{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:22:06Z","timestamp":1788268926369,"version":"build-2803163510"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Deep second-degree burns impair skin regeneration and carry high risks of scarring and infection. Achieving healing with minimal immune rejection remains challenging. Platelet-rich fibrin (PRF), an autologous biomaterial, promotes angiogenesis and repair via sustained growth factor release. CTLA4Ig, an immunomodulatory agent, can suppress T-cell-mediated rejection. We hypothesized that combining PRF with CTLA4Ig gene-transfected porcine skin would synergistically enhance wound healing by concurrently stimulating regeneration and modulating local immunity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A standardized deep second-degree burn was created on the dorsum of 32 Sprague-Dawley rats, randomly divided into four groups (n=8): Vaseline group, PRF group, Pigskin group, and PRF+pigskin group. Wound closure was tracked macroscopically for 21 days. Histological analysis (H&amp;amp;E, Masson\u2019s trichrome), immunohistochemistry for CD31, VEGF, the pro-inflammatory cytokines IL-6 and TNF-\u03b1, and immunofluorescence staining for the antioxidant enzymes catalase (CAT) and superoxide dismutase 1 (SOD1) were performed on days 4, 7, 14, and 21.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The combination treatment (PRF+pigskin group) demonstrated a significant acceleration in wound closure compared to all other groups, with near-complete re-epithelialization observed by day 14. Statistical analysis confirmed a significant interaction between Treatment and Time (p&amp;lt;0.001), suggesting a synergistic healing pattern. Histological examination revealed more organized and dense collagen fibers, with the most pronounced effect in PRF+pigskin group. Immunohistochemical and immunofluorescence analyses indicated a marked upregulation of CD31-positive vessels, VEGF expression, and antioxidant enzymes (CAT and SOD1) in the combination group, indicating a trend towards enhanced angiogenesis and an augmented capacity to mitigate oxidative stress. Concurrently, immunohistochemistry for IL-6 and TNF-\u03b1 revealed a significant attenuation of these pro-inflammatory cytokines in the PRF+pigskin group and the pigskin group, particularly at the later stages of healing (D14, D21), indicating a modulation of the local inflammatory response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The concomitant application of PRF and CTLA4Ig gene-transfected porcine skin suggests a synergistic effect, creating a pro-regenerative, immunomodulatory, anti-inflammatory, and antioxidative microenvironment. This resulted in significantly accelerated and improved healing of deep second-degree burn wounds, representing a promising and innovative therapeutic paradigm for the management of severe burns.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1756818","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T06:32:33Z","timestamp":1768804353000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Synergistic effects of platelet-rich fibrin and CTLA4Ig gene-transfected porcine skin on accelerating wound healing in a rat model of deep second-degree burns: a mechanistic study"],"prefix":"10.3389","volume":"16","author":[{"given":"Jiliang","family":"Li","sequence":"first","affiliation":[{"name":"Burn Department, Ningbo No. 2 Hospital","place":["Ningbo, Zhejiang, 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