A composite hydrogel with co-delivery of antimicrobial peptides and platelet-rich plasma to enhance healing of infected wounds in diabetes
Diabetic wound healing remains a major challenge due to its vulnerability to bacterial infection, as well as the less vascularization and prolonged inflammatory phase. In this study, we developed a hydrogel system for the treatment of chronic infected wounds, which can regulate inflammatory (through...
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| Veröffentlicht in: | Acta biomaterialia 2021-04, Vol.124, p.205-218 |
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| creator | Wei, Shikun Xu, Pengcheng Yao, Zexin Cui, Xiao Lei, Xiaoxuan Li, Linlin Dong, Yunqing Zhu, Weidong Guo, Rui Cheng, Biao |
| description | Diabetic wound healing remains a major challenge due to its vulnerability to bacterial infection, as well as the less vascularization and prolonged inflammatory phase. In this study, we developed a hydrogel system for the treatment of chronic infected wounds, which can regulate inflammatory (through the use of antimicrobial peptides) and enhance collagen deposition and angiogenesis (through the addition of platelet-rich plasma (PRP)). Based on the formation of Schiff base linkage, the ODEX/HA-AMP/PRP hydrogel was prepared by mixing oxidized dextran (ODEX), antimicrobial peptide-modified hyaluronic acid (HA-AMP) and PRP under physiological conditions, which exhibited obvious inhibition zones against three pathogenic bacterial strains (E. coli, S. aureus and P. aeruginosa) and slow release ability of antimicrobials and growth factors. Moreover, CCK-8, live/dead fluorescent staining and scratch test confirmed that ODEX/HA-AMP/PRP hydrogel could facilitate the proliferation and migration of L929 fibroblast cells. More importantly, in vivo experiments further demonstrated that the prepared hydrogels could significantly improve wound healing in a diabetic mouse infection by regulating inflammation, accelerating collagen deposition and angiogenesis. In addition, prepared hydrogel showed a significant antibacterial activity against S. aureus and P. aeruginosa, inhibited pro-inflammatory factors (TNF-α, IL-1β and IL-6), enhanced anti-inflammatory factors (TGF-β1) and vascular endothelial growth factor (VEGF) production. The findings of this study suggested that the composite hydrogel with AMP and PRP controlled release ability could be used as a promising candidate for chronic wound healing and infection-related wound healing.
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| doi_str_mv | 10.1016/j.actbio.2021.01.046 |
| format | Article |
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[Display omitted]</description><identifier>ISSN: 1742-7061</identifier><identifier>ISSN: 1878-7568</identifier><identifier>EISSN: 1878-7568</identifier><identifier>DOI: 10.1016/j.actbio.2021.01.046</identifier><identifier>PMID: 33524559</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Angiogenesis ; Animals ; Antibacterial activity ; Antimicrobial agents ; Antimicrobial peptide ; Antimicrobial peptides ; Bacterial diseases ; Bacterial infections ; Cell migration ; Cell proliferation ; Cholecystokinin ; Chronic infection ; Collagen ; Controlled release ; Deposition ; Dextran ; Dextrans ; Diabetes ; Diabetes Mellitus ; Diabetic infected wound ; E coli ; Escherichia coli ; Fluorescence ; Growth factors ; Hyaluronic acid ; Hydrogel ; Hydrogels ; IL-1β ; Imines ; In vivo methods and tests ; Infections ; Inflammation ; Interleukin 6 ; Mice ; Peptides ; Platelet-Rich Plasma ; Platelet-rich plasma (PRP) ; Platelets ; Pore Forming Cytotoxic Proteins ; Scratch tests ; Staphylococcus aureus ; Transforming growth factor-b1 ; Tumor necrosis factor-α ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A ; Vascularization ; Wound Healing</subject><ispartof>Acta biomaterialia, 2021-04, Vol.124, p.205-218</ispartof><rights>2021</rights><rights>Copyright © 2021. Published by Elsevier Ltd.</rights><rights>Copyright Elsevier BV Apr 1, 2021</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c441t-d0dc0c8ce990b9d130371d585ea09e5c33ca1a4fa515ffa553160ea0a74d66693</citedby><cites>FETCH-LOGICAL-c441t-d0dc0c8ce990b9d130371d585ea09e5c33ca1a4fa515ffa553160ea0a74d66693</cites><orcidid>0000-0002-7674-073X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.actbio.2021.01.046$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33524559$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wei, Shikun</creatorcontrib><creatorcontrib>Xu, Pengcheng</creatorcontrib><creatorcontrib>Yao, Zexin</creatorcontrib><creatorcontrib>Cui, Xiao</creatorcontrib><creatorcontrib>Lei, Xiaoxuan</creatorcontrib><creatorcontrib>Li, Linlin</creatorcontrib><creatorcontrib>Dong, Yunqing</creatorcontrib><creatorcontrib>Zhu, Weidong</creatorcontrib><creatorcontrib>Guo, Rui</creatorcontrib><creatorcontrib>Cheng, Biao</creatorcontrib><title>A composite hydrogel with co-delivery of antimicrobial peptides and platelet-rich plasma to enhance healing of infected wounds in diabetes</title><title>Acta biomaterialia</title><addtitle>Acta Biomater</addtitle><description>Diabetic wound healing remains a major challenge due to its vulnerability to bacterial infection, as well as the less vascularization and prolonged inflammatory phase. In this study, we developed a hydrogel system for the treatment of chronic infected wounds, which can regulate inflammatory (through the use of antimicrobial peptides) and enhance collagen deposition and angiogenesis (through the addition of platelet-rich plasma (PRP)). Based on the formation of Schiff base linkage, the ODEX/HA-AMP/PRP hydrogel was prepared by mixing oxidized dextran (ODEX), antimicrobial peptide-modified hyaluronic acid (HA-AMP) and PRP under physiological conditions, which exhibited obvious inhibition zones against three pathogenic bacterial strains (E. coli, S. aureus and P. aeruginosa) and slow release ability of antimicrobials and growth factors. Moreover, CCK-8, live/dead fluorescent staining and scratch test confirmed that ODEX/HA-AMP/PRP hydrogel could facilitate the proliferation and migration of L929 fibroblast cells. More importantly, in vivo experiments further demonstrated that the prepared hydrogels could significantly improve wound healing in a diabetic mouse infection by regulating inflammation, accelerating collagen deposition and angiogenesis. In addition, prepared hydrogel showed a significant antibacterial activity against S. aureus and P. aeruginosa, inhibited pro-inflammatory factors (TNF-α, IL-1β and IL-6), enhanced anti-inflammatory factors (TGF-β1) and vascular endothelial growth factor (VEGF) production. The findings of this study suggested that the composite hydrogel with AMP and PRP controlled release ability could be used as a promising candidate for chronic wound healing and infection-related wound healing.
[Display omitted]</description><subject>Angiogenesis</subject><subject>Animals</subject><subject>Antibacterial activity</subject><subject>Antimicrobial agents</subject><subject>Antimicrobial peptide</subject><subject>Antimicrobial peptides</subject><subject>Bacterial diseases</subject><subject>Bacterial infections</subject><subject>Cell migration</subject><subject>Cell proliferation</subject><subject>Cholecystokinin</subject><subject>Chronic infection</subject><subject>Collagen</subject><subject>Controlled release</subject><subject>Deposition</subject><subject>Dextran</subject><subject>Dextrans</subject><subject>Diabetes</subject><subject>Diabetes Mellitus</subject><subject>Diabetic infected wound</subject><subject>E coli</subject><subject>Escherichia coli</subject><subject>Fluorescence</subject><subject>Growth factors</subject><subject>Hyaluronic acid</subject><subject>Hydrogel</subject><subject>Hydrogels</subject><subject>IL-1β</subject><subject>Imines</subject><subject>In vivo methods and tests</subject><subject>Infections</subject><subject>Inflammation</subject><subject>Interleukin 6</subject><subject>Mice</subject><subject>Peptides</subject><subject>Platelet-Rich Plasma</subject><subject>Platelet-rich plasma (PRP)</subject><subject>Platelets</subject><subject>Pore Forming Cytotoxic Proteins</subject><subject>Scratch tests</subject><subject>Staphylococcus aureus</subject><subject>Transforming growth factor-b1</subject><subject>Tumor necrosis factor-α</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A</subject><subject>Vascularization</subject><subject>Wound Healing</subject><issn>1742-7061</issn><issn>1878-7568</issn><issn>1878-7568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UU2L1TAULaI44-g_EAm4cdNnbvPRdiMMg18w4EbXIU1u5-XRNjVJZ3h_wV_tfbzRhQvhktyPc0_COVX1GvgOOOj3h511ZQhx1_AGdpxC6ifVJXRtV7dKd08pb2VTt1zDRfUi5wPnooOme15dCKEaqVR_Wf26Zi7Oa8yhINsffYp3OLGHUPbUrz1O4R7TkcWR2aWEObgUh2AntuJagsdMbc_WyRacsNQpuP2pyrNlJTJc9nZxxIt2CsvdiSUsI7qCnj3EbfGZauaDHbBgflk9G-2U8dXjfVX9-PTx-82X-vbb568317e1kxJK7bl33HUO-54PvQfBRQtedQot71E5IZwFK0erQI10KgGa08y20mute3FVvTvzrin-3DAXM4fscJrsgnHLppGdUtAoAIK-_Qd6iFta6HeG5rprQYMglDyjSJycE45mTWG26WiAm5NX5mDOXpmTV4ZTSE1rbx7Jt2FG_3fpjzkE-HAGIKlxHzCZ7AKSoD4kEtH4GP7_wm_0_Ki3</recordid><startdate>20210401</startdate><enddate>20210401</enddate><creator>Wei, Shikun</creator><creator>Xu, Pengcheng</creator><creator>Yao, Zexin</creator><creator>Cui, Xiao</creator><creator>Lei, Xiaoxuan</creator><creator>Li, Linlin</creator><creator>Dong, Yunqing</creator><creator>Zhu, Weidong</creator><creator>Guo, Rui</creator><creator>Cheng, Biao</creator><general>Elsevier Ltd</general><general>Elsevier BV</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>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7674-073X</orcidid></search><sort><creationdate>20210401</creationdate><title>A composite hydrogel with co-delivery of antimicrobial peptides and platelet-rich plasma to enhance healing of infected wounds in diabetes</title><author>Wei, Shikun ; Xu, Pengcheng ; Yao, Zexin ; Cui, Xiao ; Lei, Xiaoxuan ; Li, Linlin ; Dong, Yunqing ; Zhu, Weidong ; Guo, Rui ; Cheng, Biao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c441t-d0dc0c8ce990b9d130371d585ea09e5c33ca1a4fa515ffa553160ea0a74d66693</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Angiogenesis</topic><topic>Animals</topic><topic>Antibacterial activity</topic><topic>Antimicrobial agents</topic><topic>Antimicrobial peptide</topic><topic>Antimicrobial peptides</topic><topic>Bacterial diseases</topic><topic>Bacterial infections</topic><topic>Cell migration</topic><topic>Cell proliferation</topic><topic>Cholecystokinin</topic><topic>Chronic infection</topic><topic>Collagen</topic><topic>Controlled release</topic><topic>Deposition</topic><topic>Dextran</topic><topic>Dextrans</topic><topic>Diabetes</topic><topic>Diabetes Mellitus</topic><topic>Diabetic infected wound</topic><topic>E coli</topic><topic>Escherichia coli</topic><topic>Fluorescence</topic><topic>Growth factors</topic><topic>Hyaluronic acid</topic><topic>Hydrogel</topic><topic>Hydrogels</topic><topic>IL-1β</topic><topic>Imines</topic><topic>In vivo methods and tests</topic><topic>Infections</topic><topic>Inflammation</topic><topic>Interleukin 6</topic><topic>Mice</topic><topic>Peptides</topic><topic>Platelet-Rich Plasma</topic><topic>Platelet-rich plasma (PRP)</topic><topic>Platelets</topic><topic>Pore Forming Cytotoxic Proteins</topic><topic>Scratch tests</topic><topic>Staphylococcus aureus</topic><topic>Transforming growth factor-b1</topic><topic>Tumor necrosis factor-α</topic><topic>Vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor A</topic><topic>Vascularization</topic><topic>Wound Healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wei, Shikun</creatorcontrib><creatorcontrib>Xu, Pengcheng</creatorcontrib><creatorcontrib>Yao, Zexin</creatorcontrib><creatorcontrib>Cui, Xiao</creatorcontrib><creatorcontrib>Lei, Xiaoxuan</creatorcontrib><creatorcontrib>Li, Linlin</creatorcontrib><creatorcontrib>Dong, Yunqing</creatorcontrib><creatorcontrib>Zhu, Weidong</creatorcontrib><creatorcontrib>Guo, Rui</creatorcontrib><creatorcontrib>Cheng, Biao</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion 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Biomater</addtitle><date>2021-04-01</date><risdate>2021</risdate><volume>124</volume><spage>205</spage><epage>218</epage><pages>205-218</pages><issn>1742-7061</issn><issn>1878-7568</issn><eissn>1878-7568</eissn><abstract>Diabetic wound healing remains a major challenge due to its vulnerability to bacterial infection, as well as the less vascularization and prolonged inflammatory phase. In this study, we developed a hydrogel system for the treatment of chronic infected wounds, which can regulate inflammatory (through the use of antimicrobial peptides) and enhance collagen deposition and angiogenesis (through the addition of platelet-rich plasma (PRP)). Based on the formation of Schiff base linkage, the ODEX/HA-AMP/PRP hydrogel was prepared by mixing oxidized dextran (ODEX), antimicrobial peptide-modified hyaluronic acid (HA-AMP) and PRP under physiological conditions, which exhibited obvious inhibition zones against three pathogenic bacterial strains (E. coli, S. aureus and P. aeruginosa) and slow release ability of antimicrobials and growth factors. Moreover, CCK-8, live/dead fluorescent staining and scratch test confirmed that ODEX/HA-AMP/PRP hydrogel could facilitate the proliferation and migration of L929 fibroblast cells. More importantly, in vivo experiments further demonstrated that the prepared hydrogels could significantly improve wound healing in a diabetic mouse infection by regulating inflammation, accelerating collagen deposition and angiogenesis. In addition, prepared hydrogel showed a significant antibacterial activity against S. aureus and P. aeruginosa, inhibited pro-inflammatory factors (TNF-α, IL-1β and IL-6), enhanced anti-inflammatory factors (TGF-β1) and vascular endothelial growth factor (VEGF) production. The findings of this study suggested that the composite hydrogel with AMP and PRP controlled release ability could be used as a promising candidate for chronic wound healing and infection-related wound healing.
[Display omitted]</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>33524559</pmid><doi>10.1016/j.actbio.2021.01.046</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-7674-073X</orcidid></addata></record> |
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| ispartof | Acta biomaterialia, 2021-04, Vol.124, p.205-218 |
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| subjects | Angiogenesis Animals Antibacterial activity Antimicrobial agents Antimicrobial peptide Antimicrobial peptides Bacterial diseases Bacterial infections Cell migration Cell proliferation Cholecystokinin Chronic infection Collagen Controlled release Deposition Dextran Dextrans Diabetes Diabetes Mellitus Diabetic infected wound E coli Escherichia coli Fluorescence Growth factors Hyaluronic acid Hydrogel Hydrogels IL-1β Imines In vivo methods and tests Infections Inflammation Interleukin 6 Mice Peptides Platelet-Rich Plasma Platelet-rich plasma (PRP) Platelets Pore Forming Cytotoxic Proteins Scratch tests Staphylococcus aureus Transforming growth factor-b1 Tumor necrosis factor-α Vascular endothelial growth factor Vascular Endothelial Growth Factor A Vascularization Wound Healing |
| title | A composite hydrogel with co-delivery of antimicrobial peptides and platelet-rich plasma to enhance healing of infected wounds in diabetes |
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