Bacteriophage‐cocktail hydrogel dressing to prevent multiple bacterial infections and heal diabetic ulcers in mice
Bacteriophage (phage) has been reported to reduce the bacterial infection in delayed‐healing wounds and, as a result, aiding in the healing of said wounds. In this study we investigated whether the presence of phage itself could help repair delayed‐healing wounds in diabetic mice. Three strains of p...
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| Veröffentlicht in: | Journal of biomedical materials research. Part A 2024-11, Vol.112 (11), p.1846-1859 |
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| creator | Shiue, Sheng‐Jie Wu, Ming‐Shun Chiang, Yi‐Hsien Lin, Hsin‐Yi |
| description | Bacteriophage (phage) has been reported to reduce the bacterial infection in delayed‐healing wounds and, as a result, aiding in the healing of said wounds. In this study we investigated whether the presence of phage itself could help repair delayed‐healing wounds in diabetic mice. Three strains of phage that target Salmonella enterica, Escherichia coli, and Pseudomonas aeruginosa were used. To prevent the phage liquid from running off the wound, the mixture of phage (phage‐cocktail) was encapsulated in a porous hydrogel dressing made with three‐dimensional printing. The phage‐cocktail dressing was tested for its phage preservation and release efficacy, bacterial reduction, cytotoxicity with 3T3 fibroblast, and performance in repairing a sterile full‐thickness skin wound in diabetic mice. The phage‐cocktail dressing released 1.7%–5.7% of the phages embedded in 24 h, and reduced between 37%–79% of the surface bacteria compared with the blank dressing (p |
| doi_str_mv | 10.1002/jbm.a.37728 |
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In this study we investigated whether the presence of phage itself could help repair delayed‐healing wounds in diabetic mice. Three strains of phage that target Salmonella enterica, Escherichia coli, and Pseudomonas aeruginosa were used. To prevent the phage liquid from running off the wound, the mixture of phage (phage‐cocktail) was encapsulated in a porous hydrogel dressing made with three‐dimensional printing. The phage‐cocktail dressing was tested for its phage preservation and release efficacy, bacterial reduction, cytotoxicity with 3T3 fibroblast, and performance in repairing a sterile full‐thickness skin wound in diabetic mice. The phage‐cocktail dressing released 1.7%–5.7% of the phages embedded in 24 h, and reduced between 37%–79% of the surface bacteria compared with the blank dressing (p <.05). The phage‐cocktail dressing exhibited no sign of cytotoxicity after 3 days (p <.05). In vivo studies showed that 14 days after incision, the full‐thickness wound treated with a phage‐cocktail dressing had a higher wound healing ratio compared with the blank dressing and control (p <.01). Histological analysis showed that the structure of the skin layers in the group treated with phage‐cocktail dressing was restored in an orderly fashion. Compared with the blank dressing and control, the repaired tissue in the phage‐cocktail dressing group had new capillary vessels and no sign of inflammation in its dermis, and its epidermis had a higher degree of re‐epithelialization (p <.05). The slow‐released phage has demonstrated positive effects in repairing diabetic skin wounds.</description><identifier>ISSN: 1549-3296</identifier><identifier>ISSN: 1552-4965</identifier><identifier>EISSN: 1552-4965</identifier><identifier>DOI: 10.1002/jbm.a.37728</identifier><identifier>PMID: 38706446</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>alginate hydrogel ; Animals ; antibacterial wound dressing ; Bacteria ; Bacterial diseases ; Bacterial Infections - prevention & control ; Bacterial Infections - therapy ; bacteriophage cocktail ; Bacteriophages ; Bandages ; Biocompatibility ; Cytotoxicity ; Dermis ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus, Experimental - complications ; Diabetes Mellitus, Experimental - therapy ; diabetic wound healing ; E coli ; Epidermis ; Hydrogels ; Hydrogels - chemistry ; In vivo methods and tests ; Male ; Mice ; Phages ; Plantar ulcers ; Skin ; Thickness ; three‐dimensional (3D) printing ; Toxicity testing ; Ulcers ; Wound Healing ; Wound infection</subject><ispartof>Journal of biomedical materials research. 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Part A</title><addtitle>J Biomed Mater Res A</addtitle><description>Bacteriophage (phage) has been reported to reduce the bacterial infection in delayed‐healing wounds and, as a result, aiding in the healing of said wounds. In this study we investigated whether the presence of phage itself could help repair delayed‐healing wounds in diabetic mice. Three strains of phage that target Salmonella enterica, Escherichia coli, and Pseudomonas aeruginosa were used. To prevent the phage liquid from running off the wound, the mixture of phage (phage‐cocktail) was encapsulated in a porous hydrogel dressing made with three‐dimensional printing. The phage‐cocktail dressing was tested for its phage preservation and release efficacy, bacterial reduction, cytotoxicity with 3T3 fibroblast, and performance in repairing a sterile full‐thickness skin wound in diabetic mice. The phage‐cocktail dressing released 1.7%–5.7% of the phages embedded in 24 h, and reduced between 37%–79% of the surface bacteria compared with the blank dressing (p <.05). The phage‐cocktail dressing exhibited no sign of cytotoxicity after 3 days (p <.05). In vivo studies showed that 14 days after incision, the full‐thickness wound treated with a phage‐cocktail dressing had a higher wound healing ratio compared with the blank dressing and control (p <.01). Histological analysis showed that the structure of the skin layers in the group treated with phage‐cocktail dressing was restored in an orderly fashion. Compared with the blank dressing and control, the repaired tissue in the phage‐cocktail dressing group had new capillary vessels and no sign of inflammation in its dermis, and its epidermis had a higher degree of re‐epithelialization (p <.05). The slow‐released phage has demonstrated positive effects in repairing diabetic skin wounds.</description><subject>alginate hydrogel</subject><subject>Animals</subject><subject>antibacterial wound dressing</subject><subject>Bacteria</subject><subject>Bacterial diseases</subject><subject>Bacterial Infections - prevention & control</subject><subject>Bacterial Infections - therapy</subject><subject>bacteriophage cocktail</subject><subject>Bacteriophages</subject><subject>Bandages</subject><subject>Biocompatibility</subject><subject>Cytotoxicity</subject><subject>Dermis</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus, Experimental - complications</subject><subject>Diabetes Mellitus, Experimental - therapy</subject><subject>diabetic wound healing</subject><subject>E coli</subject><subject>Epidermis</subject><subject>Hydrogels</subject><subject>Hydrogels - chemistry</subject><subject>In vivo methods and tests</subject><subject>Male</subject><subject>Mice</subject><subject>Phages</subject><subject>Plantar ulcers</subject><subject>Skin</subject><subject>Thickness</subject><subject>three‐dimensional (3D) printing</subject><subject>Toxicity testing</subject><subject>Ulcers</subject><subject>Wound Healing</subject><subject>Wound infection</subject><issn>1549-3296</issn><issn>1552-4965</issn><issn>1552-4965</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90b9u1TAUBnALUdFSmNiRJRakKhf_ieN4bCsKVEUsMFuOc3KvL04cbAd0Nx6hz9gnwSWFgYHJR9bPn478IfSCkg0lhL3Zd-PGbLiUrH2ETqgQrKpVIx7fz7WqOFPNMXqa0r7ghgj2BB3zVpKmrpsTlC-MzRBdmHdmC3c_b22wX7NxHu8OfQxb8LiPkJKbtjgHPEf4DlPG4-Kzmz3gbn1uPHbTADa7MCVsph7voNz1znSQncWLtxBTMXh0Fp6ho8H4BM8fzlP05ert58v31c2ndx8uz28qy2nbVpQ2PR0E63ppqaUGWquIrVsijWo5I8IwXg-1ldx0RBkhGmraoZPKMsOJsPwUvV5z5xi-LZCyHl2y4L2ZICxJF0RrJhVhhb76h-7DEqeyXVFK8UZyqYo6W5WNIaUIg56jG008aEr0fRm6lKGN_l1G0S8fMpduhP6v_fP7BbAV_HAeDv_L0tcXH8_X1F-QSJbe</recordid><startdate>202411</startdate><enddate>202411</enddate><creator>Shiue, Sheng‐Jie</creator><creator>Wu, Ming‐Shun</creator><creator>Chiang, Yi‐Hsien</creator><creator>Lin, Hsin‐Yi</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, 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>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</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/0000-0002-1401-1603</orcidid></search><sort><creationdate>202411</creationdate><title>Bacteriophage‐cocktail hydrogel dressing to prevent multiple bacterial infections and heal diabetic ulcers in mice</title><author>Shiue, Sheng‐Jie ; Wu, Ming‐Shun ; Chiang, Yi‐Hsien ; Lin, Hsin‐Yi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3188-116d1f52bd7c1c1ae8c90c4807a983205a234f4c73ab09a5561a8fb79c2a305c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>alginate hydrogel</topic><topic>Animals</topic><topic>antibacterial wound dressing</topic><topic>Bacteria</topic><topic>Bacterial diseases</topic><topic>Bacterial Infections - prevention & control</topic><topic>Bacterial Infections - therapy</topic><topic>bacteriophage cocktail</topic><topic>Bacteriophages</topic><topic>Bandages</topic><topic>Biocompatibility</topic><topic>Cytotoxicity</topic><topic>Dermis</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus, Experimental - complications</topic><topic>Diabetes Mellitus, Experimental - therapy</topic><topic>diabetic wound healing</topic><topic>E coli</topic><topic>Epidermis</topic><topic>Hydrogels</topic><topic>Hydrogels - chemistry</topic><topic>In vivo methods and tests</topic><topic>Male</topic><topic>Mice</topic><topic>Phages</topic><topic>Plantar ulcers</topic><topic>Skin</topic><topic>Thickness</topic><topic>three‐dimensional (3D) printing</topic><topic>Toxicity testing</topic><topic>Ulcers</topic><topic>Wound Healing</topic><topic>Wound infection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shiue, Sheng‐Jie</creatorcontrib><creatorcontrib>Wu, Ming‐Shun</creatorcontrib><creatorcontrib>Chiang, Yi‐Hsien</creatorcontrib><creatorcontrib>Lin, Hsin‐Yi</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 Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</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>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>ProQuest Health & Medical Complete (Alumni)</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>Journal of biomedical materials research. Part A</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shiue, Sheng‐Jie</au><au>Wu, Ming‐Shun</au><au>Chiang, Yi‐Hsien</au><au>Lin, Hsin‐Yi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bacteriophage‐cocktail hydrogel dressing to prevent multiple bacterial infections and heal diabetic ulcers in mice</atitle><jtitle>Journal of biomedical materials research. Part A</jtitle><addtitle>J Biomed Mater Res A</addtitle><date>2024-11</date><risdate>2024</risdate><volume>112</volume><issue>11</issue><spage>1846</spage><epage>1859</epage><pages>1846-1859</pages><issn>1549-3296</issn><issn>1552-4965</issn><eissn>1552-4965</eissn><abstract>Bacteriophage (phage) has been reported to reduce the bacterial infection in delayed‐healing wounds and, as a result, aiding in the healing of said wounds. In this study we investigated whether the presence of phage itself could help repair delayed‐healing wounds in diabetic mice. Three strains of phage that target Salmonella enterica, Escherichia coli, and Pseudomonas aeruginosa were used. To prevent the phage liquid from running off the wound, the mixture of phage (phage‐cocktail) was encapsulated in a porous hydrogel dressing made with three‐dimensional printing. The phage‐cocktail dressing was tested for its phage preservation and release efficacy, bacterial reduction, cytotoxicity with 3T3 fibroblast, and performance in repairing a sterile full‐thickness skin wound in diabetic mice. The phage‐cocktail dressing released 1.7%–5.7% of the phages embedded in 24 h, and reduced between 37%–79% of the surface bacteria compared with the blank dressing (p <.05). The phage‐cocktail dressing exhibited no sign of cytotoxicity after 3 days (p <.05). In vivo studies showed that 14 days after incision, the full‐thickness wound treated with a phage‐cocktail dressing had a higher wound healing ratio compared with the blank dressing and control (p <.01). Histological analysis showed that the structure of the skin layers in the group treated with phage‐cocktail dressing was restored in an orderly fashion. Compared with the blank dressing and control, the repaired tissue in the phage‐cocktail dressing group had new capillary vessels and no sign of inflammation in its dermis, and its epidermis had a higher degree of re‐epithelialization (p <.05). The slow‐released phage has demonstrated positive effects in repairing diabetic skin wounds.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>38706446</pmid><doi>10.1002/jbm.a.37728</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-1401-1603</orcidid></addata></record> |
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| subjects | alginate hydrogel Animals antibacterial wound dressing Bacteria Bacterial diseases Bacterial Infections - prevention & control Bacterial Infections - therapy bacteriophage cocktail Bacteriophages Bandages Biocompatibility Cytotoxicity Dermis Diabetes Diabetes mellitus Diabetes Mellitus, Experimental - complications Diabetes Mellitus, Experimental - therapy diabetic wound healing E coli Epidermis Hydrogels Hydrogels - chemistry In vivo methods and tests Male Mice Phages Plantar ulcers Skin Thickness three‐dimensional (3D) printing Toxicity testing Ulcers Wound Healing Wound infection |
| title | Bacteriophage‐cocktail hydrogel dressing to prevent multiple bacterial infections and heal diabetic ulcers in mice |
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