In vivo remodeling of a 3D-Bioprinted tissue engineered heart valve scaffold

Abstract

To evaluate the recellularization potential of a bioprinted aortic heart valve scaffold printed with highly concentrated Type I collagen hydrogel (Lifeink® 200) and MSCs. A suspension of rat mesenchymal stem cells (MSCs) was mixed with Lifeink® 200 and was 3D-printed into gelatin support gel to produce disk scaffolds which were subsequently implanted subcutaneously in Sprague-Dawley rats for 2, 4, 8, and 12 weeks. The biomechanical properties of the scaffolds were evaluated by uniaxial tensile testing and cell infiltration and inflammation assessed via immunohistochemistry (IHC) and histological staining. There was an average decrease in both UTS and tensile modulus from 2 to 4 weeks followed by an increase between 4 to 8 weeks and a plateau from 8 to 12 weeks. IHC showed a continued expression of alpha smooth muscle actin and vimentin biomarkers throughout the study demonstrating continued presence of interstitial-like and fibroblast-like cells. Additionally, there was also an increase of elastin at each time point. The profile of the stress-strain curves of the bioprinted aortic heart valve scaffolds indicated that the scaffold transitioned through phases of resorption, synthesis, stabilization, and ultimately, remodeling. This is supported by IHC and histology which showed favorable remodeling capacity demonstrating potential feasibility for a 3D printed heart valve.