In vivo analysis of a first-in-class tri-alkyl norspermidine-biaryl antibiotic in an active release coating to reduce the risk of implant-related infection
[Display omitted] Prosthetic joint infection (PJI) is a well-known and persisting problem. Active release coatings have promise to provide early protection to an implant by eradicating small colony biofilm contaminants or planktonic bacteria that can form biofilm. Traditional antibiotics can be limi...
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| Veröffentlicht in: | Acta biomaterialia 2019-07, Vol.93, p.36-49 |
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| creator | Williams, Dustin L. Epperson, Richard T. Ashton, Nicholas N. Taylor, Nicholas B. Kawaguchi, Brooke Olsen, Raymond E. Haussener, Travis J. Sebahar, Paul R. Allyn, Gina Looper, Ryan E. |
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Prosthetic joint infection (PJI) is a well-known and persisting problem. Active release coatings have promise to provide early protection to an implant by eradicating small colony biofilm contaminants or planktonic bacteria that can form biofilm. Traditional antibiotics can be limited as active release agents in that they have limited effect against biofilms and develop resistance at sub-lethal concentrations. A unique first-in-class compound (CZ-01127) was assessed as the active release agent in a silicone (Si)-based coating to prevent PJI in a sheep model of joint space infection. Titanium (Ti) plugs contained a porous coated Ti (PCTi) region and polymer-coated region. Plugs were implanted into a femoral condyle of sheep to assess the effect of the Si polymer on cancellous bone ingrowth, the effect of CZ-01127 on bone ingrowth, and the ability of CZ-01127 to prevent PJI. Microbiological results showed that CZ-01127 was able to eradicate bacteria in the local region of the implanted plugs. Data further showed that Si did not adversely affect bone ingrowth. However, bacteria that reached the joint space (synovium) were not fully eradicated. Outcomes suggested that the CZ-01127 coating provided local protection to the implant system in a challenging model, the design of which could be beneficial for testing future antimicrobial therapies for PJI.
Periprosthetic joint infection (PJI) is now commonplace, and constitutes an underlying problem that patients and physicians face. Active release antibiotic coatings have potential to prevent these infections. Traditional antibiotics are limited in their ability to eradicate bacteria that reside in biofilms, and are more susceptible to resistance development. This study addressed these limitations by testing the efficacy of a unique antimicrobial compound in a coating that was tested in a challenging sheep model of PJI. The unique coating was able to eradicate bacteria and prevent infection in the environment adjacent to the implant. Bacteria that escaped into the joint space still caused infection, yet benchmark data can be used to optimize the coating and translate it toward clinical use. |
| doi_str_mv | 10.1016/j.actbio.2019.01.055 |
| format | Article |
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Prosthetic joint infection (PJI) is a well-known and persisting problem. Active release coatings have promise to provide early protection to an implant by eradicating small colony biofilm contaminants or planktonic bacteria that can form biofilm. Traditional antibiotics can be limited as active release agents in that they have limited effect against biofilms and develop resistance at sub-lethal concentrations. A unique first-in-class compound (CZ-01127) was assessed as the active release agent in a silicone (Si)-based coating to prevent PJI in a sheep model of joint space infection. Titanium (Ti) plugs contained a porous coated Ti (PCTi) region and polymer-coated region. Plugs were implanted into a femoral condyle of sheep to assess the effect of the Si polymer on cancellous bone ingrowth, the effect of CZ-01127 on bone ingrowth, and the ability of CZ-01127 to prevent PJI. Microbiological results showed that CZ-01127 was able to eradicate bacteria in the local region of the implanted plugs. Data further showed that Si did not adversely affect bone ingrowth. However, bacteria that reached the joint space (synovium) were not fully eradicated. Outcomes suggested that the CZ-01127 coating provided local protection to the implant system in a challenging model, the design of which could be beneficial for testing future antimicrobial therapies for PJI.
Periprosthetic joint infection (PJI) is now commonplace, and constitutes an underlying problem that patients and physicians face. Active release antibiotic coatings have potential to prevent these infections. Traditional antibiotics are limited in their ability to eradicate bacteria that reside in biofilms, and are more susceptible to resistance development. This study addressed these limitations by testing the efficacy of a unique antimicrobial compound in a coating that was tested in a challenging sheep model of PJI. The unique coating was able to eradicate bacteria and prevent infection in the environment adjacent to the implant. Bacteria that escaped into the joint space still caused infection, yet benchmark data can be used to optimize the coating and translate it toward clinical use.</description><identifier>ISSN: 1742-7061</identifier><identifier>EISSN: 1878-7568</identifier><identifier>DOI: 10.1016/j.actbio.2019.01.055</identifier><identifier>PMID: 30710710</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Antibiotics ; Bacteria ; Biofilms ; Bone ingrowth ; Cancellous bone ; Coating ; Coatings ; Contaminants ; CZ-01127 ; Drug delivery ; Femur ; Health risks ; Implant ; In vivo methods and tests ; Infections ; Joint diseases ; Joints (anatomy) ; Plugs ; Polymer coatings ; Polymers ; Prostheses ; Protective coatings ; Release agents ; Risk reduction ; Sheep ; Silicon ; Silicone ; Silicones ; Surgical implants ; Synovium ; Titanium</subject><ispartof>Acta biomaterialia, 2019-07, Vol.93, p.36-49</ispartof><rights>2019</rights><rights>Published by Elsevier Ltd.</rights><rights>Copyright Elsevier BV Jul 15, 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-d372d47f3f6c397e771da554b364794d43704aa7244f0a32453aac6a178aea263</citedby><cites>FETCH-LOGICAL-c390t-d372d47f3f6c397e771da554b364794d43704aa7244f0a32453aac6a178aea263</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1742706119300777$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30710710$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Williams, Dustin L.</creatorcontrib><creatorcontrib>Epperson, Richard T.</creatorcontrib><creatorcontrib>Ashton, Nicholas N.</creatorcontrib><creatorcontrib>Taylor, Nicholas B.</creatorcontrib><creatorcontrib>Kawaguchi, Brooke</creatorcontrib><creatorcontrib>Olsen, Raymond E.</creatorcontrib><creatorcontrib>Haussener, Travis J.</creatorcontrib><creatorcontrib>Sebahar, Paul R.</creatorcontrib><creatorcontrib>Allyn, Gina</creatorcontrib><creatorcontrib>Looper, Ryan E.</creatorcontrib><title>In vivo analysis of a first-in-class tri-alkyl norspermidine-biaryl antibiotic in an active release coating to reduce the risk of implant-related infection</title><title>Acta biomaterialia</title><addtitle>Acta Biomater</addtitle><description>[Display omitted]
Prosthetic joint infection (PJI) is a well-known and persisting problem. Active release coatings have promise to provide early protection to an implant by eradicating small colony biofilm contaminants or planktonic bacteria that can form biofilm. Traditional antibiotics can be limited as active release agents in that they have limited effect against biofilms and develop resistance at sub-lethal concentrations. A unique first-in-class compound (CZ-01127) was assessed as the active release agent in a silicone (Si)-based coating to prevent PJI in a sheep model of joint space infection. Titanium (Ti) plugs contained a porous coated Ti (PCTi) region and polymer-coated region. Plugs were implanted into a femoral condyle of sheep to assess the effect of the Si polymer on cancellous bone ingrowth, the effect of CZ-01127 on bone ingrowth, and the ability of CZ-01127 to prevent PJI. Microbiological results showed that CZ-01127 was able to eradicate bacteria in the local region of the implanted plugs. Data further showed that Si did not adversely affect bone ingrowth. However, bacteria that reached the joint space (synovium) were not fully eradicated. Outcomes suggested that the CZ-01127 coating provided local protection to the implant system in a challenging model, the design of which could be beneficial for testing future antimicrobial therapies for PJI.
Periprosthetic joint infection (PJI) is now commonplace, and constitutes an underlying problem that patients and physicians face. Active release antibiotic coatings have potential to prevent these infections. Traditional antibiotics are limited in their ability to eradicate bacteria that reside in biofilms, and are more susceptible to resistance development. This study addressed these limitations by testing the efficacy of a unique antimicrobial compound in a coating that was tested in a challenging sheep model of PJI. The unique coating was able to eradicate bacteria and prevent infection in the environment adjacent to the implant. Bacteria that escaped into the joint space still caused infection, yet benchmark data can be used to optimize the coating and translate it toward clinical use.</description><subject>Antibiotics</subject><subject>Bacteria</subject><subject>Biofilms</subject><subject>Bone ingrowth</subject><subject>Cancellous bone</subject><subject>Coating</subject><subject>Coatings</subject><subject>Contaminants</subject><subject>CZ-01127</subject><subject>Drug delivery</subject><subject>Femur</subject><subject>Health risks</subject><subject>Implant</subject><subject>In vivo methods and tests</subject><subject>Infections</subject><subject>Joint diseases</subject><subject>Joints (anatomy)</subject><subject>Plugs</subject><subject>Polymer coatings</subject><subject>Polymers</subject><subject>Prostheses</subject><subject>Protective coatings</subject><subject>Release agents</subject><subject>Risk reduction</subject><subject>Sheep</subject><subject>Silicon</subject><subject>Silicone</subject><subject>Silicones</subject><subject>Surgical implants</subject><subject>Synovium</subject><subject>Titanium</subject><issn>1742-7061</issn><issn>1878-7568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kc-KFDEQxhtR3HX1DUQCXrykTTrpTvdFkMU_Cwte9Bxq0tVas92dMUkP7LP4stYwqwcPQiBJ5Vdfiu-rqpda1Vrp7u2-hlB2FOtG6aFWulZt-6i61L3rpWu7_jGfnW2kU52-qJ7lvFfK9Lrpn1YXRjl9WpfVr5tVHOkYBaww32fKIk4CxEQpF0mrDDPkLEoiCfPd_SzWmPIB00IjrSh3BImLsBbiSQoFQSvfBE9GRxQJZ4SMIkQotH4XJXJp3AKK8oNfKd-dfqPlMLOCZBoKjiwxIffH9Xn1ZII544uH_ar69vHD1-vP8vbLp5vr97cymEEVORrXjNZNZuq44NA5PULb2p3prBvsaI1TFsA11k4KTGNbAxA60K4HhKYzV9Wbs-4hxZ8b5uIXygFnngrjln2jWcYNqjOMvv4H3cctsXVMNZ1zhtGBKXumQoo5J5z8IdHCVnmt_Ck8v_fn8PwpPK-05_C47dWD-LZbcPzb9CctBt6dAWQ3joTJ50C4BhwpsWV-jPT_H34D84muTg</recordid><startdate>20190715</startdate><enddate>20190715</enddate><creator>Williams, Dustin L.</creator><creator>Epperson, Richard T.</creator><creator>Ashton, Nicholas N.</creator><creator>Taylor, Nicholas B.</creator><creator>Kawaguchi, Brooke</creator><creator>Olsen, Raymond E.</creator><creator>Haussener, Travis J.</creator><creator>Sebahar, Paul R.</creator><creator>Allyn, Gina</creator><creator>Looper, Ryan E.</creator><general>Elsevier Ltd</general><general>Elsevier BV</general><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></search><sort><creationdate>20190715</creationdate><title>In vivo analysis of a first-in-class tri-alkyl norspermidine-biaryl antibiotic in an active release coating to reduce the risk of implant-related infection</title><author>Williams, Dustin L. ; Epperson, Richard T. ; Ashton, Nicholas N. ; Taylor, Nicholas B. ; Kawaguchi, Brooke ; Olsen, Raymond E. ; Haussener, Travis J. ; Sebahar, Paul R. ; Allyn, Gina ; Looper, Ryan E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-d372d47f3f6c397e771da554b364794d43704aa7244f0a32453aac6a178aea263</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Antibiotics</topic><topic>Bacteria</topic><topic>Biofilms</topic><topic>Bone ingrowth</topic><topic>Cancellous bone</topic><topic>Coating</topic><topic>Coatings</topic><topic>Contaminants</topic><topic>CZ-01127</topic><topic>Drug delivery</topic><topic>Femur</topic><topic>Health risks</topic><topic>Implant</topic><topic>In vivo methods and tests</topic><topic>Infections</topic><topic>Joint diseases</topic><topic>Joints (anatomy)</topic><topic>Plugs</topic><topic>Polymer coatings</topic><topic>Polymers</topic><topic>Prostheses</topic><topic>Protective coatings</topic><topic>Release agents</topic><topic>Risk reduction</topic><topic>Sheep</topic><topic>Silicon</topic><topic>Silicone</topic><topic>Silicones</topic><topic>Surgical implants</topic><topic>Synovium</topic><topic>Titanium</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Williams, Dustin L.</creatorcontrib><creatorcontrib>Epperson, Richard T.</creatorcontrib><creatorcontrib>Ashton, Nicholas N.</creatorcontrib><creatorcontrib>Taylor, Nicholas B.</creatorcontrib><creatorcontrib>Kawaguchi, Brooke</creatorcontrib><creatorcontrib>Olsen, Raymond E.</creatorcontrib><creatorcontrib>Haussener, Travis J.</creatorcontrib><creatorcontrib>Sebahar, Paul R.</creatorcontrib><creatorcontrib>Allyn, Gina</creatorcontrib><creatorcontrib>Looper, Ryan E.</creatorcontrib><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 Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Acta biomaterialia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Williams, Dustin L.</au><au>Epperson, Richard T.</au><au>Ashton, Nicholas N.</au><au>Taylor, Nicholas B.</au><au>Kawaguchi, Brooke</au><au>Olsen, Raymond E.</au><au>Haussener, Travis J.</au><au>Sebahar, Paul R.</au><au>Allyn, Gina</au><au>Looper, Ryan E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vivo analysis of a first-in-class tri-alkyl norspermidine-biaryl antibiotic in an active release coating to reduce the risk of implant-related infection</atitle><jtitle>Acta biomaterialia</jtitle><addtitle>Acta Biomater</addtitle><date>2019-07-15</date><risdate>2019</risdate><volume>93</volume><spage>36</spage><epage>49</epage><pages>36-49</pages><issn>1742-7061</issn><eissn>1878-7568</eissn><abstract>[Display omitted]
Prosthetic joint infection (PJI) is a well-known and persisting problem. Active release coatings have promise to provide early protection to an implant by eradicating small colony biofilm contaminants or planktonic bacteria that can form biofilm. Traditional antibiotics can be limited as active release agents in that they have limited effect against biofilms and develop resistance at sub-lethal concentrations. A unique first-in-class compound (CZ-01127) was assessed as the active release agent in a silicone (Si)-based coating to prevent PJI in a sheep model of joint space infection. Titanium (Ti) plugs contained a porous coated Ti (PCTi) region and polymer-coated region. Plugs were implanted into a femoral condyle of sheep to assess the effect of the Si polymer on cancellous bone ingrowth, the effect of CZ-01127 on bone ingrowth, and the ability of CZ-01127 to prevent PJI. Microbiological results showed that CZ-01127 was able to eradicate bacteria in the local region of the implanted plugs. Data further showed that Si did not adversely affect bone ingrowth. However, bacteria that reached the joint space (synovium) were not fully eradicated. Outcomes suggested that the CZ-01127 coating provided local protection to the implant system in a challenging model, the design of which could be beneficial for testing future antimicrobial therapies for PJI.
Periprosthetic joint infection (PJI) is now commonplace, and constitutes an underlying problem that patients and physicians face. Active release antibiotic coatings have potential to prevent these infections. Traditional antibiotics are limited in their ability to eradicate bacteria that reside in biofilms, and are more susceptible to resistance development. This study addressed these limitations by testing the efficacy of a unique antimicrobial compound in a coating that was tested in a challenging sheep model of PJI. The unique coating was able to eradicate bacteria and prevent infection in the environment adjacent to the implant. Bacteria that escaped into the joint space still caused infection, yet benchmark data can be used to optimize the coating and translate it toward clinical use.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>30710710</pmid><doi>10.1016/j.actbio.2019.01.055</doi><tpages>14</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Acta biomaterialia, 2019-07, Vol.93, p.36-49 |
| issn | 1742-7061 1878-7568 |
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| source | Elsevier ScienceDirect Journals |
| subjects | Antibiotics Bacteria Biofilms Bone ingrowth Cancellous bone Coating Coatings Contaminants CZ-01127 Drug delivery Femur Health risks Implant In vivo methods and tests Infections Joint diseases Joints (anatomy) Plugs Polymer coatings Polymers Prostheses Protective coatings Release agents Risk reduction Sheep Silicon Silicone Silicones Surgical implants Synovium Titanium |
| title | In vivo analysis of a first-in-class tri-alkyl norspermidine-biaryl antibiotic in an active release coating to reduce the risk of implant-related infection |
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