In Situ Crosslinkable Collagen-Based Hydrogels for 3D Printing of Dermis-Mimetic Constructs

Abstract

Recently, several three-dimensional (3D) bioprinting techniques have emerged for the synthesis of 3D tissue analogs. Accordingly, many researchers have focused on the development of novel bioinks that can mimic the natural extracellular matrix with cytocompatibility and biofunctionality. Hyaluronic acid and collagen are the most abundant proteins in the extracellular matrix of the skin and are known to support several cellular behaviors. Herein, we developed tyramine-conjugated hyaluronic acid and collagen (HA-Tyr/Col-Tyr) hydrogel bioinks, which are photocrosslinkable in the presence of riboflavin and ammonium peroxydisulfate, to fabricate dermis-mimetic constructs. The physicochemical properties and 3D printability of the HA-Tyr/Col-Tyr hydrogel were examined. 3D printing of the lattice structure with the HA-Tyr/Col-Tyr hydrogel enabled a sophisticated micron-sized fine structure without any clogging or coagulation. Approximately 80% of normal human dermal fibroblasts (NHDFs) in the printed constructs were alive after 24 h of culture. Moreover, the 3D printed constructs supported 4.57-fold cell proliferation and 4.23-fold f-actin expansion over four days in culture, indicating that HA-Tyr/Col-Tyr hydrogels provide cytocompatible microenvironments. The findings of this study suggest that HA-Tyr/Col-Tyr hydrogels are promising candidates as bioinks for the 3D printing of dermis-mimetic constructs.