Multileveled Hierarchical Hydrogel with Continuous Biophysical and Biochemical Gradients for Enhanced Repair of Full-thickness Osteochondral Defect.

The repair of hierarchical osteochondral defect requires sophisticated gradient reestablishment; however, few current strategies for continuous gradient casting consider the relevance to clinical practice regarding cell adaptability, multiple gradient elements, and precise gradient mirroring native tissue. Here, a hydrogel with continuous gradients in nano-hydroxyapatite (HA) content, mechanical, and magnetism are developed using synthesized superparamagnetic HA nanorods (MagHA) that easily respond to a brief magnetic field. To precisely reconstruct osteochondral tissue, we calculate the optimized gradient mode according to magnetic resonance imaging (MRI) of healthy rabbit knees. Then, MagHA are patterned to form an evidence-based gradient, consequently generating incremental HA, mechanical, and electromagnetic cues under an external magnetic stimulus from top to bottom matching cartilage-bone interface. To make such depth-dependent biocues work, an adaptable hydrogel is developed to conform to cell infiltration. Furthermore, this approach is applied in rabbit full-thickness osteochondral defects equipped with a local magnetic field. Surprisingly, this multileveled gradient hydrogel repairs osteochondral unit in a perfect heterogeneous feature, which mimics the gradual cartilage-to-subchondral transition. Collectively, this is the first study that combines an adaptable hydrogel with magneto-driven MagHA gradients to achieve promising outcomes in osteochondral regeneration. This article is protected by copyright. All rights reserved.