3D Printing Hydrogel Scaffolds with Nanohydroxyapatite Gradient to Effectively Repair Osteochondral Defects in Rats

Osteochondral (OC) defects pose an enormous challenge with no entirely satisfactory repair strategy to date. Herein, a 3D printed gradient hydrogel scaffold with a similar structure to that of OC tissue is designed, involving a pure hydrogel‐based top cartilage layer, an intermediate layer for calcified cartilage with 40% (w w−1) nanohydroxyapatite (nHA) and 60% (w w−1) hydrogel, and a 70/30% (w w−1) nHA/hydrogel‐based bottom subchondral bone layer. This study is conducted to evaluate the efficacy of the scaffold with nHA gradients in terms of its ability to promote OC defect repair. The fabricated composites are evaluated for physicochemical, mechanical, and biological properties, and then implanted into the OC defects in 56 rats. Overall, bone marrow stromal cells (BMSCs)‐loaded gradient scaffolds exhibit superior repair results as compared to other scaffolds based on gross examination, micro‐computed tomography (micro‐CT), as well as histologic and immunohistochemical analyses, confirming the ability of this novel OC graft to facilitate simultaneous regeneration of cartilage‐subchondral bone. A 3D printed nanohydroxyapatite/hydrogel composite with a gradient structure that closely matches the cartilage‐subchondral bone is prepared. With such a 3‐layer gradient structure, the scaffold can exactly match the biomedical functions of the cartilage, calcified cartilage, and subchondral bone, meanwhile, possessing the desired dimensional stability, porous microstructure, remarkable mechanical properties, appropriate degradability, and optimal in vivo repair outcomes.