Early obstruction of decellularized xenogenic valves in pediatric patients: involvement of inflammatory and fibroproliferative processes

Abstract 

Background

Decellularization of pulmonary valve substitutes is believed to eliminate immunogenicity and improve conduit durability. This study focused on a detailed histopathological and immunohistochemical analysis of explanted Matrix P plus valves, following their early obstruction in pediatric patients.

Methods

Occurrence of fibrosis, scar formation, neovascularization, and inflammatory infiltrates were determined in longitudinal sections of four valve specimens explanted after 12–15 months. Valves were immunohistochemically analyzed for presence of different subtypes of inflammatory cells. The expression of smooth muscle actin and connective tissue growth factor was determined.

Results

We observed a foreign body-type reaction accompanied by severe fibrosis and massive neointima formation around decellularized porcine valve wall, whereas the equine pericardial patch remained separated from porcine layer and acellular. Re-cellularization of decellularized matrix was low, and neovascularization was observed only in the neointima and scar tissue. Inflammatory infiltrates, composed mainly of T cells, B cells, and plasma cells, as well as the presence of dendritic cells, macrophages, and mast cells were detected in the tissue surrounding the porcine matrix. In the fibrous tissue, overexpression of connective tissue growth factor was observed. The leaflets remained functional, with normal endothelialization and no degenerative changes. Control pre-implant samples of Matrix P plus valve revealed incomplete decellularization of porcine matrix, which may have contributed to increased immunogenicity of these conduits.

Conclusions

Early obstruction of decellularized Matrix P plus valve is associated with massive inflammatory reaction and exaggerated fibrotic scaring around porcine conduit wall. Detailed studies will be necessary to determine factors that contribute to remnant immunogenicity of decellularized grafts.

Keywords: Decellularized xenograft, Pulmonary valve replacement, Fibrosis, Neointima formation, Inflammation