{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:33:16Z","timestamp":1789140796568,"version":"build-2803163510"},"reference-count":22,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012131","name":"Liaoning Province Science and Technology Joint Program","doi-asserted-by":"publisher","award":["2025-MSLH-491"],"award-info":[{"award-number":["2025-MSLH-491"]}],"id":[{"id":"10.13039\/501100012131","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Basic Scientific Research Projects in Colleges and Universities of Liaoning Provincial Department of Education","award":["LJ222410162070"],"award-info":[{"award-number":["LJ222410162070"]}]},{"name":"Basic Scientific Research Projects in Colleges and Universities of Liaoning Provincial Department of Education","award":["LJ212510162012"],"award-info":[{"award-number":["LJ212510162012"]}]},{"name":"Shenyang Public Health R&D Science and Technology Project","award":["24-214-3-16"],"award-info":[{"award-number":["24-214-3-16"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gels"],"abstract":"<jats:p>Infectious wounds are plagued by persistent infection, uncontrolled inflammation, and delayed repair, while traditional therapies suffer from the poor solubility of natural drugs, low bioavailability, and bacterial drug resistance. To address these issues, this study developed a photo-responsive chitosan composite hydrogel (BBR-AS@Ce6@Matrix) cross-linked by chitosan (CS) and oxidized sodium alginate (OSA), co-loaded with Berberine\u2013Asiaticoside cocrystal (BBR-AS) and chlorin e6-loaded chitosan nanoparticles (Ce6@CS NPs). The BBR-AS co-crystal was prepared by solvent method and verified to significantly improve the solubility and dissolution of asiaticoside. The Ce6@CS NPs were fabricated via non-solvent-assisted counterion complexation, showing high encapsulation efficiency, uniform particle size, and efficient singlet oxygen generation under irradiation. The hydrogel exhibited a three-dimensional porous network, favorable rheology, high water content, pH-dependent swelling and erosion behaviors, and significantly promoted BBR\/AS release in vitro. In vitro experiments demonstrated strong antibacterial activity against Escherichia coli and Staphylococcus aureus, good cytocompatibility, and enhanced migration of L929 and Hacat cells. In a rat infectious wound model, the hydrogel combined with light irradiation markedly accelerated wound closure, promoted collagen deposition and angiogenesis, upregulated VEGF\/CD31, and downregulated TNF-\u03b1\/IL-6. In conclusion, BBR-AS@Ce6@Matrix integrates co-crystal solubilization, nanoparticle-facilitated release, and photodynamic synergy to achieve antibacterial, anti-inflammatory, pro-angiogenic and tissue remodeling effects, providing a promising multifunctional platform for infectious wound repair.<\/jats:p>","DOI":"10.3390\/gels12070620","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T14:17:51Z","timestamp":1783606671000},"page":"620","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Study on the Preparation of a Photo-Responsive Hydrogel Loaded with Berberine\u2013Asiaticoside Cocrystal and Its Therapeutic Effect on Infected Wounds"],"prefix":"10.3390","volume":"12","author":[{"given":"Muxi","family":"Sui","sequence":"first","affiliation":[{"name":"First Clinical College, Liaoning University of Traditional Chinese Medicine, Shenyang 110033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9444-1855","authenticated-orcid":false,"given":"Jin","family":"Niu","sequence":"additional","affiliation":[{"name":"School of Medical Humanities, China Medical University, Shenyang 110122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuwen","family":"Pang","sequence":"additional","affiliation":[{"name":"First Clinical College, Liaoning University of Traditional Chinese Medicine, Shenyang 110033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Zhao","sequence":"additional","affiliation":[{"name":"First Clinical College, Liaoning University of Traditional Chinese Medicine, Shenyang 110033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingxi","family":"Zhou","sequence":"additional","affiliation":[{"name":"First Clinical College, Liaoning University of Traditional Chinese Medicine, Shenyang 110033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengdi","family":"Zhao","sequence":"additional","affiliation":[{"name":"First Clinical College, Liaoning University of Traditional Chinese Medicine, Shenyang 110033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1280-2468","authenticated-orcid":false,"given":"Yongai","family":"Xiong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"First Clinical College, Liaoning University of Traditional Chinese Medicine, Shenyang 110033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Schilrreff, P., and Alexiev, U. (2022). Chronic Inflammation in Non-Healing Skin Wounds and Promising Natural Bioactive Compounds Treatment. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094928"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"eadt0882","DOI":"10.1126\/scitranslmed.adt0882","article-title":"A microfluidic wearable device for wound exudate management and analysis in human chronic wounds","volume":"17","author":"Wang","year":"2025","journal-title":"Sci. Transl. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5370","DOI":"10.2174\/0109298673312649240829103906","article-title":"Trends in the Treatment of Chronic Wounds","volume":"32","author":"Sharma","year":"2025","journal-title":"Curr. Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.12968\/bjcn.2021.26.Sup6.S22","article-title":"Wound infections: An overview","volume":"26","author":"Williams","year":"2021","journal-title":"Br. J. Community Nurs."},{"key":"ref_5","first-page":"183","article-title":"Treatment of chronic wounds","volume":"148","author":"Binder","year":"2023","journal-title":"Dtsch. Med. Wochenschr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e2200014","DOI":"10.1002\/mabi.202200014","article-title":"An Overview on the Recent Advances in the Treatment of Infected Wounds: Antibacterial Wound Dressings","volume":"22","author":"Mirhaj","year":"2022","journal-title":"Macromol. Biosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"155258","DOI":"10.1016\/j.phymed.2023.155258","article-title":"Inhibition of inflammation by berberine: Molecular mechanism and network pharmacology analysis","volume":"128","author":"Wang","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zhu, C., Li, K., Peng, X.X., Yao, T.J., Wang, Z.Y., Hu, P., Cai, D., and Liu, H.Y. (2022). Berberine a traditional Chinese drug repurposing: Its actions in inflammation-associated ulcerative colitis and cancer therapy. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1083788"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1080\/15384101.2022.2100682","article-title":"Protective effect of berberine against LPS-induced injury in the intestine: A review","volume":"21","author":"Izadparast","year":"2022","journal-title":"Cell Cycle"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Razif, R., Fadilah, N.I.M., Ahmad, H., Hao, D.L.Q., Maarof, M., and Fauzi, M.B. (2025). Asiaticoside-Loaded Multifunctional Bioscaffolds for Enhanced Hyperglycemic Wound Healing. Biomedicines, 13.","DOI":"10.3390\/biomedicines13020277"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"tkaf009","DOI":"10.1093\/burnst\/tkaf009","article-title":"Asiaticoside-nitric oxide synergistically accelerate diabetic wound healing by regulating key metabolites and SRC\/STAT3 signaling","volume":"13","author":"Mu","year":"2025","journal-title":"Burn. Trauma"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1080\/13880209.2026.2638602","article-title":"Therapeutic potential of Asiaticoside in wound healing after endoscopic submucosal dissection (ESD)","volume":"64","author":"Li","year":"2026","journal-title":"Pharm. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"102831","DOI":"10.1016\/j.pdpdt.2022.102831","article-title":"Photodynamic therapy for treatment of infected burns","volume":"38","author":"Mencalha","year":"2022","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"102285","DOI":"10.1016\/j.pdpdt.2021.102285","article-title":"Photodynamic therapy for treatment of Staphylococcus aureus infections","volume":"34","author":"Palavecino","year":"2021","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1021\/acsbiomaterials.2c01297","article-title":"Chitosan Derivatives as Carriers for Drug Delivery and Biomedical Applications","volume":"9","author":"Manna","year":"2023","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2300945","DOI":"10.1080\/10717544.2023.2300945","article-title":"Advancing burn wound treatment: Exploring hydrogel as a transdermal drug delivery system","volume":"31","author":"Goh","year":"2024","journal-title":"Drug Deliv."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"114346","DOI":"10.1016\/j.colsurfb.2024.114346","article-title":"Multifunctional injectable oxidized sodium alginate\/carboxymethyl chitosan hydrogel for rapid hemostasis","volume":"245","author":"Liu","year":"2025","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"101669","DOI":"10.1016\/j.mtbio.2025.101669","article-title":"Co-encapsulated Ce6 + CpG and biopeptide-modified liposomes for enhanced transdermal photo-immunotherapy of superficial tumors","volume":"32","author":"Wang","year":"2025","journal-title":"Mater. Today Bio"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"128086","DOI":"10.1016\/j.ijbiomac.2023.128086","article-title":"Pickering emulsions stabilized by chitosan-flaxseed gum-hyaluronic acid nanoparticles for controlled topical release of ferulic acid","volume":"255","author":"Li","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1007\/s13346-021-00932-7","article-title":"Therapy of infected wounds: Overcoming clinical challenges by advanced drug delivery systems","volume":"11","author":"Kaiser","year":"2021","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_21","unstructured":"(2009). Biological Evaluation of Medical Devices Part 5: Tests for In Vitro Cytotoxicity (Standard No. ISO 10993-5:2009). Available online: https:\/\/www.iso.org\/standard\/36406.html."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1039\/D2NR04908B","article-title":"An antioxidant and antibacterial polydopamine-modified thermo-sensitive hydrogel dressing for Staphylococcus aureus-infected wound healing","volume":"15","author":"Ge","year":"2023","journal-title":"Nanoscale"}],"container-title":["Gels"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2310-2861\/12\/7\/620\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T12:17:02Z","timestamp":1783685822000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2310-2861\/12\/7\/620"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,9]]},"references-count":22,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["gels12070620"],"URL":"https:\/\/doi.org\/10.3390\/gels12070620","relation":{},"ISSN":["2310-2861"],"issn-type":[{"value":"2310-2861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,9]]}}}