ArticleFrontiers in immunology2025
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.
Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: 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. Methods: 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&E, Masson's trichrome), immunohistochemistry for CD31, VEGF, the pro-inflammatory cytokines IL-6 and TNF-α, and immunofluorescence staining for the antioxidant enzymes catalase (CAT) and superoxide dismutase 1 (SOD1) were performed on days 4, 7, 14, and 21. Results: 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<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-α 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. Conclusion: 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.
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