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Formulation with acceptable physical properties and C-PC release was studied for oxidative stress markers, antioxidant biomarkers, and wound healing effect in animal models. WPINF had acceptable particle size (26.59\u2013153.5\u00a0nm), % EE (65.76\u201395.98%), and zeta potential (22.3\u201326.1 mV). The developed hydrogels exhibited neutral pH values (6.97\u20137.10), optimal spreadability (5.60\u20137.50\u00a0cm), and viscosity (123\u2013209\u00a0Pa). HEC-based hydrogel (F1) showed superior C-PC release which was found to follow Higuchi diffusion. In vivo, hydrogel formulations (with and without probiotic) showed significantly reduced oxidative stress markers, with MDA reduced by 54.76\u201398.58% and antioxidant biomarkers (GSH and TAC) ensuring successful delivery of therapeutic compounds. Histological analysis showed improved re-epithelialization, reduced inflammation, and well-formed granulation tissue in treated groups, with probiotic-C-PC group demonstrating additional immunomodulatory effects. The study highlights promising potential of C-PC-probiotic hydrogels as a safe\u00a0and effective biotherapeutics for wound healing, supporting their advancement into further clinical investigations to validate their efficacy in humans.\n                  <\/jats:p>","DOI":"10.1007\/s12602-025-10635-x","type":"journal-article","created":{"date-parts":[[2025,7,12]],"date-time":"2025-07-12T08:15:43Z","timestamp":1752308143000},"page":"2037-2055","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Innovative Hydrogel Formulation Combining Phycocyanin and Probiotic for Enhancing Skin Regeneration and Accelerated Wound Healing: A Preclinical Investigation in Wistar Rats"],"prefix":"10.1007","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8177-925X","authenticated-orcid":false,"given":"Asmaa","family":"Negm El-Dein","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1138-9133","authenticated-orcid":false,"given":"Tarek N.","family":"Soliman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1493-0386","authenticated-orcid":false,"given":"Asmaa","family":"Ezzat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5275-0810","authenticated-orcid":false,"given":"Marwa Adel","family":"Abd El-Fattah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3642-1571","authenticated-orcid":false,"given":"Hanan Farouk","family":"Aly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7753-628X","authenticated-orcid":false,"given":"Eman A.","family":"Younis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7495-3950","authenticated-orcid":false,"given":"Nasser S.","family":"Flefil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,12]]},"reference":[{"issue":"17","key":"10635_CR1","doi-asserted-by":"publisher","first-page":"9573","DOI":"10.3390\/ijms23179573","volume":"23","author":"XT Trinh","year":"2022","unstructured":"Trinh XT, Long NV, Van Anh LT et al (2022) A comprehensive review of natural compounds for wound healing: targeting bioactivity perspective. 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