Tissue Remodeling of Engineered Valved Conduit Evaluated at 52 Weeks in the Growing Lamb

Abstract

Objective: Tissue-engineered valved conduits that can resist calcification and degradation while allowing somatic growth would provide an ideal solution for congenital valve replacement. The goal of this study was to assess remodeling of conduits made from acellular engineered matrix manufactured from allogeneic fibroblasts. Methods: Three 16mm diameter tubes of engineered tissue were stitched together with Maxon degradable sutures to create a novel tri-leaflet valved conduit. The valved conduit was implanted as a pulmonary replacement in 7 lambs (average age 15.5 wk) up to 12 months. Conduits explanted after 12 - 52 weeks were evaluated histologically and biochemically for matrix remodeling and calcification. Results: The valved conduits explanted at the earliest timepoint of 12 weeks showed degradation of Maxon sutures indicating matrix remodeling was providing the load-bearing properties at resorbing suture lines. The conduit increased in diameter over the implant duration. Collagen and protein concentrations in the wall of the conduit at 52 weeks were increased. Histology showed recellularization of the wall matrix with αSMA+ interstitial cells and CD31+ endothelial cells on the lumen surface. The leaflet matrix showed no change in the collagen or protein concentration compared to the implant. The cell concentration in the leaflet matrix increased from zero at implant to 34±10M cells/cm3 at the 52 week explant. Cells on the leaflet surface were also CD31+. Von Kossa stain showed no calcification other than near Maxon sutures and sparse punctate micro-calcification in two valves. Conclusions: This 1-yr study of a valved conduit implanted in a growing lamb demonstrated extensive matrix remodeling both to provide load-bearing capabilities at the degradable suture lines and new extracellular matrix to confer somatic growth. Combined with a lack of macro-calcification over the 1-yr implantation are promising outcomes to support the use of this acellular engineered matrix for potential pediatric use.