Catechol functionalized ink system and thrombin-free fibrin gel for fabricating cellular constructs with mechanical support and inner micro channels

Abstract

The development of 3D bio printing technology has contributed to protocols for the repair and regeneration of tissues in recent years. However, it is still a great challenge to fabricate structures that mimic the complexity of native tissue, including both the biomechanics and microscale internal structure. In this study, a catechol functionalized ink system was developed to produce tough and elastic scaffolds with built-in micro channels that simulate the vascular structure. And a skin model was designed to evaluate the cytocompatibility of the scaffolds. The mechanical support stemmed from the double network based on catechol-hyaluronic acid (HACA) and alginate, the micro channels were generated using sacrificial gelatin. HACA/alginate and gelatin were firstly printed using a 3D extrusion printer. Thrombin-free fibrinogen were then mixed with human dermal fibroblasts and introduced to the printed scaffolds to induce gelation. An immortal human keratinocyte cell line was introduced on top of the cellular construct to mimic the full thickness skin structure. The printed scaffolds demonstrated high elasticity and supported the formation of a double-layered cell-laden skin like structure. The results suggest the 3D printing platform developed here provides a platform for skin regeneration and could be explored further to engineer functional skin tissue by incorporation of other types of cells.