Photocrosslinkable Hyaluronan-Gelatin Hydrogels for Two-Step Bioprinting

TLDR

Bioprinting is limited by the scarcity of printable biomaterials. The study introduces a novel macromonomer and a two‑step photocrosslinking strategy to enable rapid prototyping of a tubular construct. The authors synthesized methacrylated gelatin (GE‑MA) and crosslinked it with methacrylated hyaluronic acid (HA‑MA) to create an extrudable gel, then used the Fab@Home system to print a tubular construct by extruding the partially crosslinked hydrogel and re‑irradiating it to solidify the structure. The resulting HA‑MA:GE‑MA hydrogels were biocompatible, supported cell attachment and proliferation, elicited no inflammatory response in vivo, and enabled viable, ECM‑remodeling cells in a printed tubular construct, demonstrating a printable hydrogel for tissue engineering.

Abstract

Bioprinting by the codeposition of cells and biomaterials is constrained by the availability of printable materials. Herein we describe a novel macromonomer, a new two-step photocrosslinking strategy, and the use of a simple rapid prototyping system to print a proof-of-concept tubular construct. First, we synthesized the methacrylated ethanolamide derivative of gelatin (GE-MA). Second, partial photochemical cocrosslinking of GE-MA with methacrylated hyaluronic acid (HA-MA) gave an extrudable gel-like fluid. Third, the new HA-MA:GE-MA hydrogels were biocompatible, supporting cell attachment and proliferation of HepG2 C3A, Int-407, and NIH 3T3 cells in vitro. Moreover, hydrogels injected subcutaneously in nude mice produced no inflammatory response. Fourth, using the Fab@Home printing system, we printed a tubular tissue construct. The partially crosslinked hydrogels were extruded from a syringe into a designed base layer, and irradiated again to create a firmer structure. The computer-driven protocol was iterated to complete a cellularized tubular construct with a cell-free core and a cell-free structural halo. Cells encapsulated within this printed construct were viable in culture, and gradually remodeled the synthetic extracellular matrix environment to a naturally secreted extracellular matrix. This two-step photocrosslinkable biomaterial addresses an unmet need for printable hydrogels useful in tissue engineering.