Avaliação de processo inflamatório, fibrótico e angiogênico em implantes intraperitoneais de animais tratados com complexo inibidor da via Wnt

Abstract

The use of implantable biomaterials to replace physiological and anatomical functions has been widely investigated in the clinic. The selection of biomaterials capable of interacting with biological systems is crucial for long term function of the implant. The implantation of the biomaterial in the body can lead to the development of an inflammatory and fibrotic process that triggers a foreign body reaction, leading to loss of function and its consequent need for removal. Wnt signaling is one of the routes involved in the human body's healing process, and when it is dysregulated, it can contribute to the inflammatory and fibrotic processes, such as in the peritoneal fibrosis. Here, we report the use of a Wnt pathway inhibitor complex (CD:LGK974) to reduce inflammatory, fibrotic and angiogenic processes in intraperitoneal implants in vivo. We assessed the effects of oral administration of CD:LGK974 to inhibit the inflammatory, fibrotic and angiogenic processes in intraperitoneal implants. CD:LGK974 significantly reduced immune cells and inflammatory cytokines in the implant region compared to the control groups. Furthermore, CD:LGK974 inhibited the collagen deposition and reduced the expression of α-SMA, and TGF-β1, indicating the reduction of fibrosis. Finally, CD:LGK974 also decreased the number of blood vessels formed and VEGF, suggesting decreased angiogenesis. Thus, our work introduces a potentially new application of the Wnt inhibitor complex to reduce peritoneal fibrosis and rejection of implants in the intraperitoneal site.