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Oral formulation of Wnt inhibitor complex reduces inflammation and fibrosis in intraperitoneal implants in vivo. | LitMetric

AI Article Synopsis

  • The study explores the challenges of using implantable biomaterials, which can trigger inflammation and fibrosis, leading to their eventual failure and removal.
  • It focuses on the Wnt signaling pathway's role in the healing process and tests a Wnt inhibitor (CD:LGK974) to mitigate these adverse effects.
  • Results showed that CD:LGK974 effectively reduced inflammation, collagen production, and blood vessel formation around the implants, suggesting it could improve the longevity and functionality of biomaterials in clinical settings.

Article Abstract

The use of implantable biomaterials to replace physiological and anatomical functions has been widely investigated in the clinic. However, the selection of biomaterials is crucial for long-term function, and the implantation of certain biomaterials can cause inflammatory and fibrotic processes, triggering a foreign body reaction that leads to loss of function and consequent need for removal. Specifically, the Wnt signaling pathway controls the healing process of the human body, and its dysregulation can result in inflammation and fibrosis, such as in peritoneal fibrosis. Here, we assessed the effects of daily oral administration of a Wnt pathway inhibitor complex (CD:LGK974) to reduce the inflammatory, fibrotic, and angiogenic processes caused by intraperitoneal implants. CD:LGK974 significantly reduced the infiltration of immune cells and release of inflammatory cytokines in the implant region compared to the control groups. Furthermore, CD:LGK974 inhibited collagen deposition and reduced the expression of pro-fibrotic α-SMA and TGF-β1, confirming fibrosis reduction. Finally, the CD:LGK974 complex decreased VEGF levels and both the number and area of blood vessels formed, suggesting decreased angiogenesis. This work introduces a potential new application of the Wnt inhibitor complex to reduce peritoneal fibrosis and the rejection of implants at the intraperitoneal site, possibly allowing for longer-term functionality of existing clinical biomaterials.

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Source
http://dx.doi.org/10.1007/s13346-023-01303-0DOI Listing

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