{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T18:04:50Z","timestamp":1781028290536,"version":"3.54.1"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Beijing University of Chinese Medicine Vertical Research and Development Fund","award":["2022-ZXFZJJ-018"],"award-info":[{"award-number":["2022-ZXFZJJ-018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Chronic refractory wounds are characterized by persistent inflammation and bacterial colonization. This study aims to develop a sequential-release hydrogel incorporating emodin (EMO) and shikonin (SKN) to provide coordinated antibacterial and anti-inflammatory effects tailored to the wound-healing process.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A dynamic hydrogel was fabricated via Schiff base crosslinking between chlorogenic acid-grafted chitosan and oxidized Bletilla striata polysaccharide. EMO alkaline solution and SKN-loaded nanostructured lipid carriers were incorporated. The release profiles were evaluated in vitro. Antibacterial activity was assessed using the inhibition zone assay, and anti-inflammatory activity was determined by LPS-induced NO release assay. Skin irritation was tested using an impaired skin model, and wound-healing efficacy was evaluated in a diabetic rat model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key findings<\/jats:title>\n                    <jats:p>SKN exhibited a consistently slower release rate than EMO, confirming the sequential release profile. The drug-loaded hydrogel demonstrated significant antibacterial and anti-inflammatory activities in vitro without causing skin irritation. In diabetic wound rats, the hydrogel markedly accelerated wound closure, reduced inflammatory infiltration, and promoted tissue regeneration compared with free drug treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The sequential-release hydrogel loaded with EMO and SKN represents a promising therapeutic strategy for chronic refractory wounds by providing spatially and temporally controlled antibacterial and anti-inflammatory effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jpp\/rgag050","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T11:48:02Z","timestamp":1778845682000},"source":"Crossref","is-referenced-by-count":0,"title":["Development and evaluation of a sequential-release hydrogel loaded emodin and shikonin for chronic refractory wound 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