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[Display omitted] Various modifications have been performed on biomaterials to improve their applications in tissue engineering and regenerative medicine. However, the challenges of immunogenicity and biocompatibility existed since the application of biomaterials. As a method to solve this problem, the decellularization process removes most living cells from biomaterials to minimize their immunogenicity; and preserves the native structures and compositions that favour cell growth and the subsequent construction of functional tissue. On the other hand, genetic modification of biomaterials aims to achieve specific functions (low immunogenicity, osteogenesis, etc.) or analyse the genetic mechanisms underlying some diseases (cardiac dysfunction, liver fibrosis, etc.). The combination of decellularization and gene modification is highly superior to biomaterials; thus, we must obtain a deeper understanding of these novel biomaterials. In this review, we summarize the fabrication approaches and current applications of genetically modified decellularized biomaterials and then discuss their disadvantages and corresponding future perspectives. [ABSTRACT FROM AUTHOR]