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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The use of injectable sonication-induced silk hydrogel for VEGF<sub>165</sub>
and BMP-2 delivery for elevation of the maxillary sinus floor</title>
<author><name sortKey="Zhang, Wenjie" sort="Zhang, Wenjie" uniqKey="Zhang W" first="Wenjie" last="Zhang">Wenjie Zhang</name>
<affiliation><nlm:aff id="A1">Department of Prosthodontics, Ninth People’s Hospital affiliated to Shanghai Jiao Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Oral Bioengineering and regenerative medicine Lab, Shanghai Research Institute of Stomatology, Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai 200011, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wang, Xiuli" sort="Wang, Xiuli" uniqKey="Wang X" first="Xiuli" last="Wang">Xiuli Wang</name>
<affiliation><nlm:aff id="A3">Dalian Institute of Chemical and physics, Chinese Academy of Sciences, Dalian 116023 China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A4">Department of Biomedical Engineering, School of Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wang, Shaoyi" sort="Wang, Shaoyi" uniqKey="Wang S" first="Shaoyi" last="Wang">Shaoyi Wang</name>
<affiliation><nlm:aff id="A5">Department of Oral and Maxillofacial Surgery, Ninth People’s Hospital, Shanghai JiaoTong University, School of Medicine, Shanghai 200011, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zhao, Jun" sort="Zhao, Jun" uniqKey="Zhao J" first="Jun" last="Zhao">Jun Zhao</name>
<affiliation><nlm:aff id="A5">Department of Oral and Maxillofacial Surgery, Ninth People’s Hospital, Shanghai JiaoTong University, School of Medicine, Shanghai 200011, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Xu, Lianyi" sort="Xu, Lianyi" uniqKey="Xu L" first="Lianyi" last="Xu">Lianyi Xu</name>
<affiliation><nlm:aff id="A1">Department of Prosthodontics, Ninth People’s Hospital affiliated to Shanghai Jiao Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Oral Bioengineering and regenerative medicine Lab, Shanghai Research Institute of Stomatology, Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai 200011, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zhu, Chao" sort="Zhu, Chao" uniqKey="Zhu C" first="Chao" last="Zhu">Chao Zhu</name>
<affiliation><nlm:aff id="A5">Department of Oral and Maxillofacial Surgery, Ninth People’s Hospital, Shanghai JiaoTong University, School of Medicine, Shanghai 200011, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zeng, Deliang" sort="Zeng, Deliang" uniqKey="Zeng D" first="Deliang" last="Zeng">Deliang Zeng</name>
<affiliation><nlm:aff id="A1">Department of Prosthodontics, Ninth People’s Hospital affiliated to Shanghai Jiao Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Oral Bioengineering and regenerative medicine Lab, Shanghai Research Institute of Stomatology, Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai 200011, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chen, Jake" sort="Chen, Jake" uniqKey="Chen J" first="Jake" last="Chen">Jake Chen</name>
<affiliation><nlm:aff id="A6">Division of Oral Biology, Tufts University School of Dental Medicine, One Kneeland Street, Boston, MA 02111, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zhang, Zhiyuan" sort="Zhang, Zhiyuan" uniqKey="Zhang Z" first="Zhiyuan" last="Zhang">Zhiyuan Zhang</name>
<affiliation><nlm:aff id="A5">Department of Oral and Maxillofacial Surgery, Ninth People’s Hospital, Shanghai JiaoTong University, School of Medicine, Shanghai 200011, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kaplan, David L" sort="Kaplan, David L" uniqKey="Kaplan D" first="David L." last="Kaplan">David L. Kaplan</name>
<affiliation><nlm:aff id="A4">Department of Biomedical Engineering, School of Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jiang, Xinquan" sort="Jiang, Xinquan" uniqKey="Jiang X" first="Xinquan" last="Jiang">Xinquan Jiang</name>
<affiliation><nlm:aff id="A1">Department of Prosthodontics, Ninth People’s Hospital affiliated to Shanghai Jiao Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Oral Bioengineering and regenerative medicine Lab, Shanghai Research Institute of Stomatology, Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai 200011, China</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">21889205</idno>
<idno type="pmc">3384686</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3384686</idno>
<idno type="RBID">PMC:3384686</idno>
<idno type="doi">10.1016/j.biomaterials.2011.08.047</idno>
<date when="2011">2011</date>
<idno type="wicri:Area/Pmc/Corpus">002710</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002710</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The use of injectable sonication-induced silk hydrogel for VEGF<sub>165</sub>
and BMP-2 delivery for elevation of the maxillary sinus floor</title>
<author><name sortKey="Zhang, Wenjie" sort="Zhang, Wenjie" uniqKey="Zhang W" first="Wenjie" last="Zhang">Wenjie Zhang</name>
<affiliation><nlm:aff id="A1">Department of Prosthodontics, Ninth People’s Hospital affiliated to Shanghai Jiao Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Oral Bioengineering and regenerative medicine Lab, Shanghai Research Institute of Stomatology, Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai 200011, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wang, Xiuli" sort="Wang, Xiuli" uniqKey="Wang X" first="Xiuli" last="Wang">Xiuli Wang</name>
<affiliation><nlm:aff id="A3">Dalian Institute of Chemical and physics, Chinese Academy of Sciences, Dalian 116023 China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A4">Department of Biomedical Engineering, School of Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wang, Shaoyi" sort="Wang, Shaoyi" uniqKey="Wang S" first="Shaoyi" last="Wang">Shaoyi Wang</name>
<affiliation><nlm:aff id="A5">Department of Oral and Maxillofacial Surgery, Ninth People’s Hospital, Shanghai JiaoTong University, School of Medicine, Shanghai 200011, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zhao, Jun" sort="Zhao, Jun" uniqKey="Zhao J" first="Jun" last="Zhao">Jun Zhao</name>
<affiliation><nlm:aff id="A5">Department of Oral and Maxillofacial Surgery, Ninth People’s Hospital, Shanghai JiaoTong University, School of Medicine, Shanghai 200011, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Xu, Lianyi" sort="Xu, Lianyi" uniqKey="Xu L" first="Lianyi" last="Xu">Lianyi Xu</name>
<affiliation><nlm:aff id="A1">Department of Prosthodontics, Ninth People’s Hospital affiliated to Shanghai Jiao Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Oral Bioengineering and regenerative medicine Lab, Shanghai Research Institute of Stomatology, Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai 200011, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zhu, Chao" sort="Zhu, Chao" uniqKey="Zhu C" first="Chao" last="Zhu">Chao Zhu</name>
<affiliation><nlm:aff id="A5">Department of Oral and Maxillofacial Surgery, Ninth People’s Hospital, Shanghai JiaoTong University, School of Medicine, Shanghai 200011, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zeng, Deliang" sort="Zeng, Deliang" uniqKey="Zeng D" first="Deliang" last="Zeng">Deliang Zeng</name>
<affiliation><nlm:aff id="A1">Department of Prosthodontics, Ninth People’s Hospital affiliated to Shanghai Jiao Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Oral Bioengineering and regenerative medicine Lab, Shanghai Research Institute of Stomatology, Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai 200011, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chen, Jake" sort="Chen, Jake" uniqKey="Chen J" first="Jake" last="Chen">Jake Chen</name>
<affiliation><nlm:aff id="A6">Division of Oral Biology, Tufts University School of Dental Medicine, One Kneeland Street, Boston, MA 02111, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zhang, Zhiyuan" sort="Zhang, Zhiyuan" uniqKey="Zhang Z" first="Zhiyuan" last="Zhang">Zhiyuan Zhang</name>
<affiliation><nlm:aff id="A5">Department of Oral and Maxillofacial Surgery, Ninth People’s Hospital, Shanghai JiaoTong University, School of Medicine, Shanghai 200011, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kaplan, David L" sort="Kaplan, David L" uniqKey="Kaplan D" first="David L." last="Kaplan">David L. Kaplan</name>
<affiliation><nlm:aff id="A4">Department of Biomedical Engineering, School of Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jiang, Xinquan" sort="Jiang, Xinquan" uniqKey="Jiang X" first="Xinquan" last="Jiang">Xinquan Jiang</name>
<affiliation><nlm:aff id="A1">Department of Prosthodontics, Ninth People’s Hospital affiliated to Shanghai Jiao Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Oral Bioengineering and regenerative medicine Lab, Shanghai Research Institute of Stomatology, Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai 200011, China</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Biomaterials</title>
<idno type="ISSN">0142-9612</idno>
<idno type="eISSN">1878-5905</idno>
<imprint><date when="2011">2011</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p id="P1">Sonication-induced silk hydrogels were previously prepared as an injectable bone replacement biomaterial, with a need to improve osteogenic features. Vascular endothelial growth factor (VEGF<sub>165</sub>
) and bone morphogenic protein-2 (BMP-2) are key regulators of angiogenesis and osteogenesis, respectively, during bone regeneration. Therefore, the present study aimed at evaluating in situ forming silk hydrogels as a vehicle to encapsulate dual factors for rabbit maxillary sinus floor augmentation. Sonication-induced silk hydrogels were prepared <italic>in vitro</italic>
and the slow release of VEGF<sub>165</sub>
and BMP-2 from these silk gels was evaluated by ELISA. For <italic>in vivo</italic>
studies for each time point (4 and 12 weeks), 24 sinus floors elevation surgeries were made bilaterally in 12 rabbits for the following four treatment groups: silk gel (group Silk gel), silk gel/VEGF<sub>165</sub>
(group VEGF), silk gel/BMP-2 (group BMP-2), silk gel/VEGF<sub>165</sub>
/BMP-2 (group V+B) (n=6 per group). Sequential florescent labeling and radiographic observations were used to record new bone formation and mineralization, along with histological and histomorphometric analysis. At week 4, VEGF<sub>165</sub>
promoted more tissue infiltration into the gel and accelerated the degradation of the gel material. At this time point, the bone area in group V+B was significantly larger than those in the other three groups. At week 12, elevated sinus floor heights of groups BMP-2 and V+B were larger than those of the Silk gel and VEGF groups, and the V+B group had the largest new bone area among all groups. In addition, a larger blood vessel area formed in the remaining gel areas in groups VEGF and V+B. In conclusion, VEGF<sub>165</sub>
and BMP-2 released from injectable and biodegradable silk gels promoted angiogenesis and new bone formation, with the two factors demonstrating an additive effect on bone regeneration. These results indicate that silk hydrogels can be used as an injectable vehicle to deliver multiple growth factors in a minimally invasive approach to regenerate irregular bony cavities.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">8100316</journal-id>
<journal-id journal-id-type="pubmed-jr-id">1138</journal-id>
<journal-id journal-id-type="nlm-ta">Biomaterials</journal-id>
<journal-id journal-id-type="iso-abbrev">Biomaterials</journal-id>
<journal-title-group><journal-title>Biomaterials</journal-title>
</journal-title-group>
<issn pub-type="ppub">0142-9612</issn>
<issn pub-type="epub">1878-5905</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">21889205</article-id>
<article-id pub-id-type="pmc">3384686</article-id>
<article-id pub-id-type="doi">10.1016/j.biomaterials.2011.08.047</article-id>
<article-id pub-id-type="manuscript">NIHMS319599</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>The use of injectable sonication-induced silk hydrogel for VEGF<sub>165</sub>
and BMP-2 delivery for elevation of the maxillary sinus floor</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Zhang</surname>
<given-names>Wenjie</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wang</surname>
<given-names>Xiuli</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wang</surname>
<given-names>Shaoyi</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhao</surname>
<given-names>Jun</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Xu</surname>
<given-names>Lianyi</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhu</surname>
<given-names>Chao</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zeng</surname>
<given-names>Deliang</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chen</surname>
<given-names>Jake</given-names>
</name>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhang</surname>
<given-names>Zhiyuan</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kaplan</surname>
<given-names>David L.</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
<xref rid="FN1" ref-type="author-notes">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jiang</surname>
<given-names>Xinquan</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
<xref rid="FN1" ref-type="author-notes">*</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
Department of Prosthodontics, Ninth People’s Hospital affiliated to Shanghai Jiao Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China</aff>
<aff id="A2"><label>2</label>
Oral Bioengineering and regenerative medicine Lab, Shanghai Research Institute of Stomatology, Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai 200011, China</aff>
<aff id="A3"><label>3</label>
Dalian Institute of Chemical and physics, Chinese Academy of Sciences, Dalian 116023 China</aff>
<aff id="A4"><label>4</label>
Department of Biomedical Engineering, School of Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA</aff>
<aff id="A5"><label>5</label>
Department of Oral and Maxillofacial Surgery, Ninth People’s Hospital, Shanghai JiaoTong University, School of Medicine, Shanghai 200011, China</aff>
<aff id="A6"><label>6</label>
Division of Oral Biology, Tufts University School of Dental Medicine, One Kneeland Street, Boston, MA 02111, USA</aff>
<author-notes><corresp id="FN1"><label>*</label>
Co-corresponding authors Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China. Tel.: +86 21 63135412. Fax: +86 21 63136856. <email>xinquanj@yahoo.cn</email>
, School of Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA. Tel: +1 617 627 3251. Fax: +1 617 627 3231. <email>david.kaplan@tufts.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>5</day>
<month>10</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="epub"><day>01</day>
<month>9</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="ppub"><month>12</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>01</day>
<month>12</month>
<year>2012</year>
</pub-date>
<volume>32</volume>
<issue>35</issue>
<fpage>9415</fpage>
<lpage>9424</lpage>
<permissions><copyright-statement>© 2011 Elsevier Ltd. All rights reserved.</copyright-statement>
<copyright-year>2011</copyright-year>
</permissions>
<abstract><p id="P1">Sonication-induced silk hydrogels were previously prepared as an injectable bone replacement biomaterial, with a need to improve osteogenic features. Vascular endothelial growth factor (VEGF<sub>165</sub>
) and bone morphogenic protein-2 (BMP-2) are key regulators of angiogenesis and osteogenesis, respectively, during bone regeneration. Therefore, the present study aimed at evaluating in situ forming silk hydrogels as a vehicle to encapsulate dual factors for rabbit maxillary sinus floor augmentation. Sonication-induced silk hydrogels were prepared <italic>in vitro</italic>
and the slow release of VEGF<sub>165</sub>
and BMP-2 from these silk gels was evaluated by ELISA. For <italic>in vivo</italic>
studies for each time point (4 and 12 weeks), 24 sinus floors elevation surgeries were made bilaterally in 12 rabbits for the following four treatment groups: silk gel (group Silk gel), silk gel/VEGF<sub>165</sub>
(group VEGF), silk gel/BMP-2 (group BMP-2), silk gel/VEGF<sub>165</sub>
/BMP-2 (group V+B) (n=6 per group). Sequential florescent labeling and radiographic observations were used to record new bone formation and mineralization, along with histological and histomorphometric analysis. At week 4, VEGF<sub>165</sub>
promoted more tissue infiltration into the gel and accelerated the degradation of the gel material. At this time point, the bone area in group V+B was significantly larger than those in the other three groups. At week 12, elevated sinus floor heights of groups BMP-2 and V+B were larger than those of the Silk gel and VEGF groups, and the V+B group had the largest new bone area among all groups. In addition, a larger blood vessel area formed in the remaining gel areas in groups VEGF and V+B. In conclusion, VEGF<sub>165</sub>
and BMP-2 released from injectable and biodegradable silk gels promoted angiogenesis and new bone formation, with the two factors demonstrating an additive effect on bone regeneration. These results indicate that silk hydrogels can be used as an injectable vehicle to deliver multiple growth factors in a minimally invasive approach to regenerate irregular bony cavities.</p>
</abstract>
<funding-group><award-group><funding-source country="United States">National Institute of Dental and Craniofacial Research : NIDCR</funding-source>
<award-id>R01 DE017207-01A2 || DE</award-id>
</award-group>
<award-group><funding-source country="United States">National Institute of Biomedical Imaging and Bioengineering : NIBIB</funding-source>
<award-id>P41 EB002520-01A1 || EB</award-id>
</award-group>
</funding-group>
</article-meta>
</front>
</pmc>
</record>
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