rabbit model. Methods: Eighteen New Zealand white rabbits were used. Three $1.2{\times}1.2cm$ sized subcutaneous pockets were created on the dorsal surface of each ear. $1{\times}1cm$ sized collagen matrix($Terudermis^{(R)}$) and autologous dermal graft were implanted into each pocket. Full thickness of ear was harvested in 3 days, 1, 2, 4 weeks, 3, 6 months after implantation. Results: Histological analysis of implants demonstrated progressive neovascularization, fibroblast infilteration, neocollagen bundle synthesis and organization, and few foreign body reaction. The thickness of the collagen matrix in 3 days after the operation was 87.69% of the thickness of the collagen matrix in wet state. Then it decreased to 30.17% in 6 months after the operation. The rate of decrease was similar at all points at the same time compared with autologous dermal graft. Conclusion: Our experimental study suggests that $Terudermis^{(R)}$ could be a safe material as an implant for permanent augmentation in subcutaneous tissue. However the choice of graft for augmentation should be remained to the clinical situations.

• Archives of Plastic Surgery
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• 제33권5호
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• pp.621-626
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• 2006

Purpose: Erythropoietin is traditionally known to regulate erythropoiesis, but recently its protective effect against ischemia-reperfusion injury has been studied mainly in cardiovascular and neuronal systems. This study was planned to investigate the effects of recombinant human erythropoietin on ischemia-reperfusion injury in rat TRAM flap model. Methods: Superiorly based TRAM flap was elevated and ischemic insult was given for four hours. Thirty minutes before reperfusion, single dose recombinant human Erythropoietin(5000IU/kg) was injected via intraperitoneal route in the treatment group. At 24 hours postoperatively, systemic neutrophil count, tissue myeloperoxidase activity, malonyldialdehyde amount, nitric oxide content, tissue water content and histologic finding of inflammation was evaluated. On 10 days postoperatively, flap survival rate, angiogenesis and change in hematocrit level was evaluated. Results: Tissue nitric oxide level was significantly higher and myeloperoxidase activity was significantly lower in the treatment group 24 hours after reperfusion. Tissue water content was significantly lower in the treatment group. Perivascular neutrophil infiltration and intravascular adhesion was marked in the control group. Mean flap survival after ten days was 69% in the treatment group, and 47% in the control group, demonstrating a significant difference. Neovascularization in the treatment group also outnumbered the control group. No significant hematocrit rise was noted ten days after erythropoietin administration. Conclusion: Recombinant human Erythropoietin improved flap survival in ischemia-reperfusion injured rat TRAM flaps, at least partially owing to suppressed inflammation, increased nitric oxide, and enhanced angiogenesis.

• Journal of Korean Neurosurgical Society
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• 제29권10호
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• pp.1303-1308
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• 2000

Objectives : It has been known that vascular endothelial growth factor(VEGF), as an endothelial cell-specific mitogen, induces angiogenesis, and possesses vascular permeability and procoagulant properties. Peritumoral brain edema(PTBE) is a common accompaniment of malignant gliomas. It results from microvascular extravasation of plasma and proteins through the interendothelial spaces. The correlation between pathological grading, PTBE, neovascularization, and the expression of VEGF were analyzed in 31 patients with astrocytic tumors. Methods : Astrocytic tumor samples(8 astrocytomas, 14 anaplastic astrocytomas, and 9 glioblastomas) from 31 patients( 21 males and 10 females : average age $37{\pm}24$ years) who underwent surgery were examined retrospectively for the expression of VEGF and CD31(microvasculature) immunohistochemically. The extent of PTBE was examined by using preoperative CT or MRI as an edema index(EI). In addition to VEGF and CD31, several causative factors including tumor size, histologic type were compared with EI. Results : Only one of 8 astrocytomas, and majority of high grade(21 of 23 anaplastic astrocytomas and glioblastomas) tumors demonstrated PTBE(p<0.05). The majority of high grade tumors showed higher expression of VEGF (p<0.01). High grade tumors showed even higher CD31 expression(p<0.05), however, there was no close correlation between expression of VEGF and CD31. The EI was increased significantly, just as VEGF(p<0.01), but CD31 expression was not correlated with high EI. Conclusion : These data suggest that VEGF expression is closely correlated with PTBE and histological grading in astrocytic tumors. Microvasculature(CD31) in tumors is highly correlated with histological grading, however, shows no correlation with the expression of VEGF and PTBE.

• 한국임상수의학회지
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• 제28권1호
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• pp.28-32
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• 2011

This study was performed to evaluate the efficacy of 0.8% sodium hyaluronic acid solution and crosslinked hyaluronic acid mixture for the prevention of postoperative intraperitoneal adhesion in rats. Forty-five animals were divided into three groups ; 0.9% saline treated control group, 1% sodium carboxymethyl cellulose treated group (SCMC), and 0.8% sodium hyaluronic acid solution and crosslinked hyaluronic acid mixture treated group (SHCH). Adhesions were induced by suturing both the ileal serosa and peritoneum abrased until petechial bleeding occurred. Fourteen days later, adhesions were evaluated clinically and histopathologically. The mean tensile strength was significantly decreased in the SCMC and SHCH groups compared to the control group (p < 0.05), and the SHCH group had the lowest tensile strength. The distance of adhesion site was highest in the control group and significantly decreased in the SHCH group comparing control group (p < 0.05). The inflammatory cell infiltration, collagen hyperplasia and neovascularization of the SCMC and SHCH groups were significantly lower than the control group (p < 0.05). Therefore, it was concluded that the SHCH may be useful to prevent postoperative intraperitoneal adhesion in rats.