3D printed gelatin/hydroxyapatite scaffolds for stem cell chondrogenic differentiation and articular cartilage repair

Acute injury of the articular cartilage can lead to chronic disabling conditions because of the limited self-repair capability of the cartilage. Implantation of stem cells at the injury site is a viable treatment, but requires a scaffold with a precisely controlled geometry and porosity in the 3D space, high biocompatibility, and the capability of promoting chondrogenic differentiation of the implanted stem cells. Here we report the development of gelatin/hydroxyapatite (HAP) hybrid materials by microextrusion 3D bioprinting and enzymatic cross-linking as the scaffold for human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs). The scaffold supports the adhesion, growth, and proliferation of hUCB-MSCs and induces their chondrogenic differentiation in vitro. Doping HAP in the gelatin scaffold increases the fluidity of the hydrogel, improves the gelation kinetics and the rheological properties, and allows better control over 3D printing. Implanting the hUCB-MSC-laden scaffold at the injury site of the articular cartilage effectively repairs the cartilage defects in a pig model. Altogether, this work demonstrates the 3D printing of gelatin-based scaffold materials for hUCB-MSCs to repair cartilage defects as a potential treatment of articular cartilage injury.