Decellularized caprine liver-derived biomimetic and pro-angiogenic scaffolds for liver tissue engineering

Abstract

The development of a pre-vascularized liver tissue construct with native-like 3-dimensional (3D) microarchitecture and extracellular matrix (ECM) composition is essential to meet the current demand for liver transplantation. Here, we report the methodology and in-depth characterization of the decellularized caprine liver scaffold (CLECM-S) for tissue engineering application. CLECM-S retained crucial ECM components and structural features similar to the native liver tissue. For comparative evaluation, conventional glutaraldehyde crosslinked collagen scaffold (Col-S) was taken as a control. CLECM-S underwent a slow but sustained swelling and collagenase mediated degradation and had the mechanical stiffness closer to that of the native human liver. HepG2 cells cultured on CLECM-S exhibited an enhanced expression of mature and functional hepatocyte markers. In addition, CLECM-S also showed pro-angiogenic properties as confirmed by Chick Chorioallantoic Membrane (CAM) assay. Upon implantation in a mouse model, the scaffolds did not elicit any significant immunogenic response. These results, together, provide a solid evidence depicting superiority of CLECM-S over conventional Col-S for liver tissue engineering applications.

Keywords: Biomimetic scaffold; Caprine liver extracellular matrix (CLECM); Decellularization; Liver; Pro-angiogenic; Tissue engineering.