Tissue engineering is an emerging, innovative technology to improve or replace the biological functions of damaged tissues and organs. Scaffolds are important materials for tissue engineering as they support cell attachment, migration, and differentiation. Marine sponges naturally contain scaffolds formed by extracellular matrix proteins (collagen and sponging) and strengthened by a siliceous or calcium carbonate skeleton. Coral skeletons are also derived naturally formed by essential calcium carbonate in the form of aragonite, and are similar to human bone. In addition, collagen extracted from jellyfish is a biosafe alternative to bovine and porcine collagen and gained attention as a potential source for tissue engineering. Moreover, cuttlefish bone is an excellent calcium source and can be used to generate bio-synthetic calcium phosphate. It has become a natural candidate for biomimetic scaffolds. This review describes the use of natural products derived from marine invertebrates for applications in bone tissue engineering based on studies from 2008 to 2014.
Journal of the Korean Society for Precision Engineering
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v.27
no.9
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pp.52-57
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2010
The analysis of a crack in a bone-like material is performed numerically. The bone-like material is hierarchically structured and each hierarchy is structured by mineral platelets and protein matrix through staggered arrangement. Mechanical behavior of the composite can be analyzed using tension shear chain model. The Dugdale model is adopted to evaluate the fracture energy of Bone-like material. The fracture energy dissipation is assumed to concentrate within a strip near the crack tip along the prospective crack path. Fracture criterion of the bone-like material is estimated by using J integral. Effects of hierarchical level, ratio of elastic modulus of mineral to protein, aspect ratio of mineral platelet and volume fraction on J integral are investigated. It is found that the J integral decreases as elastic modulus ratio and hierarchy level increase. It is also shown that the J integral increases as the volume fraction and aspect ratio decrease.
Bone morphogenetic protein 1 (BMP-1) is part of a complex capable of inducing ectopic bone formation in mammals. Studies on TGF-β1 processing and Drosophila dorsal-ventral patterning have focused attention on BMP-1 as important in mediating the biological activity of this bone inducing complex. Herein, the bacterial expression, refolding, purification, and initial characterization of the BMP-1 proteolytic domain (BPD) are described. A semi-quantitative fluorescence-based thin layer chromatography assay was developed to assist in rapidly screening for optimal renaturation conditions. According to a preliminary screen for optimal conditions for the refolding of BPD , a detectable proteolytic activity against a high turnover substrate for astacin, a homologous protease from crayfish was observed. The conditions identified have allowed the expression of sufficient amounts of BPD for the characterization of the protein. Its proteolytic activity exhibits the same cleavage specificity as astacin against seven substrates that were previously synthesized for studying astacin. Furthermore, this activity is inhibited by the metal chelator 1,10-phenanthroline but not by its analogue 1,7-phenanthroline. The collagenase inhibitor Pro-Leu-Gly hydroxamate was found to inhibit both astacin and BPD activity. The results presented in this paper argue that BMP-1 does in fact possess an intrinsic proteolytic activity.
Kim, Young-Kyun;Lee, Junho;Kim, Kyung-Wook;Um, In-Woong;Murata, Masaru;Ito, Katsutoshi
Maxillofacial Plastic and Reconstructive Surgery
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v.35
no.6
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pp.353-359
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2013
Purpose: Extensive research is actively ongoing for development of an ideal bone substitute that meets the gold standard. Tooth was selected as a donor site for evaluation of potentials in bone substitutes based on its similar chemical compositions to alveolar bone. Previous studies have evaluated inorganic components of autogenous tooth bone graft material (AutoBT) and osteoconductivity. In continuation from the previous studies, the current study was conducted for analysis of organic components and evaluation of osteoinductivity of AutoBT. Methods: Forty-six extracted teeth were collected from actual patients (Korea Tooth Bank, R&D Institute). Extracted teeth were processed into AutoBT and implanted in dorsal subcutaneous muscular tissues of 15 athymic mice. Biopsy samples were harvested at two, five, and eight weeks. The Bradford assay, sodium dodecyl sulphate polyacrylamide gradient gel, and western blotting were performed for investigation of organic contents of AutoBT. Results: Histology analyses showed signs of new bone formation as early as two weeks. Results of the Bradford assay indicated the existence of noncollagenous proteins (NCP). 0.29% (2.89 mg/g) of proteins were extracted by weight in the root portion of AutoBT; 0.02% (0.029 mg/g) and 1.79% (17.93 mg/g) of proteins were measured by weight in crown and block-form of AutoBT, respectively. However, recombinant human bone morphogenetic protein-2 was not observed in AutoBT. Conclusion: Within the limitation of the current study, AutoBT induced new bone formation by NCP embedded in dentin.
Proceedings of the Korean Institute of Surface Engineering Conference
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2017.05a
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pp.79-79
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2017
Metallic biomaterials have been mainly used for the fabrication of medical devices for the replacement of hard tissue such as artificial hip joints, bone plates, and dental implants. Because they are very reliable on the viewpoint of mechanical performance. This trend is expected to continue. Especially, Ti and Ti alloys are bioinert. So, they do not chemically bond to the bone, whereas they physically bond with bone tissue. For their poor surface biocompatibility, the surface of Ti alloys has to be modified to improve the surface osteoinductivity. Recently, ceramic-like coatings on titanium, produced by plasma electrolytic oxidation (PEO), have been developed with calciumand phosphorus-enriched surfaces. A lso included the influences of coatings, which can accelerate healing and cell integration, as well as improve tribological properties. However, the adhesions of these coatings to the Ti surface need to be improved for clinical use. Particularly Silicon (Si) has been found to be essential for normal bone, cartilage growth and development. This hydroxyapatite, modified with the inclusion of small concentrations of silicon has been demonstrating to improve the osteoblast proliferation and the bone extracellular matrix production. Strontium-containing hydroxyapatite (Sr-HA) was designed as a filling material to improve the biocompatibility of bone cement. In vitro, the presence of strontium in the coating enhances osteoblast activity and differentiation, whereas it inhibits osteoclast production and proliferation. The objective of this work was to study Morphology of bone-like apatite formation on Sr and Si-doped hydroxyapatite surface of Ti-6Al-4V alloy after plasma electrolytic oxidation. Anodized alloys was prepared at 270V~300V voltages with various concentrations of Si and Sr ions. Bone-like apatite formation was carried out in SBF solution. The morphology of PEO, phase and composition of oxide surface of Ti-6Al-4V alloys were examined by FE-SEM, EDS, and XRD.
Brown tumor is the benign bone lesion consists of woven bone and fibrous tissue without matrix, which develop due to chronic excessive osteoclastic activity such as hyperparathyroidism. Usually they appear with normal uptake or occasionally focally increased uptake on bone scan. We present a case with brown tumor shown more increased uptake and more number of lesions on bone scan after parathyroidectomy, and lesser increased uptake on serial bone scans without any other treatment through several months. This finding is thought to be similar to 'flare phenomenon' which is occasionally seen after treatment of metastatic bone lesions of malignant cancer, and may represent curative process of brown tumor with rapid normal bone formation.
Kim, Yu Li;Lee, Sun Kyoung;Park, Kwang-Kyun;Chung, Won-Yoon
Journal of Cancer Prevention
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v.21
no.2
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pp.88-94
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2016
Background: Breast cancer is the most common malignant disease in women. The patients with advanced breast cancer develop metastasis to bone. Bone metastasis and skeletal-related events by breast cancer are frequently associated with the invasiveness of breast cancer cells and osteoclasts-mediated bone resorption. Forsythia koreana is used in oriental traditional medicine to treat asthma, atopy, and allergic diseases. The aim of this study was to evaluate the inhibitory effects of F. koreana extracts on the invasion of breast cancer cells and bone resorption by osteoclasts. Methods: Cell viability was measured by an MTT assay and the migration and invasion of MDA-MB-231 cells were detected by a Boyden chamber assay. The formation of osteoclasts and pit was detected using tartrate-resistant acid phosphatase staining and calcium phosphate-coated plates, respectively. The activities of matrix metalloproteinases (MMPs) and cathepsin K were evaluated by gelatin zymography and a cathepsin K detection kit. Results: The fruit and leaf extracts of F. koreana significantly inhibited the invasion of MDA-MB-231 cells at noncytotoxic concentrations. The fruit extract of F. koreana reduced the transforming growth factor ${\beta}1-induced$ migration, invasion and MMPs activities of MDA-MB-231 cells. In addition, the fruit, branch, and leaf extracts of F. koreana also inhibited the receptor activator of nuclear factor kappa-B ligand-induced osteoclast formation and osteoclast-mediated bone-resorbing activity by reducing the activities of MMPs and cathepsin K. Conclusions: The extracts of F. koreana may possess the potential to inhibit the breast cancer-induced bone destruction through blocking invasion of breast cancer cells, osteoclastogenesis, and the activity of mature osteoclasts.
Metal matrix composites(MMC) consist of metal matrix into which is distributed a second solid phase. The normal intension is to develop a material with superior mechanical properties (for example increased toughness, stiffness and wear resistance) compared to those inherent in the matrix component. In this study, WC-12%Co/low carbon steel MMC overlays have been prepared by Gas Metal Arc Welding(GMAW) according to feeding rate of WC-12%Co grit. The macro and microstructures were examined using optical microscopy (OM) and scanning electron microscopy(SEM) each other. The characteristics of hardness and wear resistance have been investigated. WC-12%Co/low carbon steel MMC overlays which have been taken good beads without porosity and cracks were manufactured by method of GMAW. Matrix of overlayed surface was seen as fish bone and faceted dendrite structures. It was known that structures were iron tungsten carbides, Fe$_{6}$W$_{6}$C which have been occurred by melting of WC-12%Co grits. After MMC had been tested by block-roll wear test it was known that WC-12%Co/low carbon steel MMC has a excellent wear resistance by exiting Fe6w6c and WC-12%Co grit. The consequence was that region of overlay with Fe$_{6}$W$_{6}$C phase has been showed a model of adhesive wear, but region of overlay with WC-12%Co grit was restrained as a result of mechanism that wear of WC-12%Co grit is not adhesive but fracture.racture.
This study has been performed to evaluate the relationship between the remained mineral components in a decalcified bone matrix and an ectopic bone formation efficiency. The freezed rat diaphyseal cortical bones measuring 0.5cm in length were demineralized in heated 0.6N HCl at $60^{\circ}C$ for 5, 10, 15, 20, 25, 30, 35, 40 minutes, respectively, using a controlled heat ultrasonic cleaner. Each 1cc of decalcifying solution taken during decalcification procedure was used to calculate calcium content using calcium dignostics kit under 600nm of spectrophotomer. After decalcification, each specimen was also weighed. Then each prepared specimen was implanted into the dorsal pouch of 24 Sprague-Dawley rats divided into 8 groups by time course. The implants were harvested at 1, 2, and 3 weeks and prepared for routine H-E stain specimens to evaluate osteogenic activity. The results are as follows: 1. There was statistical significant difference in change of calcium concentration up to demineralization of 30 minutes and each allogenic bones decalcifed up to 20 minutes revealed 99.65% of decalcification in average. 2. There was statistical significant difference in change of weight in demineralized allogenic bone up to 20 minutes treatment but, no significant change was noted after that time. 3. The histologic analysis revealed active ectopic bone formation in the implanted allografts demineralized for 20, 25, 30 minutes, respectively. However, the other groups of allografts showed relatively poor osteoinductive activity. These findings suggest that complete decalcification with a minimized degeneration of collagen matrix is necessary to induce maximal osteogenesis by decalcified bone allograft.
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.
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