Minocycline enhances the mesenchymal stromal/stem cell pro-healing phenotype in triple antimicrobial-loaded hydrogels
[Display omitted] Mesenchymal stromal/stem cells (MSCs) have demonstrated pro-healing properties including an anti-inflammatory cytokine profile and the promotion of angiogenesis via expression of growth factors in pre-clinical models. MSCs encapsulated in poly(ethylene glycol) diacrylate (PEGdA) an...
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| Veröffentlicht in: | Acta biomaterialia 2017-03, Vol.51, p.184-196 |
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| creator | Guerra, Alberto Daniel Rose, Warren E. Hematti, Peiman Kao, W. John |
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Mesenchymal stromal/stem cells (MSCs) have demonstrated pro-healing properties including an anti-inflammatory cytokine profile and the promotion of angiogenesis via expression of growth factors in pre-clinical models. MSCs encapsulated in poly(ethylene glycol) diacrylate (PEGdA) and thiolated gelatin poly(ethylene glycol) (Gel-PEG-Cys) crosslinked hydrogels have led to controlled cellular presentation at wound sites with favorable wound healing outcomes. However, the therapeutic potential of MSC-loaded hydrogels may be limited by non-specific protein adsorption on the delivery matrix that could facilitate the initial adhesion of microorganisms and subsequent virulent biofilm formation. Antimicrobials loaded concurrently in the hydrogels with MSCs could reduce microbial bioburden and promote healing, but the antimicrobial effect on the MSC wound healing capacity and the antibacterial efficacy of the hydrogels is unknown. We demonstrate that minocycline specifically induces a favorable change in MSC migration capacity, proliferation, gene expression, extracellular matrix (ECM) attachment, and adhesion molecule and growth factor release with subsequent increased angiogenesis. We then demonstrate that hydrogels loaded with MSCs, minocycline, vancomycin, and linezolid can significantly decrease bacterial bioburden. Our study suggests that minocycline can serve as a dual mechanism for the regenerative capacity of MSCs and the reduction of bioburden in triple antimicrobial-loaded hydrogels.
Wound healing is a complex biological process that can be hindered by bacterial infection, excessive inflammation, and inadequate microvasculature. In this study, we develop a new formulation of poly(ethylene glycol) diacrylate and thiolated gelatin poly(ethylene glycol) crosslinked hydrogels loaded with minocycline, vancomycin, linezolid, and mesenchymal stromal/stem cells that induces a favorable wound healing phenotype in mesenchymal stromal/stem cells and prevents bacterial bioburden on the hydrogel. This combinatorial approach to biomaterial development has the potential to impact wound healing for contaminated full thickness cutaneous wounds. |
| doi_str_mv | 10.1016/j.actbio.2017.01.021 |
| format | Article |
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Mesenchymal stromal/stem cells (MSCs) have demonstrated pro-healing properties including an anti-inflammatory cytokine profile and the promotion of angiogenesis via expression of growth factors in pre-clinical models. MSCs encapsulated in poly(ethylene glycol) diacrylate (PEGdA) and thiolated gelatin poly(ethylene glycol) (Gel-PEG-Cys) crosslinked hydrogels have led to controlled cellular presentation at wound sites with favorable wound healing outcomes. However, the therapeutic potential of MSC-loaded hydrogels may be limited by non-specific protein adsorption on the delivery matrix that could facilitate the initial adhesion of microorganisms and subsequent virulent biofilm formation. Antimicrobials loaded concurrently in the hydrogels with MSCs could reduce microbial bioburden and promote healing, but the antimicrobial effect on the MSC wound healing capacity and the antibacterial efficacy of the hydrogels is unknown. We demonstrate that minocycline specifically induces a favorable change in MSC migration capacity, proliferation, gene expression, extracellular matrix (ECM) attachment, and adhesion molecule and growth factor release with subsequent increased angiogenesis. We then demonstrate that hydrogels loaded with MSCs, minocycline, vancomycin, and linezolid can significantly decrease bacterial bioburden. Our study suggests that minocycline can serve as a dual mechanism for the regenerative capacity of MSCs and the reduction of bioburden in triple antimicrobial-loaded hydrogels.
Wound healing is a complex biological process that can be hindered by bacterial infection, excessive inflammation, and inadequate microvasculature. In this study, we develop a new formulation of poly(ethylene glycol) diacrylate and thiolated gelatin poly(ethylene glycol) crosslinked hydrogels loaded with minocycline, vancomycin, linezolid, and mesenchymal stromal/stem cells that induces a favorable wound healing phenotype in mesenchymal stromal/stem cells and prevents bacterial bioburden on the hydrogel. This combinatorial approach to biomaterial development has the potential to impact wound healing for contaminated full thickness cutaneous wounds.</description><identifier>ISSN: 1742-7061</identifier><identifier>EISSN: 1878-7568</identifier><identifier>DOI: 10.1016/j.actbio.2017.01.021</identifier><identifier>PMID: 28069512</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adhesion ; Adult ; Angiogenesis ; Anti-Infective Agents - pharmacology ; Antiinfectives and antibacterials ; Antimicrobial agents ; Bacteria ; Bacterial Adhesion - drug effects ; Biofilms ; Cell Adhesion - drug effects ; Cell Survival - drug effects ; Crosslinking ; Extracellular matrix ; Gelatin ; Gene expression ; Genotype & phenotype ; Growth factors ; Human Umbilical Vein Endothelial Cells - drug effects ; Humans ; Hydrogel ; Hydrogels ; Hydrogels - pharmacology ; Immunomodulation - drug effects ; Inflammation ; Intercellular Signaling Peptides and Proteins - pharmacology ; Linezolid ; Mesenchymal Stem Cells - cytology ; Mesenchymal Stem Cells - drug effects ; Mesenchymal stromal/stem cells ; Mesenchyme ; Microbial Sensitivity Tests ; Microorganisms ; Minocycline ; Minocycline - pharmacology ; Neovascularization, Physiologic - drug effects ; Phenotype ; Polyethylene glycol ; Protein adsorption ; Staphylococcus aureus ; Staphylococcus aureus - drug effects ; Staphylococcus aureus - growth & development ; Stem cells ; Vancomycin ; Wound healing ; Wound Healing - drug effects</subject><ispartof>Acta biomaterialia, 2017-03, Vol.51, p.184-196</ispartof><rights>2017</rights><rights>Copyright © 2017. Published by Elsevier Ltd.</rights><rights>Copyright Elsevier BV Mar 15, 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c528t-5e4146687ae83231a5c56e2c7621cfd88b5a4fc69c43afadce5ad883c735994c3</citedby><cites>FETCH-LOGICAL-c528t-5e4146687ae83231a5c56e2c7621cfd88b5a4fc69c43afadce5ad883c735994c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.actbio.2017.01.021$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28069512$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Guerra, Alberto Daniel</creatorcontrib><creatorcontrib>Rose, Warren E.</creatorcontrib><creatorcontrib>Hematti, Peiman</creatorcontrib><creatorcontrib>Kao, W. John</creatorcontrib><title>Minocycline enhances the mesenchymal stromal/stem cell pro-healing phenotype in triple antimicrobial-loaded hydrogels</title><title>Acta biomaterialia</title><addtitle>Acta Biomater</addtitle><description>[Display omitted]
Mesenchymal stromal/stem cells (MSCs) have demonstrated pro-healing properties including an anti-inflammatory cytokine profile and the promotion of angiogenesis via expression of growth factors in pre-clinical models. MSCs encapsulated in poly(ethylene glycol) diacrylate (PEGdA) and thiolated gelatin poly(ethylene glycol) (Gel-PEG-Cys) crosslinked hydrogels have led to controlled cellular presentation at wound sites with favorable wound healing outcomes. However, the therapeutic potential of MSC-loaded hydrogels may be limited by non-specific protein adsorption on the delivery matrix that could facilitate the initial adhesion of microorganisms and subsequent virulent biofilm formation. Antimicrobials loaded concurrently in the hydrogels with MSCs could reduce microbial bioburden and promote healing, but the antimicrobial effect on the MSC wound healing capacity and the antibacterial efficacy of the hydrogels is unknown. We demonstrate that minocycline specifically induces a favorable change in MSC migration capacity, proliferation, gene expression, extracellular matrix (ECM) attachment, and adhesion molecule and growth factor release with subsequent increased angiogenesis. We then demonstrate that hydrogels loaded with MSCs, minocycline, vancomycin, and linezolid can significantly decrease bacterial bioburden. Our study suggests that minocycline can serve as a dual mechanism for the regenerative capacity of MSCs and the reduction of bioburden in triple antimicrobial-loaded hydrogels.
Wound healing is a complex biological process that can be hindered by bacterial infection, excessive inflammation, and inadequate microvasculature. In this study, we develop a new formulation of poly(ethylene glycol) diacrylate and thiolated gelatin poly(ethylene glycol) crosslinked hydrogels loaded with minocycline, vancomycin, linezolid, and mesenchymal stromal/stem cells that induces a favorable wound healing phenotype in mesenchymal stromal/stem cells and prevents bacterial bioburden on the hydrogel. This combinatorial approach to biomaterial development has the potential to impact wound healing for contaminated full thickness cutaneous wounds.</description><subject>Adhesion</subject><subject>Adult</subject><subject>Angiogenesis</subject><subject>Anti-Infective Agents - pharmacology</subject><subject>Antiinfectives and antibacterials</subject><subject>Antimicrobial agents</subject><subject>Bacteria</subject><subject>Bacterial Adhesion - drug effects</subject><subject>Biofilms</subject><subject>Cell Adhesion - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Crosslinking</subject><subject>Extracellular matrix</subject><subject>Gelatin</subject><subject>Gene expression</subject><subject>Genotype & phenotype</subject><subject>Growth factors</subject><subject>Human Umbilical Vein Endothelial Cells - drug effects</subject><subject>Humans</subject><subject>Hydrogel</subject><subject>Hydrogels</subject><subject>Hydrogels - pharmacology</subject><subject>Immunomodulation - drug effects</subject><subject>Inflammation</subject><subject>Intercellular Signaling Peptides and Proteins - pharmacology</subject><subject>Linezolid</subject><subject>Mesenchymal Stem Cells - cytology</subject><subject>Mesenchymal Stem Cells - drug effects</subject><subject>Mesenchymal stromal/stem cells</subject><subject>Mesenchyme</subject><subject>Microbial Sensitivity Tests</subject><subject>Microorganisms</subject><subject>Minocycline</subject><subject>Minocycline - pharmacology</subject><subject>Neovascularization, Physiologic - drug effects</subject><subject>Phenotype</subject><subject>Polyethylene glycol</subject><subject>Protein adsorption</subject><subject>Staphylococcus aureus</subject><subject>Staphylococcus aureus - drug effects</subject><subject>Staphylococcus aureus - growth & development</subject><subject>Stem cells</subject><subject>Vancomycin</subject><subject>Wound healing</subject><subject>Wound Healing - drug effects</subject><issn>1742-7061</issn><issn>1878-7568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UcuO1DAQjBCIXRb-ACFLXLgk60f8mAsSWvGSFnGBs-VxOhOPHDvYzkr5ezyaZXkcOLXlrq7uqmqalwR3BBNxfeyMLXsXO4qJ7DDpMCWPmkuipGolF-pxfcuethILctE8y_mIMVOEqqfNBVVY7Dihl836xYVoN-tdAARhMsFCRmUCNEOGYKdtNh7lkmKt17nAjCx4j5YU2wlMHTugZYIQy7YAcgGV5BYPyITiZmdT3DvjWx_NAAOatiHFA_j8vHkyGp_hxX29ar5_eP_t5lN7-_Xj55t3t63lVJWWQ096IZQ0oBhlxHDLBVArBSV2HJTac9OPVuxsz8xoBgvc1F9mJeO7XW_ZVfP2zLus-xlqP5RkvF6Sm03adDRO_90JbtKHeKe5xP1OsErw5p4gxR8r5KJnl08GmABxzZooLpmsR9IKff0P9BjXFKo8TU5UVQAjFdWfUdWanBOMD8cQrE-56qM-56pPuWpMdM21jr36U8jD0K8gfyut7sKdg6SzdTU_GFwCW_QQ3f83_AS3_bla</recordid><startdate>20170315</startdate><enddate>20170315</enddate><creator>Guerra, Alberto Daniel</creator><creator>Rose, Warren E.</creator><creator>Hematti, Peiman</creator><creator>Kao, W. 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John</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c528t-5e4146687ae83231a5c56e2c7621cfd88b5a4fc69c43afadce5ad883c735994c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adhesion</topic><topic>Adult</topic><topic>Angiogenesis</topic><topic>Anti-Infective Agents - pharmacology</topic><topic>Antiinfectives and antibacterials</topic><topic>Antimicrobial agents</topic><topic>Bacteria</topic><topic>Bacterial Adhesion - drug effects</topic><topic>Biofilms</topic><topic>Cell Adhesion - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Crosslinking</topic><topic>Extracellular matrix</topic><topic>Gelatin</topic><topic>Gene expression</topic><topic>Genotype & phenotype</topic><topic>Growth factors</topic><topic>Human Umbilical Vein Endothelial Cells - drug effects</topic><topic>Humans</topic><topic>Hydrogel</topic><topic>Hydrogels</topic><topic>Hydrogels - pharmacology</topic><topic>Immunomodulation - drug effects</topic><topic>Inflammation</topic><topic>Intercellular Signaling Peptides and Proteins - pharmacology</topic><topic>Linezolid</topic><topic>Mesenchymal Stem Cells - cytology</topic><topic>Mesenchymal Stem Cells - drug effects</topic><topic>Mesenchymal stromal/stem cells</topic><topic>Mesenchyme</topic><topic>Microbial Sensitivity Tests</topic><topic>Microorganisms</topic><topic>Minocycline</topic><topic>Minocycline - pharmacology</topic><topic>Neovascularization, Physiologic - drug effects</topic><topic>Phenotype</topic><topic>Polyethylene glycol</topic><topic>Protein adsorption</topic><topic>Staphylococcus aureus</topic><topic>Staphylococcus aureus - drug effects</topic><topic>Staphylococcus aureus - growth & development</topic><topic>Stem cells</topic><topic>Vancomycin</topic><topic>Wound healing</topic><topic>Wound Healing - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guerra, Alberto Daniel</creatorcontrib><creatorcontrib>Rose, Warren E.</creatorcontrib><creatorcontrib>Hematti, Peiman</creatorcontrib><creatorcontrib>Kao, W. 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John</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Minocycline enhances the mesenchymal stromal/stem cell pro-healing phenotype in triple antimicrobial-loaded hydrogels</atitle><jtitle>Acta biomaterialia</jtitle><addtitle>Acta Biomater</addtitle><date>2017-03-15</date><risdate>2017</risdate><volume>51</volume><spage>184</spage><epage>196</epage><pages>184-196</pages><issn>1742-7061</issn><eissn>1878-7568</eissn><abstract>[Display omitted]
Mesenchymal stromal/stem cells (MSCs) have demonstrated pro-healing properties including an anti-inflammatory cytokine profile and the promotion of angiogenesis via expression of growth factors in pre-clinical models. MSCs encapsulated in poly(ethylene glycol) diacrylate (PEGdA) and thiolated gelatin poly(ethylene glycol) (Gel-PEG-Cys) crosslinked hydrogels have led to controlled cellular presentation at wound sites with favorable wound healing outcomes. However, the therapeutic potential of MSC-loaded hydrogels may be limited by non-specific protein adsorption on the delivery matrix that could facilitate the initial adhesion of microorganisms and subsequent virulent biofilm formation. Antimicrobials loaded concurrently in the hydrogels with MSCs could reduce microbial bioburden and promote healing, but the antimicrobial effect on the MSC wound healing capacity and the antibacterial efficacy of the hydrogels is unknown. We demonstrate that minocycline specifically induces a favorable change in MSC migration capacity, proliferation, gene expression, extracellular matrix (ECM) attachment, and adhesion molecule and growth factor release with subsequent increased angiogenesis. We then demonstrate that hydrogels loaded with MSCs, minocycline, vancomycin, and linezolid can significantly decrease bacterial bioburden. Our study suggests that minocycline can serve as a dual mechanism for the regenerative capacity of MSCs and the reduction of bioburden in triple antimicrobial-loaded hydrogels.
Wound healing is a complex biological process that can be hindered by bacterial infection, excessive inflammation, and inadequate microvasculature. In this study, we develop a new formulation of poly(ethylene glycol) diacrylate and thiolated gelatin poly(ethylene glycol) crosslinked hydrogels loaded with minocycline, vancomycin, linezolid, and mesenchymal stromal/stem cells that induces a favorable wound healing phenotype in mesenchymal stromal/stem cells and prevents bacterial bioburden on the hydrogel. This combinatorial approach to biomaterial development has the potential to impact wound healing for contaminated full thickness cutaneous wounds.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>28069512</pmid><doi>10.1016/j.actbio.2017.01.021</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adhesion Adult Angiogenesis Anti-Infective Agents - pharmacology Antiinfectives and antibacterials Antimicrobial agents Bacteria Bacterial Adhesion - drug effects Biofilms Cell Adhesion - drug effects Cell Survival - drug effects Crosslinking Extracellular matrix Gelatin Gene expression Genotype & phenotype Growth factors Human Umbilical Vein Endothelial Cells - drug effects Humans Hydrogel Hydrogels Hydrogels - pharmacology Immunomodulation - drug effects Inflammation Intercellular Signaling Peptides and Proteins - pharmacology Linezolid Mesenchymal Stem Cells - cytology Mesenchymal Stem Cells - drug effects Mesenchymal stromal/stem cells Mesenchyme Microbial Sensitivity Tests Microorganisms Minocycline Minocycline - pharmacology Neovascularization, Physiologic - drug effects Phenotype Polyethylene glycol Protein adsorption Staphylococcus aureus Staphylococcus aureus - drug effects Staphylococcus aureus - growth & development Stem cells Vancomycin Wound healing Wound Healing - drug effects |
| title | Minocycline enhances the mesenchymal stromal/stem cell pro-healing phenotype in triple antimicrobial-loaded hydrogels |
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