Local Controlled Release of Polyphenol Conjugated with Gelatin Facilitates Bone Formation
Catechins are extensively used in health care treatments. Nevertheless, there is scarce information about the feasibility of local administration with polyphenols for bone regeneration therapy, possibly due to lack of effective delivery systems. Here we demonstrated that the epigallocatechin-3-galla...
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creator | Honda, Yoshitomo Tanaka, Tomonari Tokuda, Tomoko Kashiwagi, Takahiro Kaida, Koji Hieda, Ayato Umezaki, Yasuyuki Hashimoto, Yoshiya Imai, Koichi Matsumoto, Naoyuki Baba, Shunsuke Shimizutani, Kimishige |
description | Catechins are extensively used in health care treatments. Nevertheless, there is scarce information about the feasibility of local administration with polyphenols for bone regeneration therapy, possibly due to lack of effective delivery systems. Here we demonstrated that the epigallocatechin-3-gallate-conjugated gelatin (EGCG/Gel) prepared by an aqueous chemical synthesis using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-morpholinium chloride (DMT-MM) gradually disintegrated with time and facilitated bone formation in a critical size defect of a mouse calvaria. Conjugation of EGCG with the Gel generated cross-linking between the two molecules, thereby leading to a retardation of the degradation of the EGCG/Gel and to a delayed release of EGCG. The prepared EGCG/Gels represented significant osteogenic capability compared with that of the uncross-linked Gel and the cross-linked Gel with uncombined-EGCG. In vitro experiments disclosed that the EGCG/Gel induced osteoblastogenesis of a mouse mesenchymal stem cell line (D1 cells) within 14 days. Using fluorescently-labeled EGCG/Gel, we found that the fraction of EGCG/Gel adsorbed onto the cell membrane of the D1 cells possibly via a Gel-cell interaction. The interaction might confer the long-term effects of EGCG on the cells, resulting in a potent osteogenic capability of the EGCG/Gel in vivo. These results should provide insight into local controlled release of polyphenols for bone therapy. |
doi_str_mv | 10.3390/ijms160614143 |
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Nevertheless, there is scarce information about the feasibility of local administration with polyphenols for bone regeneration therapy, possibly due to lack of effective delivery systems. Here we demonstrated that the epigallocatechin-3-gallate-conjugated gelatin (EGCG/Gel) prepared by an aqueous chemical synthesis using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-morpholinium chloride (DMT-MM) gradually disintegrated with time and facilitated bone formation in a critical size defect of a mouse calvaria. Conjugation of EGCG with the Gel generated cross-linking between the two molecules, thereby leading to a retardation of the degradation of the EGCG/Gel and to a delayed release of EGCG. The prepared EGCG/Gels represented significant osteogenic capability compared with that of the uncross-linked Gel and the cross-linked Gel with uncombined-EGCG. In vitro experiments disclosed that the EGCG/Gel induced osteoblastogenesis of a mouse mesenchymal stem cell line (D1 cells) within 14 days. Using fluorescently-labeled EGCG/Gel, we found that the fraction of EGCG/Gel adsorbed onto the cell membrane of the D1 cells possibly via a Gel-cell interaction. The interaction might confer the long-term effects of EGCG on the cells, resulting in a potent osteogenic capability of the EGCG/Gel in vivo. These results should provide insight into local controlled release of polyphenols for bone therapy.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms160614143</identifier><identifier>PMID: 26110386</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Animals ; Bone density ; Catechin - analogs & derivatives ; Catechin - chemistry ; Cell Differentiation - drug effects ; Delayed-Action Preparations ; Drug therapy ; Gelatin - chemistry ; Mesenchymal Stem Cells - cytology ; Mesenchymal Stem Cells - drug effects ; Mice ; Mice, Inbred ICR ; Osteogenesis - drug effects ; Osteogenesis - physiology ; Polyphenols ; Polyphenols - pharmacology ; Skull - drug effects ; Skull - pathology</subject><ispartof>International journal of molecular sciences, 2015-06, Vol.16 (6), p.14143-14157</ispartof><rights>Copyright MDPI AG 2015</rights><rights>2015 by the authors; licensee MDPI, Basel, Switzerland. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c448t-e8c2b18d9bdaf51e4881543cc12d326a27a3022105a73ed831700cbec3532a0b3</citedby><cites>FETCH-LOGICAL-c448t-e8c2b18d9bdaf51e4881543cc12d326a27a3022105a73ed831700cbec3532a0b3</cites><orcidid>0000-0002-7082-5804 ; 0000-0002-4392-2318</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490544/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490544/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26110386$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Honda, Yoshitomo</creatorcontrib><creatorcontrib>Tanaka, Tomonari</creatorcontrib><creatorcontrib>Tokuda, Tomoko</creatorcontrib><creatorcontrib>Kashiwagi, Takahiro</creatorcontrib><creatorcontrib>Kaida, Koji</creatorcontrib><creatorcontrib>Hieda, Ayato</creatorcontrib><creatorcontrib>Umezaki, Yasuyuki</creatorcontrib><creatorcontrib>Hashimoto, Yoshiya</creatorcontrib><creatorcontrib>Imai, Koichi</creatorcontrib><creatorcontrib>Matsumoto, Naoyuki</creatorcontrib><creatorcontrib>Baba, Shunsuke</creatorcontrib><creatorcontrib>Shimizutani, Kimishige</creatorcontrib><title>Local Controlled Release of Polyphenol Conjugated with Gelatin Facilitates Bone Formation</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Catechins are extensively used in health care treatments. Nevertheless, there is scarce information about the feasibility of local administration with polyphenols for bone regeneration therapy, possibly due to lack of effective delivery systems. Here we demonstrated that the epigallocatechin-3-gallate-conjugated gelatin (EGCG/Gel) prepared by an aqueous chemical synthesis using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-morpholinium chloride (DMT-MM) gradually disintegrated with time and facilitated bone formation in a critical size defect of a mouse calvaria. Conjugation of EGCG with the Gel generated cross-linking between the two molecules, thereby leading to a retardation of the degradation of the EGCG/Gel and to a delayed release of EGCG. The prepared EGCG/Gels represented significant osteogenic capability compared with that of the uncross-linked Gel and the cross-linked Gel with uncombined-EGCG. In vitro experiments disclosed that the EGCG/Gel induced osteoblastogenesis of a mouse mesenchymal stem cell line (D1 cells) within 14 days. Using fluorescently-labeled EGCG/Gel, we found that the fraction of EGCG/Gel adsorbed onto the cell membrane of the D1 cells possibly via a Gel-cell interaction. The interaction might confer the long-term effects of EGCG on the cells, resulting in a potent osteogenic capability of the EGCG/Gel in vivo. These results should provide insight into local controlled release of polyphenols for bone therapy.</description><subject>Animals</subject><subject>Bone density</subject><subject>Catechin - analogs & derivatives</subject><subject>Catechin - chemistry</subject><subject>Cell Differentiation - drug effects</subject><subject>Delayed-Action Preparations</subject><subject>Drug therapy</subject><subject>Gelatin - chemistry</subject><subject>Mesenchymal Stem Cells - cytology</subject><subject>Mesenchymal Stem Cells - drug effects</subject><subject>Mice</subject><subject>Mice, Inbred ICR</subject><subject>Osteogenesis - drug effects</subject><subject>Osteogenesis - physiology</subject><subject>Polyphenols</subject><subject>Polyphenols - pharmacology</subject><subject>Skull - drug effects</subject><subject>Skull - pathology</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkUFv1DAQhS0EoqVw5IoiceES8Hhsx7kgwYotSCu1quDAyXKc2a5XTrzECaj_HpeWquXCXGak9-lpZh5jL4G_RWz5u7AfMmiuQYLER-wYpBA157p5fG8-Ys9y3nMuUKj2KTsSGoCj0cfs-yZ5F6tVGucpxUh9dUGRXKYqbavzFK8OOxrTH2C_XLq5AL_CvKtOKbo5jNXa-RDDXIRcfUwjVes0DUVJ43P2ZOtiphe3_YR9W3_6uvpcb85Ov6w-bGovpZlrMl50YPq2691WAUljQEn0HkSPQjvROORCAFeuQeoNQsO578ijQuF4hyfs_Y3vYekG6j2VS1y0hykMbrqyyQX7UBnDzl6mn1bKlispi8GbW4Mp_Vgoz3YI2VOMbqS0ZAsGGyyl4P-obkG1SqMu6Ot_0H1aprF8wkLTCiNEo9pC1TeUn1LOE23v9gZur_O1D_It_Kv7x97RfwPF3-wAoPE</recordid><startdate>20150623</startdate><enddate>20150623</enddate><creator>Honda, Yoshitomo</creator><creator>Tanaka, Tomonari</creator><creator>Tokuda, Tomoko</creator><creator>Kashiwagi, Takahiro</creator><creator>Kaida, Koji</creator><creator>Hieda, Ayato</creator><creator>Umezaki, Yasuyuki</creator><creator>Hashimoto, Yoshiya</creator><creator>Imai, Koichi</creator><creator>Matsumoto, Naoyuki</creator><creator>Baba, Shunsuke</creator><creator>Shimizutani, Kimishige</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>7TK</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7082-5804</orcidid><orcidid>https://orcid.org/0000-0002-4392-2318</orcidid></search><sort><creationdate>20150623</creationdate><title>Local Controlled Release of Polyphenol Conjugated with Gelatin Facilitates Bone Formation</title><author>Honda, Yoshitomo ; Tanaka, Tomonari ; Tokuda, Tomoko ; Kashiwagi, Takahiro ; Kaida, Koji ; Hieda, Ayato ; Umezaki, Yasuyuki ; Hashimoto, Yoshiya ; Imai, Koichi ; Matsumoto, Naoyuki ; Baba, Shunsuke ; Shimizutani, Kimishige</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c448t-e8c2b18d9bdaf51e4881543cc12d326a27a3022105a73ed831700cbec3532a0b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Bone density</topic><topic>Catechin - analogs & derivatives</topic><topic>Catechin - chemistry</topic><topic>Cell Differentiation - drug effects</topic><topic>Delayed-Action Preparations</topic><topic>Drug therapy</topic><topic>Gelatin - chemistry</topic><topic>Mesenchymal Stem Cells - cytology</topic><topic>Mesenchymal Stem Cells - drug effects</topic><topic>Mice</topic><topic>Mice, Inbred ICR</topic><topic>Osteogenesis - drug effects</topic><topic>Osteogenesis - physiology</topic><topic>Polyphenols</topic><topic>Polyphenols - pharmacology</topic><topic>Skull - drug effects</topic><topic>Skull - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Honda, Yoshitomo</creatorcontrib><creatorcontrib>Tanaka, Tomonari</creatorcontrib><creatorcontrib>Tokuda, Tomoko</creatorcontrib><creatorcontrib>Kashiwagi, Takahiro</creatorcontrib><creatorcontrib>Kaida, Koji</creatorcontrib><creatorcontrib>Hieda, Ayato</creatorcontrib><creatorcontrib>Umezaki, Yasuyuki</creatorcontrib><creatorcontrib>Hashimoto, Yoshiya</creatorcontrib><creatorcontrib>Imai, Koichi</creatorcontrib><creatorcontrib>Matsumoto, Naoyuki</creatorcontrib><creatorcontrib>Baba, Shunsuke</creatorcontrib><creatorcontrib>Shimizutani, Kimishige</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Honda, Yoshitomo</au><au>Tanaka, Tomonari</au><au>Tokuda, Tomoko</au><au>Kashiwagi, Takahiro</au><au>Kaida, Koji</au><au>Hieda, Ayato</au><au>Umezaki, Yasuyuki</au><au>Hashimoto, Yoshiya</au><au>Imai, Koichi</au><au>Matsumoto, Naoyuki</au><au>Baba, Shunsuke</au><au>Shimizutani, Kimishige</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Local Controlled Release of Polyphenol Conjugated with Gelatin Facilitates Bone Formation</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2015-06-23</date><risdate>2015</risdate><volume>16</volume><issue>6</issue><spage>14143</spage><epage>14157</epage><pages>14143-14157</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Catechins are extensively used in health care treatments. Nevertheless, there is scarce information about the feasibility of local administration with polyphenols for bone regeneration therapy, possibly due to lack of effective delivery systems. Here we demonstrated that the epigallocatechin-3-gallate-conjugated gelatin (EGCG/Gel) prepared by an aqueous chemical synthesis using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-morpholinium chloride (DMT-MM) gradually disintegrated with time and facilitated bone formation in a critical size defect of a mouse calvaria. Conjugation of EGCG with the Gel generated cross-linking between the two molecules, thereby leading to a retardation of the degradation of the EGCG/Gel and to a delayed release of EGCG. The prepared EGCG/Gels represented significant osteogenic capability compared with that of the uncross-linked Gel and the cross-linked Gel with uncombined-EGCG. In vitro experiments disclosed that the EGCG/Gel induced osteoblastogenesis of a mouse mesenchymal stem cell line (D1 cells) within 14 days. Using fluorescently-labeled EGCG/Gel, we found that the fraction of EGCG/Gel adsorbed onto the cell membrane of the D1 cells possibly via a Gel-cell interaction. The interaction might confer the long-term effects of EGCG on the cells, resulting in a potent osteogenic capability of the EGCG/Gel in vivo. These results should provide insight into local controlled release of polyphenols for bone therapy.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>26110386</pmid><doi>10.3390/ijms160614143</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-7082-5804</orcidid><orcidid>https://orcid.org/0000-0002-4392-2318</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Animals Bone density Catechin - analogs & derivatives Catechin - chemistry Cell Differentiation - drug effects Delayed-Action Preparations Drug therapy Gelatin - chemistry Mesenchymal Stem Cells - cytology Mesenchymal Stem Cells - drug effects Mice Mice, Inbred ICR Osteogenesis - drug effects Osteogenesis - physiology Polyphenols Polyphenols - pharmacology Skull - drug effects Skull - pathology |
title | Local Controlled Release of Polyphenol Conjugated with Gelatin Facilitates Bone Formation |
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