Coronary artery disease is a loading cause of morbidity and mortality across the world. Percutaneous coronary intervention has become the major technique of revascularization. However, restenosis remains a major limitation of this procedure. Recently the need for repeat intervention due to restenosis, the most vexing long-term failure of percutaneous coronary intervention, has been significantly reduced owing to the introduction of two major advances, intracoronary brachytherapy and the drug-eluting stents. Intracoronary brachytherapy has been employed in recent years to prevent restenosis lesions with effective results, principally in in-stent restenosis. Restenosis is generally considered as au excessive form of normal wound healing divided up in precesses: elastic recoil, neointimal hyperplasia, and negative vascular remodeling. Restenosis has previously been regarded as a proliferative process in which neointimal thickening, mediated by a cascade of inflammatory mediators and other factors, is the key factor. Ionizing radiation has been shown to decrease the proliferative response to injury in animal models of restenosis. Subsequently, several randomized, double blind trials have demonstrated that intracoronary brachytherapy can reduce the rates of both angiographic restenosis and clinical event rates in patients undergoing percutaneous coronary intervention for in stent restenosis. Some problems, such as late thrombosis and edge restenosis, have been identified as limiting factors of this technique. Brachytherapy is a promising method of preventing and treating coronary artery restenosis.
Background Locoregional stem cell delivery is very important for increasing the efficiency of cell therapy. Amnisite BA (Amnisite) is a freeze-dried amniotic membrane harvested from bovine placenta. The objective of this study was to investigate the retention of cells of the stromal vascular fraction (SVF) on Amnisite and to determine the effects of cell-loaded Amnisite in a porcine radiation-induced chronic wound model. Methods Initially, experiments were conducted to find the most suitable hydration and incubation conditions for the attachment of SVF cells extracted from pig fat to Amnisite. Before seeding, SVFs were labeled with PKH67. The SVF cell-loaded Amnisite (group S), Amnisite only (group A), and polyurethane foam (group C) were applied to treat radiation-induced chronic wounds in a porcine model. Biopsy was performed at 10, 14, and 21 days post-operation for histological analysis. Results Retaining the SVF on Amnisite required 30 minutes for hydration and 1 hour for incubation. A PKH67 fluorescence study showed that Amnisite successfully delivered the SVF to the wounds. In histological analysis, group S showed increased re-epithelialization and revascularization with decreased inflammation at 10 days post-operation. Conclusions SVFs had acceptable adherence on hydrated Amnisite, with successful cell delivery to a radiation-induced chronic wound model.
Choi, Sung Yoon;Kim, Byung Hwi;Huh, Beom Kang;Jeong, Woong;Park, Min;Park, Hyo Jin;Park, Ji-Ho;Heo, Chan Yeong;Choy, Young Bin
Journal of Industrial and Engineering Chemistry
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v.67
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pp.469-477
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2018
We describe surgical sutures enabled with the local, sustained delivery of a TGF-${\beta}$ inhibitory drug, tranilast. To fabricate drug-delivery sutures, we separately prepared a tranilast-loaded strand using poly (lactic-co-glycolic acid), which was then physically braided with a surgical suture already in clinical use. By this method, the drug-delivery sutures maintained the mechanical strength and allowed the modulation of drug release profiles by simply altering the tranilast-loaded strand. The drug-delivery sutures herein released tranilast for up to 14 days. When applied to animal models, scarring was indeed reduced with diminished TGF-${\beta}$ expression and fibroblast numbers during the entire 21 day testing period.
Yu, Shin-Hye;Kim, Soomin;Kim, Yujin;Lee, Seo-Eun;Park, Jong Hyeok;Cho, Gayoung;Ha, Jong-Cheon;Jung, Hahnsun;Lim, Sang-Min;Han, Kyuboem;Lee, Hong Kyu;Kang, Young Cheol;Kim, Chun-Hyung
BMB Reports
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v.55
no.3
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pp.136-141
/
2022
Inflammation is one of the body's natural responses to injury and illness as part of the healing process. However, persistent inflammation can lead to chronic inflammatory diseases and multi-organ failure. Altered mitochondrial function has been implicated in several acute and chronic inflammatory diseases by inducing an abnormal inflammatory response. Therefore, treating inflammatory diseases by recovering mitochondrial function may be a potential therapeutic approach. Recently, mitochondrial transplantation has been proven to be beneficial in hyperinflammatory animal models. However, it is unclear how mitochondrial transplantation attenuates inflammatory responses induced by external stimuli. Here, we isolated mitochondria from umbilical cord-derived mesenchymal stem cells, referred as to PN-101. We found that PN-101 could significantly reduce LPS-induced mortality in mice. In addition, in phorbol 12-myristate 13-acetate (PMA)-treated THP-1 macrophages, PN-101 attenuated LPS-induced increase production of pro-inflammatory cytokines. Furthermore, the anti-inflammatory effect of PN-101 was mediated by blockade of phosphorylation, nuclear translocation, and trans-activity of NFκB. Taken together, our results demonstrate that PN-101 has therapeutic potential to attenuate pathological inflammatory responses.
The study was conducted to evaluate the effects of carboxymethyl chitosan (CMC) on proliferation, migration, and lipopolysaccharide (LPS)-induced inflammatory response in canine bone marrow-derived mesenchymal stem cells (BMSCs). The proliferation and migration of BMSCs were examined after treatment with CMC. The effect of CMC on the mRNA expression of inflammatory cytokines, such as interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, IL-10, and transforming growth factor (TGF)-β, was also evaluated by reverse transcription polymerase chain reaction (RT-PCR). In the proliferation assay, no significant changes were found at all CMC concentrations compared with controls. The migration assay showed that CMC dose-dependently stimulated the migration of BMSCs in normal and LPS-treated conditions. RT-PCR showed that TNF-α and IL-10 expressions were suppressed in the BMSCs after CMC treatment. However, other genes were not affected. Taken together, CMC promoted BMSC migration and inhibited TNF-α and IL-10. Therefore, CMC may be possible to regulate wound healing when mesenchymal stem cells are applied in inflammatory diseases.
Jang, Kwangsik;Jo, Hyun Min;Shim, Kyung Mi;Kim, Se Eun;Kang, Seong Soo
Journal of Veterinary Clinics
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v.39
no.2
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pp.59-64
/
2022
A dog aged two years and seven months and a cat aged seven years were referred owing to fractures of long bones. Preoperative radiographs revealed comminuted bone fractures close to joints. Conventionally, long-bone fractures are treated using intramedullary pins, plate and screw systems, or an external fixator system. In cases of non-reducible fractures, various graft materials have been used in fracture treatments to stimulate bone repair. Here, recombinant human bone morphogenetic protein-2 (rhBMP-2) and a collagen membrane were applied. Four weeks after surgery, fractured bone fragments began to unite and the bone union was observed using radiography four months after surgery. No complications occurred related to grafted materials. We successfully applied rhBMP-2 and collagen membranes in two different species to support the healing process of comminuted fractures, according to the concept of guided bone regeneration.
Cancer is the first leading cause of death in Korea and the second leading cause of death in the USA. There is extensive research into prevention of cancer and the support of oncology patients with diet or dietary supplements. In vitro and in vivo animal studies have indicated that antioxidants, including beta-carotene, alpha-tocopherol, and ascorbic acid, can yield anti-cancer effects in addition to providing protection against oxidative damage. Although many observational studies have shown that consuming fruits and vegetables can reduce the risk of some cancers, the results of several large-scale human intervention trials testing the benefits of a single or combined higher-dose of individual micronutrients have been inconsistent. Cancer can cause profound metabolic and physiological changes which may affect patients' nutrient requirements. Although the optimal route of nutrient delivery is through diet, cancer patients often suffer symptoms that disrupt their food intake, including anorexia, premature satiety, altered taste and smell, and changes in bowel mobility. In particular, micronutrient deficits can slow postoperative healing, contribute to depression symptoms, and decrease immune competence. Cancer patients are generally motivated to take dietary supplements to improve responses to treatment and quality of life. The Physician's Health Study II (PHS II) randomized controlled trial reported recently that daily multivitamin supplementation significantly, albeit modestly, reduced the risk of total cancer. Although evidence of multivitamin use benefits is limited in cancer patients, taking dietary supplements with constituents in the range of the recommended daily allowance according to the Dietary Reference Intake (DRI) recommendation is generally considered to be safe.
Background: The need for a storage method capable of preserving the intrinsic properties of bones without using toxic substances has always been raised. Supercooling is a relatively recently introduced preservation method that meets this need. Supercooling refers to the phenomenon of liquid in which the temperature drops below its freezing point without solidifying or crystallizing. Objectives: The purpose of this study was to identify the preservation efficiency and applicability of the supercooling technique as a cortical bone allograft storage modality. Methods: The biomechanical effects of various storage methods, including deep freezing, cryopreservation, lyophilization, glycerol preservation, and supercooling, were evaluated with the three-point banding test, axial compression test, and electron microscopy. Additionally, cortical bone allografts were applied to the radial bone defect in New Zealand White rabbits to determine the biological effects. The degree of bone union was assessed with postoperative clinical signs, radiography, micro-computed tomography, and biomechanical analysis. Results: The biomechanical properties of cortical bone grafts preserved using glycerol and supercooling method were found to be comparable to those of normal bone while also significantly stronger than deep-frozen, cryopreserved, and lyophilized bone grafts. Preclinical research performed in rabbit radial defect models revealed that supercooled and glycerol-preserved bone allografts exhibited significantly better bone union than other groups. Conclusions: Considering the biomechanical and biological superiority, the supercooling technique could be one of the optimal preservation methods for cortical bone allografts. This study will form the basis for a novel application of supercooling as a bone material preservation technique.
Purpose: Platelet-rich plasma (PRP) is known to accelerate and/or enhance hard and soft tissue healing and regeneration. As such, PRP has been used in various clinical fields of surgery. Recently there have been several attempts to use PRP in the field of tissue engineering. However, some controversies still exist on exact mechanism and benefits of PRP. Therefore various animal experiments are necessary to reveal the effect of the PRP. However, even if animal experiment is performed, the efficacy of the experiment could not be validated due to absence of an animal PRP model. The purpose of this study is to establish rat PRP model by comparing several PRP fabricating methods, and to assay growth factor concentration in the PRP. Materials and methods: Rat blood samples were collected from nine SD rat (body weight: 600-800g). PRP was prepared using three different PRP fabricating methods according to previously reported literatures. (Method 1: 800 rpm, 15 minute, single centrifuge; Method 2: 1000 rpm, 10 minute, double centrifuge; Method 3: 3000 rpm, 4min and 2500 rpm, 8 min, double centrifuge). Platelet counts were evaluated in an automated machine before and after PRP fabrications. In terms of growth factor assay, prepared PRP were activated with 100 unit thrombin and 10% calcium chloride. Growth factor (PDGF-BB, VEGF) concentrations on incubation time were determined by sandwich-ELISA technique. Results: An average of 3ml (via infraorbital venous plexus) to 15ml (via celiac axis) the rat blood could be collected. By using Method 3 (3000 rpm, 4 min and 2500 rpm, 8 min, double centrifugation), around 1.5ml of PRP could be prepared. This method allowed us to concentrate platelet 3.77-fold on average. PDGF-BB concentration (mean, 1942.10 pg/ml after 1 hour incubation) and VEGF concentration (mean, 952.71 pg/ml after 1 hour incubation) in activated PRP were higher than those in untreated blood. Also PDGF-BB showed constant concentration during 4-hour incubation, while VEGF concentration was decreased after 1 hour. Conclusion: Total 11,000 g minute separation and condensation double centrifuge method can produce efficient platelet-rich plasma. Platelet-rich plasma activated with thrombin has showed higher concentrations of growth factors such as PDGF-BB and VEGF, compared to the control group. Platelet-rich plasma model in a rat model was confirmed in this study.
Park, Jung-Chul;Um, Yoo-Jung;Jung, Ui-Won;Kim, Chang-Sung;Choi, Seong-Ho;Kim, Chong-Kwan
Journal of Periodontal and Implant Science
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v.40
no.1
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pp.3-10
/
2010
Purpose: Periodontal regenerative therapies for defects created by severe periodontitis are mainly focused on bone regeneration. Although cementum regeneration needs to be better understood, it is believed to play an important role in periodontal regeneration. The first step toward a full understanding of cementum regeneration is to compare repaired cementum to pristine cementum. This study, which used histological techniques, was designed to focus on cementum regeneration and to compare pristine cementum to repaired cementum after surgical procedures with 8 and 24 week healing periods in a canine model. Methods: Buccal and lingual mucoperiosteal flaps of 10 beagle dogs were surgically reflected to create critical-sized defects. Intrabony one-wall defects, of which dimension is 4 mm width and 5 mm depth, were made at the distal aspect of mandibular second premolars and the mesial aspect of mandibular fourth premolars in the right and left jaw quadrants. Animals were sacrificed after 8 and 24 weeks post-surgery for histological specimen preparation and histometric analysis. Results: The repaired cementum was composed mostly of acellular cementum and cellular mixed fiber cementum and was thicker in the apical area than in the coronal area. The acellular cementum of the supracrestal area appeared to be amorphous. The newly formed cellular cementum was partially detached from the underlying circumpulpal dentin, which implied a weak attachment between new cementum and dentin, and this split was observed to a lesser extent in the 24 week group than in the 8 week group. The vertical height of the repaired cementum was greater in the 24 week group than in the 8 week group. Conclusions: Within the limitations of this study, we can conclude that repaired cementum after root planing was mainly acellular cementum and cementum tissue that matured to a shape similar to pristine cementum as the healing progressed from 8 to 24 weeks.
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