Injectable In Situ–Forming pH/Thermo-Sensitive Hydrogel for Bone Tissue Engineering
We developed a novel pH- and thermo-sensitive hydrogel as a scaffold for autologous bone tissue engineering. We synthesized this polymer by adding pH-sensitive sulfamethazine oligomers (SMOs) to both ends of a thermo-sensitive poly(ɛ-caprolactone-co-lactide)–poly(ethylene glycol)–poly(ɛ-caprolactone...
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| Veröffentlicht in: | Tissue engineering. Part A 2009-04, Vol.15 (4), p.923-933 |
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| container_title | Tissue engineering. Part A |
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| creator | Kim, Hea Kyung Shim, Woo Sun Kim, Sung Eun Lee, Kweon-Haeng Kang, Eunah Kim, Jong-Ho Kim, Kwangmeyung Kwon, Ick Chan Lee, Doo Sung |
| description | We developed a novel pH- and thermo-sensitive hydrogel as a scaffold for autologous bone tissue engineering. We synthesized this polymer by adding pH-sensitive sulfamethazine oligomers (SMOs) to both ends of a thermo-sensitive poly(ɛ-caprolactone-co-lactide)–poly(ethylene glycol)–poly(ɛ-caprolactone-co-lactide) (PCLA-PEG-PCLA) block copolymer, yielding a pH/thermo-sensitive SMO-PCLA-PEG-PCLA-SMO block copolymer. The synthesized block copolymer solution rapidly formed a stable gel under physiological conditions (pH 7.4 and 37°C), whereas it formed a sol at pH 8.0 and 37°C, making it injectable. This pH/thermo-sensitive hydrogel exhibited high biocompatibility in a Dulbecco's modified Eagle's medium extract test. Under physiological conditions, the hydrogel easily encapsulated human mesenchymal stem cells (hMSCs) and recombinant human bone morphogenetic protein-2 (rhBMP-2), with encapsulating efficiencies of about 90% and 85%, respectively. To assay for ectopic bone formation
in vivo
, we subcutaneously injected a polymer solution containing hMSCs and rhBMP-2 into the back of mice, after which we could observe hMSC differentiation for up to 7 weeks. Histological studies revealed mineralized tissue formation and high levels of alkaline phosphatase activity in the mineralized tissue. Therefore, this pH/thermo-sensitive SMO-PCLA-PEG-PCLA-SMO block copolymer demonstrated potential as an injectable scaffold for bone tissue engineering, with
in situ
formation capabilities. |
| doi_str_mv | 10.1089/ten.tea.2007.0407 |
| format | Article |
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in vivo
, we subcutaneously injected a polymer solution containing hMSCs and rhBMP-2 into the back of mice, after which we could observe hMSC differentiation for up to 7 weeks. Histological studies revealed mineralized tissue formation and high levels of alkaline phosphatase activity in the mineralized tissue. Therefore, this pH/thermo-sensitive SMO-PCLA-PEG-PCLA-SMO block copolymer demonstrated potential as an injectable scaffold for bone tissue engineering, with
in situ
formation capabilities.</description><identifier>ISSN: 1937-3341</identifier><identifier>EISSN: 1937-335X</identifier><identifier>DOI: 10.1089/ten.tea.2007.0407</identifier><identifier>PMID: 19061427</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Alkaline Phosphatase - metabolism ; Animals ; Biomedical materials ; Bone and Bones ; Bone Morphogenetic Protein 2 - metabolism ; Bone morphogenetic proteins ; Bones ; Cell Differentiation ; Cellular biology ; Humans ; Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry ; Hydrogen-Ion Concentration ; Mesenchymal Stromal Cells - cytology ; Mesenchymal Stromal Cells - metabolism ; Methods ; Mice ; Mice, Nude ; Original Articles ; Osteogenesis - physiology ; Physiological aspects ; Polymers ; Polymers - chemistry ; Stem cells ; Temperature ; Tissue engineering ; Tissue Engineering - methods</subject><ispartof>Tissue engineering. Part A, 2009-04, Vol.15 (4), p.923-933</ispartof><rights>2009, Mary Ann Liebert, Inc.</rights><rights>COPYRIGHT 2009 Mary Ann Liebert, Inc.</rights><rights>(©) Copyright 2009, Mary Ann Liebert, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c537t-2d7213af6183b83c65ced2a2ac26460351551b2b362d427c798809b58bfcd1623</citedby><cites>FETCH-LOGICAL-c537t-2d7213af6183b83c65ced2a2ac26460351551b2b362d427c798809b58bfcd1623</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19061427$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Hea Kyung</creatorcontrib><creatorcontrib>Shim, Woo Sun</creatorcontrib><creatorcontrib>Kim, Sung Eun</creatorcontrib><creatorcontrib>Lee, Kweon-Haeng</creatorcontrib><creatorcontrib>Kang, Eunah</creatorcontrib><creatorcontrib>Kim, Jong-Ho</creatorcontrib><creatorcontrib>Kim, Kwangmeyung</creatorcontrib><creatorcontrib>Kwon, Ick Chan</creatorcontrib><creatorcontrib>Lee, Doo Sung</creatorcontrib><title>Injectable In Situ–Forming pH/Thermo-Sensitive Hydrogel for Bone Tissue Engineering</title><title>Tissue engineering. Part A</title><addtitle>Tissue Eng Part A</addtitle><description>We developed a novel pH- and thermo-sensitive hydrogel as a scaffold for autologous bone tissue engineering. We synthesized this polymer by adding pH-sensitive sulfamethazine oligomers (SMOs) to both ends of a thermo-sensitive poly(ɛ-caprolactone-co-lactide)–poly(ethylene glycol)–poly(ɛ-caprolactone-co-lactide) (PCLA-PEG-PCLA) block copolymer, yielding a pH/thermo-sensitive SMO-PCLA-PEG-PCLA-SMO block copolymer. The synthesized block copolymer solution rapidly formed a stable gel under physiological conditions (pH 7.4 and 37°C), whereas it formed a sol at pH 8.0 and 37°C, making it injectable. This pH/thermo-sensitive hydrogel exhibited high biocompatibility in a Dulbecco's modified Eagle's medium extract test. Under physiological conditions, the hydrogel easily encapsulated human mesenchymal stem cells (hMSCs) and recombinant human bone morphogenetic protein-2 (rhBMP-2), with encapsulating efficiencies of about 90% and 85%, respectively. To assay for ectopic bone formation
in vivo
, we subcutaneously injected a polymer solution containing hMSCs and rhBMP-2 into the back of mice, after which we could observe hMSC differentiation for up to 7 weeks. Histological studies revealed mineralized tissue formation and high levels of alkaline phosphatase activity in the mineralized tissue. Therefore, this pH/thermo-sensitive SMO-PCLA-PEG-PCLA-SMO block copolymer demonstrated potential as an injectable scaffold for bone tissue engineering, with
in situ
formation capabilities.</description><subject>Alkaline Phosphatase - metabolism</subject><subject>Animals</subject><subject>Biomedical materials</subject><subject>Bone and Bones</subject><subject>Bone Morphogenetic Protein 2 - metabolism</subject><subject>Bone morphogenetic proteins</subject><subject>Bones</subject><subject>Cell Differentiation</subject><subject>Cellular biology</subject><subject>Humans</subject><subject>Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry</subject><subject>Hydrogen-Ion Concentration</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Mesenchymal Stromal Cells - metabolism</subject><subject>Methods</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Original Articles</subject><subject>Osteogenesis - physiology</subject><subject>Physiological aspects</subject><subject>Polymers</subject><subject>Polymers - chemistry</subject><subject>Stem cells</subject><subject>Temperature</subject><subject>Tissue engineering</subject><subject>Tissue Engineering - methods</subject><issn>1937-3341</issn><issn>1937-335X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkcuKFDEUhgtRnIs-gBspEdxVTS6VSy3HYWa6YcDF9IC7kEqdatNUJW2SEmbnO_iGPokpulEUQQkhh8P3_5ycvyheYVRjJNuLBK5OoGuCkKhRg8ST4hS3VFSUso9Pf9YNPinOYtwhxBEX4nlxglvEcUPEafGwdjswSXcjlGtX3ts0f__67caHybptuV9dbD5BmHx1Dy7aZL9AuXrsg9_CWA4-lO-9g3JjY5yhvHZb6wBCFr4ong16jPDy-J4XDzfXm6tVdffhdn11eVcZRkWqSC8IpnrgWNJOUsOZgZ5oog3hDUeUYcZwRzrKSZ-nNaKVErUdk91geswJPS_eHXz3wX-eISY12WhgHLUDP0fFBSYSN-0_QYIY4w1BGXzzB7jzc3D5E0q2mLK82cy8PTBbPYKybvApaLMYqstsJBqBG5mp-i9UPj1M1uS9DTb3fxPgg8AEH2OAQe2DnXR4VBipJW-V885XqyVvteSdNa-P487dBP0vxTHgDIgDsLS1c6OFDkL6D-sfppO4Lw</recordid><startdate>20090401</startdate><enddate>20090401</enddate><creator>Kim, Hea Kyung</creator><creator>Shim, Woo Sun</creator><creator>Kim, Sung Eun</creator><creator>Lee, Kweon-Haeng</creator><creator>Kang, Eunah</creator><creator>Kim, Jong-Ho</creator><creator>Kim, Kwangmeyung</creator><creator>Kwon, Ick Chan</creator><creator>Lee, Doo Sung</creator><general>Mary Ann Liebert, Inc</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>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20090401</creationdate><title>Injectable In Situ–Forming pH/Thermo-Sensitive Hydrogel for Bone Tissue Engineering</title><author>Kim, Hea Kyung ; Shim, Woo Sun ; Kim, Sung Eun ; Lee, Kweon-Haeng ; Kang, Eunah ; Kim, Jong-Ho ; Kim, Kwangmeyung ; Kwon, Ick Chan ; Lee, Doo Sung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c537t-2d7213af6183b83c65ced2a2ac26460351551b2b362d427c798809b58bfcd1623</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Alkaline Phosphatase - metabolism</topic><topic>Animals</topic><topic>Biomedical materials</topic><topic>Bone and Bones</topic><topic>Bone Morphogenetic Protein 2 - metabolism</topic><topic>Bone morphogenetic proteins</topic><topic>Bones</topic><topic>Cell Differentiation</topic><topic>Cellular biology</topic><topic>Humans</topic><topic>Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry</topic><topic>Hydrogen-Ion Concentration</topic><topic>Mesenchymal Stromal Cells - cytology</topic><topic>Mesenchymal Stromal Cells - metabolism</topic><topic>Methods</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Original Articles</topic><topic>Osteogenesis - physiology</topic><topic>Physiological aspects</topic><topic>Polymers</topic><topic>Polymers - chemistry</topic><topic>Stem cells</topic><topic>Temperature</topic><topic>Tissue engineering</topic><topic>Tissue Engineering - methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Hea Kyung</creatorcontrib><creatorcontrib>Shim, Woo Sun</creatorcontrib><creatorcontrib>Kim, Sung Eun</creatorcontrib><creatorcontrib>Lee, Kweon-Haeng</creatorcontrib><creatorcontrib>Kang, Eunah</creatorcontrib><creatorcontrib>Kim, Jong-Ho</creatorcontrib><creatorcontrib>Kim, Kwangmeyung</creatorcontrib><creatorcontrib>Kwon, Ick Chan</creatorcontrib><creatorcontrib>Lee, Doo Sung</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>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</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>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science 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 Basic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Tissue engineering. Part A</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Hea Kyung</au><au>Shim, Woo Sun</au><au>Kim, Sung Eun</au><au>Lee, Kweon-Haeng</au><au>Kang, Eunah</au><au>Kim, Jong-Ho</au><au>Kim, Kwangmeyung</au><au>Kwon, Ick Chan</au><au>Lee, Doo Sung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Injectable In Situ–Forming pH/Thermo-Sensitive Hydrogel for Bone Tissue Engineering</atitle><jtitle>Tissue engineering. Part A</jtitle><addtitle>Tissue Eng Part A</addtitle><date>2009-04-01</date><risdate>2009</risdate><volume>15</volume><issue>4</issue><spage>923</spage><epage>933</epage><pages>923-933</pages><issn>1937-3341</issn><eissn>1937-335X</eissn><abstract>We developed a novel pH- and thermo-sensitive hydrogel as a scaffold for autologous bone tissue engineering. We synthesized this polymer by adding pH-sensitive sulfamethazine oligomers (SMOs) to both ends of a thermo-sensitive poly(ɛ-caprolactone-co-lactide)–poly(ethylene glycol)–poly(ɛ-caprolactone-co-lactide) (PCLA-PEG-PCLA) block copolymer, yielding a pH/thermo-sensitive SMO-PCLA-PEG-PCLA-SMO block copolymer. The synthesized block copolymer solution rapidly formed a stable gel under physiological conditions (pH 7.4 and 37°C), whereas it formed a sol at pH 8.0 and 37°C, making it injectable. This pH/thermo-sensitive hydrogel exhibited high biocompatibility in a Dulbecco's modified Eagle's medium extract test. Under physiological conditions, the hydrogel easily encapsulated human mesenchymal stem cells (hMSCs) and recombinant human bone morphogenetic protein-2 (rhBMP-2), with encapsulating efficiencies of about 90% and 85%, respectively. To assay for ectopic bone formation
in vivo
, we subcutaneously injected a polymer solution containing hMSCs and rhBMP-2 into the back of mice, after which we could observe hMSC differentiation for up to 7 weeks. Histological studies revealed mineralized tissue formation and high levels of alkaline phosphatase activity in the mineralized tissue. Therefore, this pH/thermo-sensitive SMO-PCLA-PEG-PCLA-SMO block copolymer demonstrated potential as an injectable scaffold for bone tissue engineering, with
in situ
formation capabilities.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>19061427</pmid><doi>10.1089/ten.tea.2007.0407</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Tissue engineering. Part A, 2009-04, Vol.15 (4), p.923-933 |
| issn | 1937-3341 1937-335X |
| language | eng |
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| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Alkaline Phosphatase - metabolism Animals Biomedical materials Bone and Bones Bone Morphogenetic Protein 2 - metabolism Bone morphogenetic proteins Bones Cell Differentiation Cellular biology Humans Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry Hydrogen-Ion Concentration Mesenchymal Stromal Cells - cytology Mesenchymal Stromal Cells - metabolism Methods Mice Mice, Nude Original Articles Osteogenesis - physiology Physiological aspects Polymers Polymers - chemistry Stem cells Temperature Tissue engineering Tissue Engineering - methods |
| title | Injectable In Situ–Forming pH/Thermo-Sensitive Hydrogel for Bone Tissue Engineering |
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