Ameliorating Effects of the Hydrogel-Stem Cell-Melatonin Combination with or Without a Mesh to Treat Experimentally Induced Liver Degeneration in Rats

Abstract

Objectives: This study aimed to investigate the therapeutic efficacy of a hydrogel loaded with Wharton's Jelly mesenchymal stem cells (WJ-MSCs) and melatonin, administered to the liver either via mesh-hydrogel implantation or intraperitoneal hydrogel injection, in a thioacetamide (TAA)-induced liver fibrosis animal model. Methods: A collagen-based hydrogel containing WJ-MSCs and melatonin was prepared for injection as well as combined with electrospun mesh for implantation. Hydrogel and mesh were characterized with respect to morphology, degradation, and mechanical properties. In in vivo studies, liver fibrosis was induced in rats by intraperitoneal injection of TAA for 6 weeks. After fibrosis induction, animals received either hydrogel injection or implantation of the combined construct. After 21 days, serum and liver tissues were collected, and biochemical, histopathological, and ultrastructural analyses were performed through comparative evaluation of experimental groups. Results: SEM results demonstrated that hydrogel, with appropriate porosity, was well integrated with the mesh without any detachment. The mesh, composed of submicron-scale fibers, exhibited a Young's modulus of 10.37 +/- 2.33 MPa. The hydrogel presented a degradation profile with a 40% mass loss in 24 h, reaching approximately 50% by day 30. Biochemical results indicated significant improvement in liver regeneration with both treatment strategies, particularly with the implanted construct. Histopathological analysis revealed decreased inflammation and hepatocyte vacuolization following both treatments; however, collagen accumulation was significantly reduced in the implant group. Ultrastructural analysis showed preserved nuclear integrity and reduced endoplasmic reticulum dilation and degenerative changes in implant group. Conclusions: The combination of WJ-MSCs and melatonin-loaded hydrogel with supportive mesh particularly enhanced tissue regeneration in liver fibrosis.