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A biodegradable stimulus-responsive hydrogel was synthesized in the present study to evaluate its application as an environmentally sensitive carrier for on-demand intraoral drug delivery. The hydrogel was synthesized from diacrylate-containing polyethylene glycol\u2013based scaffolds and a cysteine-terminated peptide crosslinker (CGPQG\u2193IWGQC) via a Michael-type addition reaction. Because CGPQG\u2193IWGQC can be cleaved by matrix metalloproteinase 8 (MMP-8), minocycline hydrochloride, bovine serum albumin, or an antibacterial peptide (KSL) was incorporated into the scaffolds to evaluate the MMP-8-responsive release behavior of the on-demand drug delivery system. Hydrogel characterization and gelation kinetics were examined with gel time, Fourier-transform infrared spectroscopy, scanning electron microscopy, and measurements of rheologic parameters. Degradation behavior and MMP-8-responsive drug release were performed by high-performance liquid chromatography and protein-specific assay. Biocompatibility evaluation indicated that the hydrogels were noncytotoxic. Antibacterial testing demonstrated that the released drugs were able to maintain bioactivity. Taken together, these results suggest that the MMP-8-sensitive hydrogel is a promising candidate for on-demand intraoral localized drug delivery. Because MMP-8 is one of the most important biomarkers for periodontitis, the MMP-8-responsive hydrogel has potential to be used for in situ adaptive degradation in response to chronic periodontitis and peri-implantitis. This notion has to be tested in animal models of periodontal disease.<\/jats:p>","DOI":"10.1177\/0022034519831931","type":"journal-article","created":{"date-parts":[[2019,3,15]],"date-time":"2019-03-15T23:38:39Z","timestamp":1552693119000},"page":"564-571","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":76,"title":["MMP-8-Responsive Polyethylene Glycol Hydrogel for Intraoral Drug Delivery"],"prefix":"10.1177","volume":"98","author":[{"given":"J.","family":"Guo","sequence":"first","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Sun","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Tang","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Hong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Yang","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.R.","family":"Tay","sequence":"additional","affiliation":[{"name":"Department of Endodontics, The Dental College of Georgia, Augusta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Huang","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,3,15]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986708785747490"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1088\/1748-6041\/4\/2\/022001"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/psc.2836"},{"issue":"12","key":"e_1_3_3_5_1","first-page":"4252","article-title":"Poly(ethylene glycol)-containing hydrogels promote the release of primary granules from human blood-derived polymorphonuclear leukocytes","volume":"102","author":"Cohen HC","year":"2014","unstructured":"Cohen HC, Lieberthal TJ, Kao WJ. 2014. 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