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Enhanced bone formation by controlled growth factor delivery from chitosan-based biomaterials
Lee, Jue-Yeon,Nam, Sung-Heon,Im, Su-Yeon,Park, Yoon-Jeong,Lee, Yong-Moo,Seol, Yang-Jo,Chung, Chong-Pyoung,Lee, Seung-Jin 梨花女子大學校 藥學硏究所 2002 藥學硏究論文集 Vol.- No.11
For the pulpose of obtaining high bone forming efficacy. developlment of chitosan was attempted as a tool useful as ascaffolding device. Porous chitosan matrices, chitosan-poiy(L-lactide) (PLLA) composite matrtices and chitosan coated onPLLA matrices were dealt with in this research. Porous chitosan matrix was fabricated by freeze-drying and cross-linkingaqueous chitosan solution. Porous chitosan matrix combined with ceramics and constituents of extracellular matrices wereprepared and examined for their bone regenerative potential. Composite porous matrix of chitosall-PLLA was prepared bymixing polyiactide with chitosan and freeze-drying. Al1 chitosan based devices demonstrated improved bone formingcapacity by increasing mechanical stability and biocompatibility. Release of platelet-derived growth factor-BB (PDGf-BH )from these matrices exerted significant osteoinductive effect in addition to the higf esteocdElducting capacity of the porouschitosan matrices. The hydrophobic surface of PLLA matrices was modified by chitosan to enhance cell affinity andwettability, The chitosan coafed PLLA matrix induced increased osteoblast attachment as compared with intact PLLAsurface. Overall results in this study demonstrated the usefulness of chitosan as drug releasing scaffolds and as modificationtools for currently used biomaterials to enhance tissue regeneration efficacy. These results may expand the feasibilitr ofcombinatfve strategy of controlled locai drug delivery concept and tissue engineered bone formation in reconstructivetherapy in the field of periodontics, orthopedics and plastic surgery.
Biological effects of a root conditioning agent for dentin surface modification in vitro
Lee, Jue-Yeon,Seol, Yang-Jo,Park, Jang-Ryul,Park, Yoon-Jeong,Chung, Chong-Pyoung Korean Academy of Periodontology 2010 Journal of Periodontal & Implant Science Vol.40 No.6
Purpose: Connective tissue reattachment to periodontally damaged root surfaces is one of the most important goals of periodontal therapy. The aim of this study was to develop a root conditioning agent that can demineralize and detoxify the infected root surface. Methods: Dentin slices obtained from human teeth were treated with a novel root planing agent for 2 minutes and then washed with phosphate-buffered saline. Smear layer removal and type I collagen exposure were observed by scanning electron microscopy (SEM) and type I collagen immunostaining, respectively. Cell attachment and lipopolysaccharides (LPS) removal demonstrated the efficiency of the root conditioning agent. Results: SEM revealed that the smear layer was entirely removed and the dentinal tubules were opened by the experimental gel. Type I collagen was exposed on the surfaces of the dentin slices treated by the experimental gel, which were compared with dentin treated with other root planing agents. Dentin slices treated with the experimental gel showed the highest number of attached fibroblasts and flattened cell morphology. The agar diffusion assay demonstrated that the experimental gel also has effective antimicrobial activity. Escherichia coli LPS were effectively removed from well plates by the experimental gel. Conclusions: These results demonstrated that this experimental gel is a useful tool for root conditioning of infected root surfaces and can also be applied for detoxification of ailing implant surface threads.
Lee, Dongwoo,Park, Kwang‐,Sook,Yoon, Gook Jin,Lee, Hyun Jung,Lee, Jue‐,Yeon,Park, Yoon Shin,Park, Joo‐,Cheol,Lee, Gene,Chung, Chong Pyoung,Park, Yoon Jeong Wiley Publishers 2019 JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Vol.107 No.11
<P><B>Abstract</B></P><P>Peptide and proteins are recognized as highly selective and therapeutically active biomaterials, as well as relatively safe in clinical application. A calcium phospholipid‐binding protein, copine 7 (CPNE7), has been recently identified to induce hard tissue regeneration, including bone and dentin by internalizing into the cells. However, the clinical application of the full length of CPNE7 has limited due to its large size with short half‐life. Herein, as an alternative to CPNE7, six bioactive synthetic peptides are designed from CPNE7 (CPNE7‐derived peptides, CDP1–CDP6) and investigated their osteogenic potential. Among the CDPs, CDP4 have the highest level of cell‐penetrating activity as well as osteogenic efficiency in dental pulp stem cells (DPSCs). CDP4 increased the expression of osteogenesis‐related genes and proteins, which was comparable to that by BMP‐2. The cell penetration capacity of CDP4 may synergistically induce the osteogenic potential of DPSCs. Moreover, the implantation of the mixture of CDP4 with injectable collagen gel increased bone formation with recovery in the mouse calvarial defect model, comparable to full‐length CPNE7 and even BMP‐2. In conclusion, these results suggest that our synthetic peptide, CDP4, can be applied in combination with biomaterial to provide high osteogenic efficacy in the field of bone tissue engineering.</P>
Cell‐penetrating chitosan/doxorubicin/TAT conjugates for efficient cancer therapy
Lee, Jue‐,Yeon,Choi, Young‐,Suk,Suh, Jin‐,Sook,Kwon, Young‐,Min,Yang, Victor C.,Lee, Seung‐,Jin,Chung, Chong‐,Pyoung,Park, Yoon‐,Jeong Wiley Subscription Services, Inc., A Wiley Company 2011 International journal of cancer: Journal internati Vol.128 No.10
<P><B>Abstract</B></P><P>In this study, a cell‐penetrating peptide, the transactivating transcriptional factor (TAT) domain from HIV, was linked to a chitosan/doxorubicin (chitosan/DOX) conjugate to form a chitosan/DOX/TAT hybrid. The synthesized chitosan/DOX/TAT conjugate showed a different intracellular distribution pattern from a conjugate without TAT. Unlike both free DOX and the conjugate without TAT, the chitosan/DOX/TAT conjugate was capable of efficient cell entry. The chitosan/DOX/TAT conjugate was found to be highly cytotoxic, with an IC<SUB>50</SUB> value of approximately 480 nM, 2 times less than that of chitosan/DOX (980 nM). The chitosan/DOX/TAT provided decreases in tumor volume of 77.4 and 57.5% compared to free DOX and chitosan/DOX, respectively, in tumor‐bearing mice. Therefore, this study suggests that TAT‐mediated chitosan/DOX conjugate delivery is effective in slowing tumor growth.</P>
Lee, Jue Yeon,Suh, Jin Sook,Kim, Jung Min,Kim, Jeong Hwa,Park, Hyun Jung,Park, Yoon Jeong,Chung, Chong Pyoung Dove Medical Press 2015 INTERNATIONAL JOURNAL OF NANOMEDICINE Vol.10 No.-
<P>Human beta-defensins (hBDs) are crucial factors of intrinsic immunity that function in the immunologic response to a variety of invading enveloped viruses, bacteria, and fungi. hBDs can cause membrane depolarization and cell lysis due to their highly cationic nature. These molecules participate in antimicrobial defenses and the control of adaptive and innate immunity in every mammalian species and are produced by various cell types. The C-terminal 15-mer peptide within hBD3, designated as hBD3-3, was selected for study due to its cell- and skin-penetrating activity, which can induce anti-inflammatory activity in lipopolysaccharide-treated RAW 264.7 macrophages. hBD3-3 penetrated both the outer membrane of the cells and mouse skin within a short treatment period. Two other peptide fragments showed poorer penetration activity compared to hBD3-3. hBD3-3 inhibited the lipopolysaccharide-induced production of inducible nitric oxide synthase, nitric oxide, and secretory cytokines, such as interleukin-6 and tumor necrosis factor in a concentration-dependent manner. Moreover, hBD3-3 reduced the interstitial infiltration of polymorphonuclear leukocytes in a lung inflammation model. Further investigation also revealed that hBD3-3 downregulated nuclear factor kappa B-dependent inflammation by directly suppressing the degradation of phosphorylated-IκBα and by downregulating active nuclear factor kappa B p65. Our findings indicate that hBD3-3 may be conjugated with drugs of interest to ensure their proper translocation to sites, such as the cytoplasm or nucleus, as hBD3-3 has the ability to be used as a carrier, and suggest a potential approach to effectively treat inflammatory diseases.</P>