Nacre-mimetic hydroxyapatite/chitosan/gelatin layered scaffolds modifying substance P for subchondral bone regeneration

Nacre, exhibiting excellent mechanical strengths due to its hierarchical structures, becomes a potential model to design bone implants. Herein, we firstly fabricated nacre-mimetic hydroxyapatite/chitosan/gelatin (HA/CS/Gel) layered scaffolds and incorporated substance P (SP) peptides. The CS scaffolds with a layered architecture could regulate the deposition of HA nanoplates on the interlamellar CS sheets by using CaCO 3 as precursors. The HA/CS/Gel layered scaffolds exhibited a great flexure strength of 11.42 MPa due to a brick-and-mortar structure. The biocompatible components, layered macropores and SP peptides in the HA/CS/Gel therapeutic scaffolds facilitated the spreading and proliferation mesenchymal stem cells (MSCs). Notably, the incorporation of SP peptides induced MSC osteogenic differentiation and extracellular matrix mineralization . Rabbit knee subchondral defect models further proved that the HA/CS/Gel-SP layered scaffolds promoted in vivo subchondral bone regeneration . Hence, the combination of nacre-mimetic bone implants and therapeutic drugs may become an attractive strategy for subchondral bone regeneration.