Preparation and characterization of photocurable composite extracellular matrix-methacrylated hyaluronic acid bioink

Abstract

Producing a bioink that fulfills the physicochemical requirements of printing and provides a desirable environment for encapsulated cells is a major challenge in three-dimensional (3D) bioprinting. Thus, we have developed a biocompatible bioink (ECM@MeHA bioink) with suitable mechanical support and visible light printable properties. In this bioink system, the thermosensitive extracellular matrix (ECM) was prepared and can be crosslinked at 37 °C. And the prepared methacrylated hyaluronic acid (MeHA) can be crosslinked under visible light using the biosafe initiators (Eosin Y, TEOA, and NVP). Thus, the ECM@MeHA bioink consisted of a mix solution of ECM and MeHA containing visible light initiators can cure at 515 nm visible light for 30 s and then further crosslinked at 37 °C to form a double network hydrogel. Then, the mechanical properties and biocompatibility of ECM@MeHA hydrogel, and the printability and the cell viability of the ECM@MeHA bioink were systemically evaluated. The results showed that the mechanical property of the MeHA hydrogel is significantly improved following the addition of 10 mg mL⁻¹ of ECM (10ECM@MeHA). The compressive strength and modulus of 10ECM@MeHA hydrogel were 102.38 ± 5.27 kPa and 782 ± 20.36 kPa, which were 2.7 times and 3.1 times higher than those of MeHA, respectively. After encapsulating MC3T3-E1 cells in the 10ECM@MeHA hydrogel for 7 days, the culture showed excellent biocompatibility. The 10ECM@MeHA bioink and cell–laden 10ECM@MeHA bioink were printed, and the cells were successfully encapsulated by the extrusion-based bioprinting and digital light processing (DLP) -based bioprinting. The cell–laden 10ECM@MeHA scaffold showed 94.27 ± 3.00% cell viability after 7 days of the 3D culture. In conclusion, 10ECM@MeHA bioink may provide a new strategy for constructing disease models or drug screening models in vitro and is expected to be widely used in the field of tissue engineering scaffolds.