Development and Biocompatibility Assessment of Decellularized Porcine Uterine Extracellular Matrix-Derived Grafts

Biomaterials derived from biological matrices have been widely investigated due to their great therapeutic potential in regenerative medicine, since they are able to induce cell proliferation, tissue remodeling, and angiogenesis in situ. In this context, highly vascularized and proliferative tissues, such as the uterine wall, present an interesting source to produce acellular matrices that can be used as bioactive materials to induce tissue regeneration. Therefore, this study aimed to establish an optimized protocol to generate decellularized uterine scaffolds (dUT), characterizing their structural, compositional, and biomechanical properties. In addition, in vitro performance and in vivo biocompatibility were also evaluated to verify their potential applications for tissue repair. Results showed that the protocol was efficient to promote cell removal, and dUT general structure and extracellular matrix composition remained preserved compared with native tissue. In addition, the scaffolds were cytocompatible, allowing cell growth and survival. In terms of biocompatibility, the matrices did not induce any signs of immune rejection in vivo in a model of subcutaneous implantation in immunocompetent rats, demonstrating an indication of tissue integration after 30 days of implantation. In summary, these findings suggest that dUT scaffolds could be explored as a biomaterial for regenerative purposes, which is beyond the studies in the reproductive field. Impact Statement Extracellular matrix-derived biomaterials have been explored as a powerful tool to develop new therapeutic approaches for tissue repair. The development of novel methods to produce well-structured biocompatible scaffolds is essential for their further application, once their bioactivity is directly related to regenerative properties. Considering that the uterine extracellular matrix is an important component of the endometrial microenvironment, which is highly proliferative and angiogenic, this study aimed to establish an optimized protocol to generate porcine uterine scaffolds, demonstrating their structural and functional properties, which can support their application in further regenerative medicine studies.