Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/155231
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dc.contributor.authorNguyen, Dang Trien_US
dc.contributor.authorSoeranaya, Bob Hartadhi Tjien_US
dc.contributor.authorTruong, Thi Hong Anhen_US
dc.contributor.authorDang, Tram Thuyen_US
dc.date.accessioned2022-03-01T05:40:22Z-
dc.date.available2022-03-01T05:40:22Z-
dc.date.issued2020-
dc.identifier.citationNguyen, D. T., Soeranaya, B. H. T., Truong, T. H. A. & Dang, T. T. (2020). Modular design of a hybrid hydrogel for protease-triggered enhancement of drug delivery to regulate TNF-α production by pro-inflammatory macrophages. Acta Biomaterialia, 117, 167-179. https://dx.doi.org/10.1016/j.actbio.2020.09.026en_US
dc.identifier.issn1742-7061en_US
dc.identifier.urihttps://hdl.handle.net/10356/155231-
dc.description.abstractSystemic drug administration has conventionally been prescribed to alleviate persistent local inflammation which is prevalent in chronic diseases. However, this approach is associated with drug-induced toxicity, particularly when the dosage exceeds that necessitated by pathological conditions of diseased tissues. Herein, we developed a modular hybrid hydrogel which could be triggered to release an anti-inflammatory drug upon exposure to elevated protease activity associated with inflammatory diseases. Modular design of the hybrid hydrogel enabled independent optimization of its protease-cleavable and drug-loaded subdomains to facilitate hydrogel formation, cleavability by matrix-metalloprotease-9 (MMP-9), and tuning drug release rate. In vitro study demonstrated the protease-triggered enhancement of drug release from the hybrid hydrogel system for effective inhibition of TNF-α production by pro-inflammatory macrophages and suggested its potential to mitigate drug-induced cytotoxicity. Using non-invasive imaging to monitor the activity of reactive oxygen species in biomaterial-induced host response, we confirmed that the hybrid hydrogel and its constituent materials did not induce adverse immune response after 5 days following their subcutaneous injection in immuno-competent mice. We subsequently incorporated this hybrid hydrogel onto a commercial wound dressing which could release the drug upon exposure to MMP-9. Together, our findings suggested that this hybrid hydrogel might be a versatile platform for on-demand drug delivery via either injectable or topical application to modulate inflammation in chronic diseases.en_US
dc.description.sponsorshipAgency for Science, Technology and Research (A*STAR)en_US
dc.description.sponsorshipMinistry of Education (MOE)en_US
dc.description.sponsorshipNanyang Technological Universityen_US
dc.language.isoenen_US
dc.relationARISE/2017/16en_US
dc.relationM4082061.120en_US
dc.relationM4081759.120en_US
dc.relationM4011637.120en_US
dc.relationH19/01/a0/HH9en_US
dc.relation.ispartofActa Biomaterialiaen_US
dc.rights© 2020 Acta Materialia Inc. All rights reserved. This paper was published by Elsevier Ltd in Acta Biomaterialia and is made available with permission of Acta Materialia Inc.en_US
dc.subjectEngineering::Bioengineeringen_US
dc.titleModular design of a hybrid hydrogel for protease-triggered enhancement of drug delivery to regulate TNF-α production by pro-inflammatory macrophagesen_US
dc.typeJournal Articleen
dc.contributor.schoolSchool of Chemical and Biomedical Engineeringen_US
dc.identifier.doi10.1016/j.actbio.2020.09.026-
dc.description.versionSubmitted/Accepted versionen_US
dc.identifier.pmid32977069-
dc.identifier.scopus2-s2.0-85092257463-
dc.identifier.volume117en_US
dc.identifier.spage167en_US
dc.identifier.epage179en_US
dc.subject.keywordsMatrix-Metalloprotease-9en_US
dc.subject.keywordsHydrogelen_US
dc.description.acknowledgementThis work was supported by the Ageing Research Institute for Society and Education (ARISE), Nanyang Technological University (NTU), Singapore (ARISE/2017/16, M4082061.120), the NTU Startup Grant (M4081759.120), and the Singapore Ministry of Education Academic Tier 1 Grant (M4011637.120). This research is also supported by the Agency for Science, Technology and Research (A∗STAR) under its Industry Alignment Fund – Pre-Positioning Programme (IAF-PP) grant number H19/01/a0/HH9, Wound Care Innovations for the Tropics (WCIT) Programme. Dang T. Nguyen was supported by the NTU Research Scholarship for graduate study.en_US
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