Hydrolytically Degradable Microgels with Tunable Mechanical Properties Modulate the Host Immune Response
Hydrogel microparticles (microgels) are an attractive approach for therapeutic delivery because of their modularity, injectability, and enhanced integration with the host tissue. Multiple microgel fabrication strategies and chemistries have been implemented, yet manipulation of microgel degradabilit...
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description | Hydrogel microparticles (microgels) are an attractive approach for therapeutic delivery because of their modularity, injectability, and enhanced integration with the host tissue. Multiple microgel fabrication strategies and chemistries have been implemented, yet manipulation of microgel degradability and its effect on in vivo tissue responses remains underexplored. Here, the authors report a facile method to synthesize microgels crosslinked with ester‐containing junctions to afford tunable degradation kinetics. Monodisperse microgels of maleimide‐functionalized poly(ethylene‐glycol) are generated using droplet microfluidics crosslinked with thiol‐terminated, ester‐containing molecules. Tunable mechanics are achievable based on the ratio of degradable to nondegradable crosslinkers in the continuous phase. Degradation in an aqueous medium leads to microgel deformation based on swelling and a decrease in elastic modulus. Furthermore, degradation byproducts are cytocompatible and do not cause monocytic cell activation under noninflammatory conditions. These injectable microgels possess time‐dependent degradation on the order of weeks in vivo. Lastly, the evaluation of tissue responses in a subcutaneous dorsal pocket shows a dynamic type‐1 like immune response to the synthetic microgels, driven by interferon gamma (IFN‐γ ) expression, which can be moderated by tuning the degradation properties. Collectively, this study demonstrates the development of a hydrolytic microgel platform that can be adapted to desired host tissue immune responses.
Hydrolytically susceptible ethylene linkers are used for microparticle crosslinking to fabricate degradable droplet microfluidic based microgels for therapeutic delivery. The tunability and degradability conferred by the ester‐based degradation in vivo regulate the infiltration of immune cells to the implant site and the host immune polarization. |
doi_str_mv | 10.1002/smll.202106896 |
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Hydrolytically susceptible ethylene linkers are used for microparticle crosslinking to fabricate degradable droplet microfluidic based microgels for therapeutic delivery. The tunability and degradability conferred by the ester‐based degradation in vivo regulate the infiltration of immune cells to the implant site and the host immune polarization.</description><identifier>ISSN: 1613-6810</identifier><identifier>EISSN: 1613-6829</identifier><identifier>DOI: 10.1002/smll.202106896</identifier><identifier>PMID: 35274457</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Aqueous solutions ; Crosslinking ; Degradation ; Elastic deformation ; Esters ; Hydrogels ; Immune system ; Immunity ; In vivo methods and tests ; Injectability ; Interferon ; Mechanical properties ; Microfluidics ; Microgels ; Microparticles ; Modularity ; Modulus of elasticity ; Nanotechnology ; PEG‐4MAL ; Polyethylene Glycols</subject><ispartof>Small (Weinheim an der Bergstrasse, Germany), 2022-09, Vol.18 (36), p.e2106896-n/a</ispartof><rights>2022 Wiley‐VCH GmbH</rights><rights>2022 Wiley-VCH GmbH.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4696-e404de75268936d9a8ee6492d6e5903edf37b3abc6f2222362cdf3ab1d3dd8a83</citedby><cites>FETCH-LOGICAL-c4696-e404de75268936d9a8ee6492d6e5903edf37b3abc6f2222362cdf3ab1d3dd8a83</cites><orcidid>0000-0001-9661-7221 ; 0000-0001-6602-2518</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fsmll.202106896$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fsmll.202106896$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35274457$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Coronel, María M.</creatorcontrib><creatorcontrib>Martin, Karen E.</creatorcontrib><creatorcontrib>Hunckler, Michael D.</creatorcontrib><creatorcontrib>Kalelkar, Pranav</creatorcontrib><creatorcontrib>Shah, Rahul M.</creatorcontrib><creatorcontrib>García, Andrés J.</creatorcontrib><title>Hydrolytically Degradable Microgels with Tunable Mechanical Properties Modulate the Host Immune Response</title><title>Small (Weinheim an der Bergstrasse, Germany)</title><addtitle>Small</addtitle><description>Hydrogel microparticles (microgels) are an attractive approach for therapeutic delivery because of their modularity, injectability, and enhanced integration with the host tissue. Multiple microgel fabrication strategies and chemistries have been implemented, yet manipulation of microgel degradability and its effect on in vivo tissue responses remains underexplored. Here, the authors report a facile method to synthesize microgels crosslinked with ester‐containing junctions to afford tunable degradation kinetics. Monodisperse microgels of maleimide‐functionalized poly(ethylene‐glycol) are generated using droplet microfluidics crosslinked with thiol‐terminated, ester‐containing molecules. Tunable mechanics are achievable based on the ratio of degradable to nondegradable crosslinkers in the continuous phase. Degradation in an aqueous medium leads to microgel deformation based on swelling and a decrease in elastic modulus. Furthermore, degradation byproducts are cytocompatible and do not cause monocytic cell activation under noninflammatory conditions. These injectable microgels possess time‐dependent degradation on the order of weeks in vivo. Lastly, the evaluation of tissue responses in a subcutaneous dorsal pocket shows a dynamic type‐1 like immune response to the synthetic microgels, driven by interferon gamma (IFN‐γ ) expression, which can be moderated by tuning the degradation properties. Collectively, this study demonstrates the development of a hydrolytic microgel platform that can be adapted to desired host tissue immune responses.
Hydrolytically susceptible ethylene linkers are used for microparticle crosslinking to fabricate degradable droplet microfluidic based microgels for therapeutic delivery. The tunability and degradability conferred by the ester‐based degradation in vivo regulate the infiltration of immune cells to the implant site and the host immune polarization.</description><subject>Aqueous solutions</subject><subject>Crosslinking</subject><subject>Degradation</subject><subject>Elastic deformation</subject><subject>Esters</subject><subject>Hydrogels</subject><subject>Immune system</subject><subject>Immunity</subject><subject>In vivo methods and tests</subject><subject>Injectability</subject><subject>Interferon</subject><subject>Mechanical properties</subject><subject>Microfluidics</subject><subject>Microgels</subject><subject>Microparticles</subject><subject>Modularity</subject><subject>Modulus of elasticity</subject><subject>Nanotechnology</subject><subject>PEG‐4MAL</subject><subject>Polyethylene Glycols</subject><issn>1613-6810</issn><issn>1613-6829</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9P2zAUx60JNBjbdcfJEhcuLf6ROM4JTQVWpFZMGztbTvzaGDlxZyeg_Pe4KuuAC77Yev74o_f8RegrJVNKCDuPrXNTRhglQpbiAzqmgvKJkKw82J8pOUKfYrwnhFOWFR_REc9ZkWV5cYya-WiCd2Nva-3ciC9hHbTRlQO8tHXwa3ARP9q-wXdDtytD3ehui-OfwW8g9BYiXnozON0D7hvAcx97fNO2Qwf4F8SN7yJ8Rocr7SJ8ed5P0J_rq7vZfLK4_XEz-76Y1JkoxQQykhkocpbG4cKUWgKIrGRGQF4SDmbFi4rrqhYrlhYXrE4lXVHDjZFa8hN0sfNuhqoFU0PXB-3UJthWh1F5bdXrm842au0fFCVMSi5FMpw9G4L_O0DsVWtjDc7pDvwQFRNcFjQveZHQ0zfovR9Cl-ZTrKCU5iynW-F0R6X_jDHAat8NJWqbotqmqPYppgffXs6wx__FloByBzxaB-M7OvV7uVj8lz8BO0yr4w</recordid><startdate>20220901</startdate><enddate>20220901</enddate><creator>Coronel, María M.</creator><creator>Martin, Karen E.</creator><creator>Hunckler, Michael D.</creator><creator>Kalelkar, Pranav</creator><creator>Shah, Rahul M.</creator><creator>García, Andrés J.</creator><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>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>L7M</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9661-7221</orcidid><orcidid>https://orcid.org/0000-0001-6602-2518</orcidid></search><sort><creationdate>20220901</creationdate><title>Hydrolytically Degradable Microgels with Tunable Mechanical Properties Modulate the Host Immune Response</title><author>Coronel, María M. ; Martin, Karen E. ; Hunckler, Michael D. ; Kalelkar, Pranav ; Shah, Rahul M. ; García, Andrés J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4696-e404de75268936d9a8ee6492d6e5903edf37b3abc6f2222362cdf3ab1d3dd8a83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Aqueous solutions</topic><topic>Crosslinking</topic><topic>Degradation</topic><topic>Elastic deformation</topic><topic>Esters</topic><topic>Hydrogels</topic><topic>Immune system</topic><topic>Immunity</topic><topic>In vivo methods and tests</topic><topic>Injectability</topic><topic>Interferon</topic><topic>Mechanical properties</topic><topic>Microfluidics</topic><topic>Microgels</topic><topic>Microparticles</topic><topic>Modularity</topic><topic>Modulus of elasticity</topic><topic>Nanotechnology</topic><topic>PEG‐4MAL</topic><topic>Polyethylene Glycols</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Coronel, María M.</creatorcontrib><creatorcontrib>Martin, Karen E.</creatorcontrib><creatorcontrib>Hunckler, Michael D.</creatorcontrib><creatorcontrib>Kalelkar, Pranav</creatorcontrib><creatorcontrib>Shah, Rahul M.</creatorcontrib><creatorcontrib>García, Andrés J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Small (Weinheim an der Bergstrasse, Germany)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Coronel, María M.</au><au>Martin, Karen E.</au><au>Hunckler, Michael D.</au><au>Kalelkar, Pranav</au><au>Shah, Rahul M.</au><au>García, Andrés J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hydrolytically Degradable Microgels with Tunable Mechanical Properties Modulate the Host Immune Response</atitle><jtitle>Small (Weinheim an der Bergstrasse, Germany)</jtitle><addtitle>Small</addtitle><date>2022-09-01</date><risdate>2022</risdate><volume>18</volume><issue>36</issue><spage>e2106896</spage><epage>n/a</epage><pages>e2106896-n/a</pages><issn>1613-6810</issn><eissn>1613-6829</eissn><abstract>Hydrogel microparticles (microgels) are an attractive approach for therapeutic delivery because of their modularity, injectability, and enhanced integration with the host tissue. Multiple microgel fabrication strategies and chemistries have been implemented, yet manipulation of microgel degradability and its effect on in vivo tissue responses remains underexplored. Here, the authors report a facile method to synthesize microgels crosslinked with ester‐containing junctions to afford tunable degradation kinetics. Monodisperse microgels of maleimide‐functionalized poly(ethylene‐glycol) are generated using droplet microfluidics crosslinked with thiol‐terminated, ester‐containing molecules. Tunable mechanics are achievable based on the ratio of degradable to nondegradable crosslinkers in the continuous phase. Degradation in an aqueous medium leads to microgel deformation based on swelling and a decrease in elastic modulus. Furthermore, degradation byproducts are cytocompatible and do not cause monocytic cell activation under noninflammatory conditions. These injectable microgels possess time‐dependent degradation on the order of weeks in vivo. Lastly, the evaluation of tissue responses in a subcutaneous dorsal pocket shows a dynamic type‐1 like immune response to the synthetic microgels, driven by interferon gamma (IFN‐γ ) expression, which can be moderated by tuning the degradation properties. Collectively, this study demonstrates the development of a hydrolytic microgel platform that can be adapted to desired host tissue immune responses.
Hydrolytically susceptible ethylene linkers are used for microparticle crosslinking to fabricate degradable droplet microfluidic based microgels for therapeutic delivery. The tunability and degradability conferred by the ester‐based degradation in vivo regulate the infiltration of immune cells to the implant site and the host immune polarization.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>35274457</pmid><doi>10.1002/smll.202106896</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-9661-7221</orcidid><orcidid>https://orcid.org/0000-0001-6602-2518</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Aqueous solutions Crosslinking Degradation Elastic deformation Esters Hydrogels Immune system Immunity In vivo methods and tests Injectability Interferon Mechanical properties Microfluidics Microgels Microparticles Modularity Modulus of elasticity Nanotechnology PEG‐4MAL Polyethylene Glycols |
title | Hydrolytically Degradable Microgels with Tunable Mechanical Properties Modulate the Host Immune Response |
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