• International Journal of Stem Cells
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• v.16 no.1
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• pp.1-15
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• 2023

Liver organoids have gained much attention in recent years for their potential applications to liver disease modeling and pharmacologic drug screening. Liver organoids produced in vitro reflect some aspects of the in vivo physiological and pathological conditions of the liver. However, the generation of liver organoids with perfusable luminal vasculature remains a major challenge, hindering precise and effective modeling of liver diseases. Furthermore, vascularization is required for large organoids or assembloids to closely mimic the complexity of tissue architecture without cell death in the core region. A few studies have successfully generated liver organoids with endothelial cell networks, but most of these vascular networks produced luminal structures after being transplanted into tissues of host animals. Therefore, formation of luminal vasculature is an unmet need to overcome the limitation of liver organoids as an in vitro model investigating different acute and chronic liver diseases. Here, we provide an overview of the unique features of hepatic vasculature under pathophysiological conditions and summarize the biochemical and biophysical cues that drive vasculogenesis and angiogenesis in vitro. We also highlight recent progress in generating vascularized liver organoids in vitro and discuss potential strategies that may enable the generation of perfusable luminal vasculature in liver organoids.

• BMB Reports
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• v.50 no.2
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• pp.58-59
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• 2017

The beneficial paracrine roles of mesenchymal stem cells (MSCs) in tissue repair have potential in therapeutic strategies against various diseases. However, the key therapeutic factors secreted from MSCs and their exact molecular mechanisms of action remain unclear. In this study, the cell-free secretome of umbilical cord-derived MSCs showed significant anti-fibrotic activity in the mouse models of liver fibrosis. The involved action mechanism was the regulation of hepatic stellate cell activation by direct inhibition of the $TGF{\beta}$/Smad-signaling. Antagonizing the milk fat globule-EGF factor 8 (MFGE8) activity blocked the anti-fibrotic effects of the MSC secretome in vitro and in vivo. Moreover, MFGE8 was secreted by MSCs from the umbilical cord as well as other tissues, including teeth and bone marrow. Administration of recombinant MFGE8 protein alone had a significant anti-fibrotic effect in two different models of liver fibrosis. Additionally, MFGE8 downregulated $TGF{\beta}$ type I receptor expression by binding to ${\alpha}v{\beta}3$ integrin on HSCs. These findings revealed the potential role of MFGE8 in modulating $TGF{\beta}$-signaling. Thus, MFGE8 could serve as a novel therapeutic agent for liver fibrosis.

• Journal of Periodontal and Implant Science
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• v.31 no.1
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• pp.57-74
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• 2001

The purpose of this study was to evaluate the adjunctive combined effect of demineralized freeze-dried bone allograft(DFDB) in guided bone regeneration on supra-alveo-lar peri-implant defect. Supra-alveolar perio-implant defects, 3mm in height, each including 4 IMZ titanium plasma-sprayed implants were surgically created in two mongrel dogs. Subsequently, the defects were treated with 1 of the following 3 modalities: Control) no membrane or graft application, Group1) DFDB application, Group2) guided bone regeneration using an expanded polytetra-fluoroethylene membrane, Group3) guided bone regeneration using membrane and DFDB. After a healing period of 12-week, the animals were sacrificed, tissue blocks were harvested and prepared for histological analysis. Histologic examination were as follows; 1. New bon formation was minimal in control and Group 1, but considerable new bone formation was observed in Group 2 and Group 3. 2. There was no osteointegration at the implant-bone interface in the high-polished area of group2 and Group 3. 3. In fluorescent microscopic examination, remodeling of new bone was most active during week 4 and week 8. There was no significant difference in remodeling rate between group 2 and group 3. 4. DFDB particles were observed, invested in a connective tissue matrix. Osteoblast activity in the area was minimal. The results suggest that guided bone regeneration shows promising results in supra-alveolar peri-implant defects during the 12 week healing period although it has a limited potential in promoting alveolar bone regeneration in the high-polished area. There seems to be no significant adjunctive effect when DFDB is combined with GBR.

• Journal of Periodontal and Implant Science
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• v.43 no.6
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• pp.315-322
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• 2013

Purpose: In this study, we investigated the effect of silk scaffolds on one-wall periodontal intrabony defects. We conjugated nano-hydroxyapatite (nHA) onto a silk scaffold and then seeded periodontal ligament cells (PDLCs) or dental pulp cells (DPCs) onto the scaffold. Methods: Five dogs were used in this study. Bilateral 4 mm${\times}$2 mm (depth${\times}$mesiodistal width), one-wall intrabony periodontal defects were surgically created on the distal side of the mandibular second premolar and the mesial side of the mandibular fourth premolar. In each dog, four of the defects were separately and randomly assigned to the following groups: the PDLCcultured scaffold transplantation group (PDLC group), the DPC-cultured scaffold transplantation group (DPC group), the normal saline-soaked scaffold transplantation group, and the control group. The animals were euthanized following an 8-week healing interval for clinical, scanning electron microscopy (SEM), and histologic evaluations. Results: There was no sign of inflammation or other clinical signs of postoperative complications. The examination of cellseeded constructs by SEM provided visual confirmation of the favorable characteristics of nHA-coated silk scaffolds for tissue engineering. The scaffolds exhibited a firm connective porous structure in cross section, and after PDLCs and DPCs were seeded onto the scaffolds and cultured for 3 weeks, the attachment of well-spread cells and the formation of extracellular matrix (ECM) were observed. The histologic analysis revealed that a well-maintained grafted volume was present at all experimental sites for 8 weeks. Small amounts of inflammatory cells were seen within the scaffolds. The PDLC and DPC groups did not have remarkably different histologic appearances. Conclusions: These observations indicate that nHA-coated silk scaffolds can be considered to be potentially useful biomaterials for periodontal regeneration.

• Journal of Periodontal and Implant Science
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• v.30 no.1
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• pp.167-180
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• 2000

The present study evaluated the effects of guided tissue regeneration using biodegradable membrane, with and without calcium-phosphate thin film coated deproteinated bone powder in beagle dogs. Contralateral fenestration defects(6 × 4 mm) were created 4 mm apical to the buccal alveolar crest on maxillary canine teeth in 5 beagle dogs. Ca-P thin film coated deproteinated bone powder was implanted into one randomly selected fenestration defect(experimental group). Biodegradable membranes were used to provide bilateral GTR. Tissue blocks including defects with overlying membranes and soft tissues were harvested following a four- & eight-week healing interval and prepared for histologic analysis. The results of this study were as follows. 1.......The regeneration of new bone, new periodontal ligament, and new cementum was occurred in experimental group more than control group. 2.......The collapse of biodegradable membranes into defects were showed in control group and the space for regeneration was diminished. In experimental group, the space was maintained without collapse by graft materials. 3........In experimental group, the graft materials were resorbed at 4 weeks after surgery and regeneration of bone surrounding graft materials was occurred at 8 weeks after surgery. 4.......Biodegradable membranes were not resorbed at 4 weeks and partial resorption was occurred at 8 weeks but the framework and the shape of membranes were maintained. No inflammation was showed at resorption. In conclusion, the results of the present study suggest that Ca-P thin film coated deproteinated bone powder has adjunctive effect to GTR in periodontal fenestration defects. Because it has osteoconductive property and prohibit collapse of membrane into defect, can promote regeneration of much new attachment apparatus.

• Proceedings of the Korean Society of Precision Engineering Conference
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• 2009.06a
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• pp.51-52
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• 2009

• Journal of Periodontal and Implant Science
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• v.33 no.4
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• pp.693-703
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• 2003

The present study evaluated the effects of guided tissue regeneration using xenograft material(deproteinated bovine bone powder), with and without Calcium sulfate membrane in beagle dogs. Contralateral fenestration defects (6 ${\times}$ 4 mm) were created 4 mm apical to the buccal alveolar crest of maxillary premolar teeth in 5 beagle dogs. Deproteinated bovine bone powders were implanted into fenestration defect and one randomly covered Calcium sulfate membrane (experimental group). Calcium sulfate membrane was used to provide GTR. Tissue blocks including defects with soft tissues which were harvested following four & eight weeks healing interval, prepared for histo-phathologic analysis. The results of this study were as follows, 1. In control group, at 4 weeks after surgery, new bony trabecular contacted with interstitial tissue and osteocytes lie cell were arranged in new bony trabecule. Bony lamellation was not observed. 2. In control group , at 8 weeks after surgery, scar-like interstitial tissue was filled defect and bony trabecule form lamellation. New bony trabecular was contacted with interstitial tissue but defect was not filled yet. 3. In experimental group, at 4 weeks after surgery, new bony trabecular partially recovered around damaged bone. But new bony trabecule was observed as irregularity and lower density. 4. In experimental group, at 8 weeks after surgery, lamella bone trabecular developed around bone cavity and damaged tissue was replaced with dense interstitial tissue. In conclusion, new bone formation regenerated more in experimental than control groups and there was seen observe more regular bony trabecular in experimental than control groups at 4 weeks after surgery. In control group, at 8 weeks after surgery, the defects was filled with scar-like interstitial tissue but, in experimental group, the defects was connected with new bone. Therefore xenograft material had osteoconduction but could not fill the defects. We thought that the effective regeneration of periodontal tissue, could be achieved using GTR with Calcium sulfate membrane.

• Journal of Periodontal and Implant Science
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• v.45 no.6
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• pp.229-237
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• 2015

Purpose: The aim of this study was to determine the clinical feasibility of using dehydrothermally cross-linked collagen membrane (DCM) for bone regeneration around peri-implant dehiscence defects, and compare it with non-cross-linked native collagen membrane (NCM). Methods: Dehiscence defects were investigated in twenty-eight patients. Defect width and height were measured by periodontal probe immediately following implant placement (baseline) and 16 weeks afterward. Membrane manipulation and maintenance were clinically assessed by means of the visual analogue scale score at baseline. Changes in horizontal thickness at 1 mm, 2 mm, and 3 mm below the top of the implant platform and the average bone density were assessed by cone-beam computed tomography at 16 weeks. Degradation of membrane was histologically observed in the soft tissue around the implant prior to re-entry surgery. Results: Five defect sites (two sites in the NCM group and three sites in the DCM group) showed soft-tissue dehiscence defects and membrane exposure during the early healing period, but there were no symptoms or signs of severe complications during the experimental postoperative period. Significant clinical and radiological improvements were found in all parameters with both types of collagen membrane. Partially resorbed membrane leaflets were only observed histologically in the DCM group. Conclusions: These findings suggest that, compared with NCM, DCM has a similar clinical expediency and possesses more stable maintenance properties. Therefore, it could be used effectively in guided bone regeneration around dehiscence-type defects.

• Journal of Periodontal and Implant Science
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• v.29 no.3
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• pp.447-472
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• 1999

The preclinical and clinical studies reviewed herein show that rhBMP-2 induces normal physiologic bone in relevant defects in the craniofacial skeleton. The newly formed bone assumes characteristics of the adjacent resident bone, and allows placement and osseointegration of dental implants. Clearly, the bone inducing capacity of rhBMP-2 is carrier and site dependent. rhBMP-2 in an absorbable collagen sponge carrier induces relevant bone formation in space providing defects. Space providing carries extends this possibility to non-space providing sites. Notably, some ceramic and polymeric biomaterials may substantially interfere with rhBMP-2 induced osteogenesis.

• Journal of Periodontal and Implant Science
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• v.34 no.1
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• pp.163-175
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• 2004

This study was performed to evaluate bone formation in the calvaria of rabbit by the concept of guided bone regeneration with titanium mesh membrane and demineralized freeze-dried bone. The animal was sacrificed at 2 weeks, 4 weeks, 8 weeks, and 12 weeks after the surgery. Non-decalcified specimens were processed for histologic analysis. 1. The titanium mesh but the biocompatibility was excellent the cell-occlusiveness was feeble. 2. The cell-occlusiveness was feeble and also the soft tissue growth of the upper part of the newly-formed bone after operating was excellent in early stage. 3. The maintenance ability of the space for the GBR very was excellent. 4. The titanium mesh the tissue-integration was superior the wound fixation ability excellent. 5. The demineralized freeze-dried bone did not promote the bone regeneration. 6. With the lapse of time, formation quantity of the bone some it increased, it increased quantity very it was feeble. Within the above results, the titanium mesh for the guided bone regeneration was excellent, the dεmineralized freeze-dried bone confirmed does not promote bone regeneration.