Layer-by-Layer Microneedle-Mediated rhEGF Transdermal Delivery for Enhanced Wound Epidermal Regeneration and Angiogenesis
Appropriate treatments for acute traumas tend to avoid hemorrhages, vascular damage, and infections. However, in the homeostasis-imbalanced wound microenvironment, currently developed therapies could not precisely and controllably deliver biomacromolecular drugs, which are confronted with challenges...
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Veröffentlicht in: | ACS applied materials & interfaces 2023-05, Vol.15 (18), p.21929-21940 |
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creator | Yuan, Renqiang Yang, Ning Huang, Yueru Li, Weikun Zeng, Yi Liu, Zonghao Tan, Xin Feng, Fang Zhang, Qianli Su, Shao Chu, Cuilin Liu, Ling Ge, Liqin |
description | Appropriate treatments for acute traumas tend to avoid hemorrhages, vascular damage, and infections. However, in the homeostasis-imbalanced wound microenvironment, currently developed therapies could not precisely and controllably deliver biomacromolecular drugs, which are confronted with challenges due to large molecular weight, poor biomembrane permeability, low dosage, rapid degradation, and bioactivity loss. To conquer this, we construct a simple and effective layer-by-layer (LBL) self-assembly transdermal delivery patch, bearing microneedles (MN) coated with recombinant human epidermal growth factor (LBL MN-rhEGF) for a sustained release to wound bed driven by typical electrostatic force. Pyramidal LBL MN-rhEGF patches hold so enough mechanical strength to penetrate the stratum corneum, and generated microchannels allow rhEGF direct delivery in situ. The administrable delivery of biomacromolecular rhEGF through hierarchically coated MN arrays follows the diffusion mechanism of Fick’s second law. Numerous efforts further have illustrated that finger-pressing LBL MN-rhEGF patches could not only promote cell proliferation of normal human dermal fibroblasts (NHDF) and human umbilical vein endothelial cells (HUVEC) in vitro but also take significant effects (regenerative epidermis: ∼144 μm; pro-angiogenesis: higher CD31 expression) in accelerating wound healing of mechanically injured rats, compared to the traditional dressing, which relies on passive diffusion. Our proof-of-concept features novel LBL biomacromolecular drug-delivery systems and self-administrated precision medicine modes at the point of care. |
doi_str_mv | 10.1021/acsami.3c02254 |
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However, in the homeostasis-imbalanced wound microenvironment, currently developed therapies could not precisely and controllably deliver biomacromolecular drugs, which are confronted with challenges due to large molecular weight, poor biomembrane permeability, low dosage, rapid degradation, and bioactivity loss. To conquer this, we construct a simple and effective layer-by-layer (LBL) self-assembly transdermal delivery patch, bearing microneedles (MN) coated with recombinant human epidermal growth factor (LBL MN-rhEGF) for a sustained release to wound bed driven by typical electrostatic force. Pyramidal LBL MN-rhEGF patches hold so enough mechanical strength to penetrate the stratum corneum, and generated microchannels allow rhEGF direct delivery in situ. The administrable delivery of biomacromolecular rhEGF through hierarchically coated MN arrays follows the diffusion mechanism of Fick’s second law. Numerous efforts further have illustrated that finger-pressing LBL MN-rhEGF patches could not only promote cell proliferation of normal human dermal fibroblasts (NHDF) and human umbilical vein endothelial cells (HUVEC) in vitro but also take significant effects (regenerative epidermis: ∼144 μm; pro-angiogenesis: higher CD31 expression) in accelerating wound healing of mechanically injured rats, compared to the traditional dressing, which relies on passive diffusion. Our proof-of-concept features novel LBL biomacromolecular drug-delivery systems and self-administrated precision medicine modes at the point of care.</description><identifier>ISSN: 1944-8244</identifier><identifier>EISSN: 1944-8252</identifier><identifier>DOI: 10.1021/acsami.3c02254</identifier><identifier>PMID: 37126734</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Animals ; Biological and Medical Applications of Materials and Interfaces ; Cell Proliferation ; Endothelial Cells - metabolism ; Epidermal Growth Factor - metabolism ; Epidermis - metabolism ; Humans ; Rats ; Recombinant Proteins ; Wound Healing</subject><ispartof>ACS applied materials & interfaces, 2023-05, Vol.15 (18), p.21929-21940</ispartof><rights>2023 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0001-9622-3732 ; 0000-0002-9399-8249</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acsami.3c02254$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acsami.3c02254$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37126734$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yuan, Renqiang</creatorcontrib><creatorcontrib>Yang, Ning</creatorcontrib><creatorcontrib>Huang, Yueru</creatorcontrib><creatorcontrib>Li, Weikun</creatorcontrib><creatorcontrib>Zeng, Yi</creatorcontrib><creatorcontrib>Liu, Zonghao</creatorcontrib><creatorcontrib>Tan, Xin</creatorcontrib><creatorcontrib>Feng, Fang</creatorcontrib><creatorcontrib>Zhang, Qianli</creatorcontrib><creatorcontrib>Su, Shao</creatorcontrib><creatorcontrib>Chu, Cuilin</creatorcontrib><creatorcontrib>Liu, Ling</creatorcontrib><creatorcontrib>Ge, Liqin</creatorcontrib><title>Layer-by-Layer Microneedle-Mediated rhEGF Transdermal Delivery for Enhanced Wound Epidermal Regeneration and Angiogenesis</title><title>ACS applied materials & interfaces</title><addtitle>ACS Appl. Mater. Interfaces</addtitle><description>Appropriate treatments for acute traumas tend to avoid hemorrhages, vascular damage, and infections. However, in the homeostasis-imbalanced wound microenvironment, currently developed therapies could not precisely and controllably deliver biomacromolecular drugs, which are confronted with challenges due to large molecular weight, poor biomembrane permeability, low dosage, rapid degradation, and bioactivity loss. To conquer this, we construct a simple and effective layer-by-layer (LBL) self-assembly transdermal delivery patch, bearing microneedles (MN) coated with recombinant human epidermal growth factor (LBL MN-rhEGF) for a sustained release to wound bed driven by typical electrostatic force. Pyramidal LBL MN-rhEGF patches hold so enough mechanical strength to penetrate the stratum corneum, and generated microchannels allow rhEGF direct delivery in situ. The administrable delivery of biomacromolecular rhEGF through hierarchically coated MN arrays follows the diffusion mechanism of Fick’s second law. Numerous efforts further have illustrated that finger-pressing LBL MN-rhEGF patches could not only promote cell proliferation of normal human dermal fibroblasts (NHDF) and human umbilical vein endothelial cells (HUVEC) in vitro but also take significant effects (regenerative epidermis: ∼144 μm; pro-angiogenesis: higher CD31 expression) in accelerating wound healing of mechanically injured rats, compared to the traditional dressing, which relies on passive diffusion. Our proof-of-concept features novel LBL biomacromolecular drug-delivery systems and self-administrated precision medicine modes at the point of care.</description><subject>Animals</subject><subject>Biological and Medical Applications of Materials and Interfaces</subject><subject>Cell Proliferation</subject><subject>Endothelial Cells - metabolism</subject><subject>Epidermal Growth Factor - metabolism</subject><subject>Epidermis - metabolism</subject><subject>Humans</subject><subject>Rats</subject><subject>Recombinant Proteins</subject><subject>Wound Healing</subject><issn>1944-8244</issn><issn>1944-8252</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kE1Lw0AQQBdRrFavHiVnIXU_m-yx1LQKLYJUPIbJ7qTdkmzKphXy701tlTnMMPMYZh4hD4yOGOXsGUwLtRsJQzlX8oLcMC1lnHLFL_9rKQfktm23lI4Fp-qaDETC-DgR8oZ0C-gwxEUX_xbR0pnQeERbYbxE62CPNgqbbD6LVgF8azHUUEUvWLlvDF1UNiHK_Aa86bmv5uBtlO3cmfrANXoMsHeNj6AfTfzaNcde69o7clVC1eL9OQ_J5yxbTV_jxfv8bTpZxMCk2MdGCYV9WF6CLJlOEpPKFFUpTKpLBYWi_eMCtLYgCsa0VbqgQMeSWmOFFkPyeNq7OxQ12nwXXA2hy_8c9MDTCehd5tvmEHx_Ts5ofhScnwTnZ8HiBzgIbj4</recordid><startdate>20230510</startdate><enddate>20230510</enddate><creator>Yuan, Renqiang</creator><creator>Yang, Ning</creator><creator>Huang, Yueru</creator><creator>Li, Weikun</creator><creator>Zeng, Yi</creator><creator>Liu, Zonghao</creator><creator>Tan, Xin</creator><creator>Feng, Fang</creator><creator>Zhang, Qianli</creator><creator>Su, Shao</creator><creator>Chu, Cuilin</creator><creator>Liu, Ling</creator><creator>Ge, Liqin</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><orcidid>https://orcid.org/0000-0001-9622-3732</orcidid><orcidid>https://orcid.org/0000-0002-9399-8249</orcidid></search><sort><creationdate>20230510</creationdate><title>Layer-by-Layer Microneedle-Mediated rhEGF Transdermal Delivery for Enhanced Wound Epidermal Regeneration and Angiogenesis</title><author>Yuan, Renqiang ; Yang, Ning ; Huang, Yueru ; Li, Weikun ; Zeng, Yi ; Liu, Zonghao ; Tan, Xin ; Feng, Fang ; Zhang, Qianli ; Su, Shao ; Chu, Cuilin ; Liu, Ling ; Ge, Liqin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a143t-c535e5e5d2fa4f1977c848e5f3c89f5ab502543a99da3b119d59b0a0640dcd393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animals</topic><topic>Biological and Medical Applications of Materials and Interfaces</topic><topic>Cell Proliferation</topic><topic>Endothelial Cells - metabolism</topic><topic>Epidermal Growth Factor - metabolism</topic><topic>Epidermis - metabolism</topic><topic>Humans</topic><topic>Rats</topic><topic>Recombinant Proteins</topic><topic>Wound Healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yuan, Renqiang</creatorcontrib><creatorcontrib>Yang, Ning</creatorcontrib><creatorcontrib>Huang, Yueru</creatorcontrib><creatorcontrib>Li, Weikun</creatorcontrib><creatorcontrib>Zeng, Yi</creatorcontrib><creatorcontrib>Liu, Zonghao</creatorcontrib><creatorcontrib>Tan, Xin</creatorcontrib><creatorcontrib>Feng, Fang</creatorcontrib><creatorcontrib>Zhang, Qianli</creatorcontrib><creatorcontrib>Su, Shao</creatorcontrib><creatorcontrib>Chu, Cuilin</creatorcontrib><creatorcontrib>Liu, Ling</creatorcontrib><creatorcontrib>Ge, Liqin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>ACS applied materials & interfaces</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yuan, Renqiang</au><au>Yang, Ning</au><au>Huang, Yueru</au><au>Li, Weikun</au><au>Zeng, Yi</au><au>Liu, Zonghao</au><au>Tan, Xin</au><au>Feng, Fang</au><au>Zhang, Qianli</au><au>Su, Shao</au><au>Chu, Cuilin</au><au>Liu, Ling</au><au>Ge, Liqin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Layer-by-Layer Microneedle-Mediated rhEGF Transdermal Delivery for Enhanced Wound Epidermal Regeneration and Angiogenesis</atitle><jtitle>ACS applied materials & interfaces</jtitle><addtitle>ACS Appl. Mater. Interfaces</addtitle><date>2023-05-10</date><risdate>2023</risdate><volume>15</volume><issue>18</issue><spage>21929</spage><epage>21940</epage><pages>21929-21940</pages><issn>1944-8244</issn><eissn>1944-8252</eissn><abstract>Appropriate treatments for acute traumas tend to avoid hemorrhages, vascular damage, and infections. However, in the homeostasis-imbalanced wound microenvironment, currently developed therapies could not precisely and controllably deliver biomacromolecular drugs, which are confronted with challenges due to large molecular weight, poor biomembrane permeability, low dosage, rapid degradation, and bioactivity loss. To conquer this, we construct a simple and effective layer-by-layer (LBL) self-assembly transdermal delivery patch, bearing microneedles (MN) coated with recombinant human epidermal growth factor (LBL MN-rhEGF) for a sustained release to wound bed driven by typical electrostatic force. Pyramidal LBL MN-rhEGF patches hold so enough mechanical strength to penetrate the stratum corneum, and generated microchannels allow rhEGF direct delivery in situ. The administrable delivery of biomacromolecular rhEGF through hierarchically coated MN arrays follows the diffusion mechanism of Fick’s second law. Numerous efforts further have illustrated that finger-pressing LBL MN-rhEGF patches could not only promote cell proliferation of normal human dermal fibroblasts (NHDF) and human umbilical vein endothelial cells (HUVEC) in vitro but also take significant effects (regenerative epidermis: ∼144 μm; pro-angiogenesis: higher CD31 expression) in accelerating wound healing of mechanically injured rats, compared to the traditional dressing, which relies on passive diffusion. 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subjects | Animals Biological and Medical Applications of Materials and Interfaces Cell Proliferation Endothelial Cells - metabolism Epidermal Growth Factor - metabolism Epidermis - metabolism Humans Rats Recombinant Proteins Wound Healing |
title | Layer-by-Layer Microneedle-Mediated rhEGF Transdermal Delivery for Enhanced Wound Epidermal Regeneration and Angiogenesis |
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