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This study investigates the decellularization of tilapia fish skin using two protocols including sodium dodecyl sulfate and sodium chloride (Treatment 1) and Triton X-100 and sodium hydroxide (Treatment 2) and evaluates their efficacy and biocompatibility. Decellularization efficiency was assessed through DNA quantification, histological analysis, and scanning electron microscopy. The DNA content in DTFS was significantly reduced (8.65\u2009\u00b1\u20091.25 ng\/mg in Treatment 1 and 18.05\u2009\u00b1\u20090.85 ng\/mg in Treatment 2) compared to native tilapia fish skin (286\u2009\u00b1\u200911 ng\/mg), confirming effective removal of cellular material. Structural integrity of ECM was preserved in both treatments. In vivo biocompatibility was assessed by implanting the native and DTFS subcutaneously in Wistar rats, followed by hematological, biochemical (Urea, ALT, ALP, and LDH), and histological analysis of skin and liver tissues over 28 days. No significant abnormalities were observed in serum parameters or tissue morphology, indicating high biocompatibility. These results support the potential use of DTFS which are biocompatible as viable wound dressing for burn and chronic wound applications.<\/jats:p>","DOI":"10.1038\/s41598-025-21808-7","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T13:12:45Z","timestamp":1761829965000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["In vivo subcutaneous biocompatibility evaluation of decellularized tilapia fish skin in a rat model"],"prefix":"10.1038","volume":"15","author":[{"given":"Swathi","family":"Borra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amrutha","family":"H. 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