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Sulforaphane (SFN), a phytochemical present in crucifers, has been shown to have anti-inflammatory and immunoregulatory properties, yet its influences on immune cell activation as well as in graft survival are still unknown. Thus, the aim was to evaluate SFN\u2019s effect, and to improve efficacy, efficiency, and availability, it was incorporated into thermosensitive polymeric hydrogels, to prevent AR in skin transplant (Tx) model mice. A thermosensitive hydrogel containing SFN (0.1%) and hyaluronic acid (HA) (0.5%) dispersed in a poloxamer matrix (PL407 at 20% w\/v) was developed (GS-PL407 20%, HA and SFN) and characterized as a liquid-viscous hydrogel. The fully MHC-incompatible skin Tx procedure was performed by using donor skin Balb\/c mice, transplanted into C57BL\/6 recipient mice. The cytotoxicity test of GS was performed using in vitro assays with bone marrow-derived dendritic cells (BMDC). Treatment of BMDC with GS for 24 h presents no cytotoxicity. Untreated allograft mice present 100% of graft loss at day 9 post Tx. Remarkably, subcutaneous GS injection every 3 days promoted 80% of allograft survival for more than 14 days when compared with untreated recipients (p &amp;lt; 0.001). Histological analysis showed a lower level of inflammatory cells in the skin Tx of GS-treated mice. Flow cytometry analysis of draining lymph nodes at day 5 post Tx revealed that GS treatment reduced the frequency of DC and subtypes and function of the CD4+ T cells. In vitro GS-treated lipopolysaccharide-activated BMDC present less activation of costimulatory markers. Taken together, GS treatment reduced immune cell activation, postponing AR onset and prolonging allograft survival in Tx animals. This strategy highlights the role of SFN as a promising candidate for further studies in organ transplantation experiments and being tested combined with current immunosuppression protocols.<\/jats:p>","DOI":"10.1021\/acsabm.5c01022","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T13:09:59Z","timestamp":1761743399000},"page":"9780-9793","source":"Crossref","is-referenced-by-count":0,"title":["Sulforaphane-Loaded\nHydrogel Prolongs Fully MHC-Mismatched\nSkin Allograft Survival"],"prefix":"10.1021","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3780-1042","authenticated-orcid":true,"given":"Lorena","family":"Doretto-Silva","sequence":"first","affiliation":[{"name":"Federal University of ABC , , Santo Andre\u0301 , ,","place":["Sa\u0303o Paulo, Brazil, 09280-560"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Quadros-Pereira","sequence":"additional","affiliation":[{"name":"Federal University of ABC , , Santo Andre\u0301 , ,","place":["Sa\u0303o Paulo, Brazil, 09280-560"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anderson F.","family":"Sepulveda","sequence":"additional","affiliation":[{"name":"Federal University of ABC , , Santo Andre\u0301 , ,","place":["Sa\u0303o Paulo, Brazil, 09280-560"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor Y.","family":"Yariwake","sequence":"additional","affiliation":[{"name":"Federal University of ABC , , Santo Andre\u0301 , ,","place":["Sa\u0303o Paulo, Brazil, 09280-560"]},{"name":"University of Sa\u0303o Paulo , , ,","place":["Sa\u0303o Paulo, Brazil, 05508-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose\u0301 A. O.","family":"Nery-Neto","sequence":"additional","affiliation":[{"name":"Federal University of ABC , , Santo Andre\u0301 , ,","place":["Sa\u0303o Paulo, Brazil, 09280-560"]},{"name":"University of Sa\u0303o Paulo , , ,","place":["Sa\u0303o Paulo, Brazil, 05508-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eloisa M.","family":"da Silva","sequence":"additional","affiliation":[{"name":"Federal University of ABC , , Santo Andre\u0301 , ,","place":["Sa\u0303o Paulo, Brazil, 09280-560"]},{"name":"Federal University of Sa\u0303o Paulo , , ,","place":["Sa\u0303o Paulo, Brazil, 04021-001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabela L.","family":"Doretto","sequence":"additional","affiliation":[{"name":"University of Brasi\u0301lia , , ,","place":["Brasi\u0301lia, Brazil, 70910-900"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels O. S.","family":"Ca\u0302mara","sequence":"additional","affiliation":[{"name":"University of Sa\u0303o Paulo , , ,","place":["Sa\u0303o Paulo, Brazil, 05508-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele R.","family":"de Araujo","sequence":"additional","affiliation":[{"name":"Federal University of ABC , , Santo Andre\u0301 , ,","place":["Sa\u0303o Paulo, Brazil, 09280-560"]},{"name":"Federal University of Sa\u0303o Paulo , , ,","place":["Sa\u0303o Paulo, Brazil, 04021-001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinicius","family":"Andrade-Oliveira","sequence":"additional","affiliation":[{"name":"Federal University of ABC , , Santo Andre\u0301 , ,","place":["Sa\u0303o Paulo, Brazil, 09280-560"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"2026072914071133000_cit1","doi-asserted-by":"publisher","first-page":"6572338","DOI":"10.1155\/2022\/6572338","article-title":"The Most Promising\nBiomarkers of Allogeneic Kidney Transplant Rejection","volume":"2022","author":"Rogulska","year":"2022","journal-title":"J. Immunol. Res."},{"issue":"6","key":"2026072914071133000_cit2","doi-asserted-by":"publisher","DOI":"10.1111\/tid.13106","article-title":"Incidence and Risk Factors Associated\nwith Cytomegalovirus Infection after the Treatment of Acute Rejection\nduring the First Year in Kidney Transplant Recipients Receiving Preemptive\nTherapy","volume":"21","author":"Felipe","year":"2019","journal-title":"Transpl. Infect. Dis."},{"key":"2026072914071133000_cit3","doi-asserted-by":"publisher","first-page":"1357468","DOI":"10.3389\/fphar.2024.1357468","article-title":"Global Research Hotspots\nand Trends of Acute Rejection after Liver Transplantation from 1988\nto 2022: A Bibliometric Analysis","volume":"15","author":"Xiong","year":"2024","journal-title":"Front. Pharmacol"},{"issue":"4","key":"2026072914071133000_cit4","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1097\/MCP.0000000000001078","article-title":"Acute Rejection Post\nLung Transplant","volume":"30","author":"Hanks","year":"2024","journal-title":"Curr. Opin. Pulm. Med."},{"issue":"10","key":"2026072914071133000_cit5","doi-asserted-by":"publisher","first-page":"1828","DOI":"10.1016\/j.ajt.2024.04.006","article-title":"Incomplete Reporting\nof Clinically Significant Acute Rejection Episodes\nin the National Kidney Transplant Registry","volume":"24","author":"Yu","year":"2024","journal-title":"Am. J. Transplant."},{"key":"2026072914071133000_cit6","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.70028","article-title":"Production and Functional Verification of 8-Gene (GGTA1,\nCMAH, \u03924GalNT2, HCD46, HCD55, HCD59, HTBM, HCD39)-Edited Donor\nPigs for Xenotransplantation","volume":"58","author":"Wang","year":"2025","journal-title":"Cell Prolif"},{"key":"2026072914071133000_cit7","doi-asserted-by":"publisher","first-page":"30671","DOI":"10.34172\/bi.30671","article-title":"Overview of Dendritic Cells Subsets and Their Involvement\nin Immune-Related Pathological Disease","volume":"15","author":"Abbaszadeh","year":"2025","journal-title":"BioImpacts"},{"issue":"1","key":"2026072914071133000_cit8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5500\/wjt.v7.i1.1","article-title":"Old Game, New\nPlayers: Linking Classical Theories to New Trends in Transplant Immunology","volume":"7","author":"Silva","year":"2017","journal-title":"World J. Transplant."},{"issue":"5","key":"2026072914071133000_cit9","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1590\/S0482-50042010000500008","article-title":"Sistema\nImunita\u0301rio - Parte II: Fundamentos Da Resposta Imunolo\u0301gica\nMediada Por Linfo\u0301citos T e B","volume":"50","author":"Mesquita Ju\u0301nior","year":"2010","journal-title":"Rev. Bras.\nReumatol."},{"issue":"10","key":"2026072914071133000_cit10","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1038\/nri1702","article-title":"Antibody-Mediated\nOrgan-Allograft Rejection","volume":"5","author":"Colvin","year":"2005","journal-title":"Nat. Rev. Immunol."},{"issue":"2","key":"2026072914071133000_cit11","doi-asserted-by":"publisher","first-page":"S324","DOI":"10.1016\/j.jaci.2009.11.014","article-title":"Transplantation\nImmunology: Solid Organ and Bone Marrow","volume":"125","author":"Chinen","year":"2010","journal-title":"J.\nAllergy Clin. Immunol."},{"issue":"1","key":"2026072914071133000_cit12","doi-asserted-by":"publisher","first-page":"21207","DOI":"10.1038\/s41598-022-25445-2","article-title":"Calcineurin\nInhibitors\u2019 Impact on Cardiovascular and Renal Function, a\nDescriptive Study in Lung Transplant Recipients from the North of\nSpain","volume":"12","author":"Nogueiras-A\u0301lvarez","year":"2022","journal-title":"Sci. Rep."},{"issue":"15","key":"2026072914071133000_cit13","doi-asserted-by":"publisher","first-page":"4927","DOI":"10.3390\/jcm12154927","article-title":"Current\nTherapies in Kidney Transplant\nRejection","volume":"12","author":"Alasfar","year":"2023","journal-title":"J. Clin. Med."},{"issue":"1","key":"2026072914071133000_cit14","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1038\/s41398-020-0838-2","article-title":"Rapamycin Increases the Incidence\nof Neuropsychiatric Illness in Kidney Transplant Patients through\nthe Suppression of Neural Stem Cells","volume":"10","author":"Kim","year":"2020","journal-title":"Transl.\nPsychiatry"},{"issue":"1","key":"2026072914071133000_cit15","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1002\/lt.24873","article-title":"Environmental Peer\nPressure: CD4+ T Cell Help in Tolerance\nand Transplantation","volume":"24","author":"Tedesco","year":"2018","journal-title":"Liver Transpl"},{"issue":"1","key":"2026072914071133000_cit16","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1159\/000487501","article-title":"The Association Between\nOxidative Stress Alleviation\nvia Sulforaphane-Induced Nrf2-HO-1\/NQO-1 Signaling Pathway Activation\nand Chronic Renal Allograft Dysfunction Improvement. Kidney Blood\nPress","volume":"43","author":"Lv","year":"2018","journal-title":"Res."},{"issue":"6","key":"2026072914071133000_cit17","doi-asserted-by":"publisher","first-page":"2399","DOI":"10.1073\/pnas.89.6.2399","article-title":"A Major Inducer\nof Anticarcinogenic Protective Enzymes from Broccoli: Isolation and\nElucidation of Structure","volume":"89","author":"Zhang","year":"1992","journal-title":"Proc. Natl. Acad.\nSci. U.S.A."},{"issue":"2","key":"2026072914071133000_cit18","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1006\/abio.1996.0311","article-title":"Quantitative Determination\nof Isothiocyanates, Dithiocarbamates, Carbon Disulfide, and Related\nThiocarbonyl Compounds by Cyclocondensation with 1,2-Benzenedithiol","volume":"239","author":"Zhang","year":"1996","journal-title":"Anal. Biochem."},{"issue":"1","key":"2026072914071133000_cit19","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.78060","article-title":"Impact of Sulforaphane on Breast Cancer Progression\nand Radiation Therapy Outcomes: A Systematic Review","volume":"17","author":"Alhazmi","year":"2025","journal-title":"Cureus"},{"issue":"3","key":"2026072914071133000_cit20","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.3390\/ijms26031013","article-title":"Combination\nof Low-Dose Sulforaphane and Docetaxel on Mitochondrial Function and\nMetabolic Reprogramming in Prostate Cancer Cell Lines","volume":"26","author":"Pen\u0303ata-Taborda","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"2026072914071133000_cit21","doi-asserted-by":"publisher","first-page":"103543","DOI":"10.1016\/j.redox.2025.103543","article-title":"The Covalent\nModification of STAT1 Cysteines by Sulforaphane Promotes Antitumor\nImmunity via Blocking IFN-\u03b3-Induced PD-L1 Expression","volume":"81","author":"Shi","year":"2025","journal-title":"Redox Biol."},{"issue":"3","key":"2026072914071133000_cit22","doi-asserted-by":"publisher","first-page":"428","DOI":"10.3390\/nu17030428","article-title":"Protective Effects of Sulforaphane Preventing Inflammation\nand Oxidative Stress to Enhance Metabolic Health: A Narrative Review","volume":"17","author":"Alves","year":"2025","journal-title":"Nutrients"},{"key":"2026072914071133000_cit23","doi-asserted-by":"publisher","first-page":"3525","DOI":"10.1002\/jsfa.14193","article-title":"Brassica Oleracea as\na Functional Crop: Phytochemical Potential and Sustainable Applications","volume":"105","author":"Mittal","year":"2025","journal-title":"J. Sci. Food Agric."},{"key":"2026072914071133000_cit24","doi-asserted-by":"publisher","first-page":"589818","DOI":"10.3389\/fimmu.2020.589818","article-title":"Sulforaphane Promotes Dendritic Cell\nStimulatory Capacity Through Modulation of Regulatory Molecules, JAK\/STAT3-\nand MicroRNA-Signaling","volume":"11","author":"Wang","year":"2020","journal-title":"Front. Immunol."},{"key":"2026072914071133000_cit25","doi-asserted-by":"publisher","first-page":"5973","DOI":"10.12659\/MSM.908130","article-title":"Activation of the Nuclear Erythroid 2-Related Factor\n2 Antioxidant\nResponsive Element (Nrf2-ARE) Signaling Pathway Alleviates Acute Graft-Versus-Host\nDisease by Reducing Oxidative Stress and Inhibiting Infiltration of\nInflammatory Cells in an Allogeneic Stem Cell Transplantation Mouse\nModel","volume":"24","author":"Yi","year":"2018","journal-title":"Med. Sci. Monit."},{"issue":"10","key":"2026072914071133000_cit26","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1093\/chrsci\/49.10.801","article-title":"Development\nand Validation of an LC-MS-MS Method for the Simultaneous Determination\nof Sulforaphane and Its Metabolites in Rat Plasma and Its Application\nin Pharmacokinetic Studies","volume":"49","author":"Wang","year":"2011","journal-title":"J. Chromatogr. Sci."},{"issue":"12","key":"2026072914071133000_cit27","doi-asserted-by":"publisher","first-page":"2709","DOI":"10.1007\/s11095-006-9104-4","article-title":"A Review of Poloxamer\n407 Pharmaceutical and Pharmacological Characteristics","volume":"23","author":"Dumortier","year":"2006","journal-title":"Pharm. Res."},{"key":"2026072914071133000_cit28","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/978-1-4614-8993-1_13","article-title":"Poloxamers\nas Drug-Delivery Systems: Physicochemical, Pharmaceutical, and Toxicological\nAspects","volume-title":"Nanotoxicology: materials, methodologies,\nand assessments","author":"de Arau\u0301jo","year":"2014"},{"issue":"4","key":"2026072914071133000_cit29","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1007\/s12551-023-01093-2","article-title":"Poloxamer-Based\nNanogels as Delivery Systems: How Structural Requirements Can Drive\nTheir Biological Performance?","volume":"15","author":"Shriky","year":"2023","journal-title":"Biophys. Rev."},{"issue":"4","key":"2026072914071133000_cit30","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.ejps.2005.11.001","article-title":"Modulation\nof the Rheological and Mucoadhesive Properties of Thermosensitive\nPoloxamer-Based Hydrogels Intended for the Rectal Administration of\nQuinine","volume":"27","author":"Koffi","year":"2006","journal-title":"Eur. J. Pharm. Sci."},{"issue":"2","key":"2026072914071133000_cit31","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/S0378-5173(00)00615-3","article-title":"Pluronic F-127\nGels Incorporating Highly Purified Unsaturated Fatty\nAcids for Buccal Delivery of Insulin","volume":"212","author":"Morishita","year":"2001","journal-title":"Int. J.\nPharm."},{"issue":"1","key":"2026072914071133000_cit32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.colsurfb.2009.09.001","article-title":"Biodegradable\nPolymeric Nanoparticles\nBased Drug Delivery Systems","volume":"75","author":"Kumari","year":"2010","journal-title":"Colloids Surf.\nB Biointerfaces"},{"issue":"8","key":"2026072914071133000_cit33","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2017.e00390","article-title":"Thermogelling Properties of Purified\nPoloxamer 407","volume":"3","author":"Fakhari","year":"2017","journal-title":"Heliyon"},{"key":"2026072914071133000_cit34","doi-asserted-by":"publisher","first-page":"111934","DOI":"10.1016\/j.colsurfb.2021.111934","article-title":"Bioactive Glass\/Poloxamer\n407 Hydrogel Composite as\na Drug Delivery System: The Interplay between Glass Dissolution and\nDrug Release Kinetics","volume":"206","author":"Borges","year":"2021","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"2026072914071133000_cit35","first-page":"46","article-title":"Pluronic Copolymers-Characteristics, Properties, and\nPharmaceutical Applications: Part I","volume":"6","author":"Garcia Sagrado","year":"1994","journal-title":"Pharm.\nTechnol. Eur"},{"key":"2026072914071133000_cit36","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1016\/j.ijbiomac.2018.01.064","article-title":"Hyaluronic\nAcid in Pluronic F-127\/F-108 Hydrogels for Postoperative Pain in Arthroplasties:\nInfluence on Physico-Chemical Properties and Structural Requirements\nfor Sustained Drug-Release","volume":"111","author":"Nascimento","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"issue":"10","key":"2026072914071133000_cit37","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1016\/j.bjps.2007.03.005","article-title":"Hyaluronic\nAcid: The Scientific and\nClinical Evidence","volume":"60","author":"Price","year":"2007","journal-title":"J. Plast. Reconstr. Aesthet.\nSurg."},{"issue":"1","key":"2026072914071133000_cit38","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.jdermsci.2022.06.001","article-title":"Anti-Inflammatory\nEffects of Differential Molecular Weight Hyaluronic Acids on UVB-Induced\nCalprotectin-Mediated Keratinocyte Inflammation","volume":"107","author":"Hu","year":"2022","journal-title":"J. Dermatol. 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