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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.
Enhanced bone formation by transforming growth factor-β1-releasing collagen/chitosan microgranules
Lee, Jue-Yeon,Kim, Kyoung-Hwa,Shin, Seung-Yoon,Rhyu,In-Chul,Lee, Yong-Moo,Park, Yoon-Jeong,Chung, Chong-Pyoung,Lee, Seung-Jin 이화여자대학교 약학연구소 2008 藥學硏究論文集 Vol.- No.17
Collagen/chitosan composite microgranules were fabricated as bone substitutes for the purpose of obtaining high bone-forming efficacy. The microgranules have the flexibility to fill various types of defect sites with closer packing. The interconnected pores formed spaces between the microgranules, which allowed new bone ingrowth and vascularization. In addition, the transforming growth factorbeta 1 (TGF-β1) was incorporated into the microgranules in order to improve bone-healing efficacy. The collagen/chitosan microgranules were fabricated by dropping a mixed solution into a NaOH/ethanol solution. TGF-β1 was loaded into the collagen/chitosan microgranules by soaking the microgranules in a TGF-β1 solution. Scanning electron microscopy (SEM) observations and experiments examining the release of TGF-β1 from chitosan and the collagen/chitosan microgranules were performed. SEM was used to examine the cell morphologies on the microgranules and cell proliferation was evaluated using a dimethylthiazole tetrazolium bromide assay. The differentiated cell function was assessed by measuring the alkaline phosphatase(ALPase) activity as well as detecting an osteocalcin assay. The in vivo bone-regeneration experiments were performed using a rabbit calvarial defect model. TGF-β1 was released from the collagen/chitosan microgranules at a therapeutic concentration for 4 weeks. SEM indicated that the seeded osteoblastic cells were firmly attached to the microgranules and proliferated in a multilayer manner. The proliferation of the osteoblasts on the TGF-β1-loaded microgranules was the highest among the different types of microgranules tested. The ALPase activity and osteocalcin level of all the samples increased during the culture period, and the TGF-β1-loaded microgranules had a significantly higher ALPase activity and osteocalcin content than other microgranules. The TGF-β1-loaded microgranules demonstrated a higher bone regenerative capacity in the rabbit calvarial defects after 4 weeks than the TGF-β-unloaded microgranules. ⓒ 2005 Wiley Periodicals, Inc. J Biomed Mater Res 76A: 530-539, 2006
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,Seol, Yang-Jo,Kim, Kyoung-Hwa,Lee, Yong-Moo,Park, Yoon-Jeong,Rhyu, In-Chul,Chung, Chong-Pyoung,Lee, Seung-Jin 이화여자대학교 약학연구소 2004 藥學硏究論文集 Vol.- No.14
Purpose. Tricalcium phosphate (TCP)/chitosan composite microgranules were developed as bone substitutes and tissue engineering scaffolds with the aim of obtaining a high bone forming efficacy. The microgranules have the ability to fill various types of defect sites with closer packing. In addition. the transforming growth factor-beta I(TGF-β1) was added to the microgranules in order to improve bonehealing efficacy. Methods. TCP/chitosan microgranules were fabricated by dropping a TCP suspended chitosan solution into a NaOH/ethanol solution. TGF-β1 was incorporated into the TCP/chitosan microgranules by soaking the microgranules into the TGF-β1 solution. Scanning electron microscopy(SEM) observations as well as experiments examining the release of TGF-β1 from chitosan and TCP/chitosan microgranules were performed. SEM was used to examine the cell morphologies on the microgranules, and the extent of cell proliferation was evaluated using a dimethyl-thiazol tetrazolium bromide (MTT) assay. The differentiated cell function was assessed by measuring the alkaline phosphatase activity as well as performing an osteocalcin assay. Results. The size of the prepared microgranules was 350-500㎛ and TCP powders were observed on the surface of the microgranules. TGF-β1 was released from the TCP/chitosan microgranules at a therapeutic concentration for 4 weeks. The proliferation of osteoblasts on the TGF-β1 loaded microgranules was the highest among the microgranules. SEM indicated that the seeded osteoblastice cells were firmly attached to the microgranules and proliferated in a multilayer fashion. The ALPase activity and osteocalcin content of all the samples increased during the culture period Conclusions. These results suggest that the TCP/chitosan microgranules are potential bone substitutes with a drug releasing capacity and a osteoblastic cells culture scaffold.
Biological effects of a porcine-derived collagen membrane on intrabony defects
Lee, Chang-Kyun,Koo, Ki-Tae,Kim, Tae-Il,Seol, Yang-Jo,Lee, Yong-Moo,Rhyu, In-Chul,Ku, Young,Chung, Chong-Pyoung,Park, Yoon-Jeong,Lee, Jue-Yeon Korean Academy of Periodontology 2010 Journal of Periodontal & Implant Science Vol.40 No.5
Purpose: To prolong the degradation time of collagen membranes, various cross-linking techniques have been developed. For cross-linking, chemicals such as formaldehyde and glutaraldehyde are added to collagen membranes, but these chemicals could adversely affect surrounding tissues. The aim of this study is to evaluate the ability of porous non-chemical cross-linking porcine-derived collagen nanofibrous membrane to enhance bone and associated tissue regeneration in one-wall intrabony defects in beagle dogs. Methods: The second and third mandibular premolars and the first molars of 2 adult beagles were extracted bilaterally and the extraction sites were allowed to heal for 10 weeks. One-wall intrabony defects were prepared bilaterally on the mesial and distal side of the fourth mandibular premolars. Among eight defects, four defects were not covered with membrane as controls and the other four defects were covered with membrane as the experimental group. The animals were sacrificed 10 weeks after surgery. Results: Wound healing was generally uneventful. For all parameters evaluating bone regeneration, the experimental group showed significantly superior results compared to the control. In new bone height (NBh), the experimental group exhibited a greater mean value than the control ($3.04{\pm}0.23\;mm/1.57{\pm}0.59$, P=0.003). Also, in new bone area (NBa) and new bone volume (NBv), the experimental group showed superior results compared to the control (NBa, $34.48{\pm}10.21%$ vs. $5.09{\pm}5.76%$, P=0.014; and NBv, $28.04{\pm}12.96$ vs. $1.55{\pm}0.57$, P=0.041). On the other hand, for parameters evaluating periodontal tissue regeneration, including junctional epithelium migration and new cementum height, there were no statistically significant differences between two groups. Conclusions: Within the limitations of this study, this collagen membrane enhanced bone regeneration at one-wall intrabony defects. On the other hand, no influence of this membrane on periodontal tissue regeneration could be ascertained in this study.
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>