Polydopamine regulated hydroxyapatite microspheres grown in the three-dimensional honeycomb-like mollusk shell-derived organic template for osteogenesis.

Layered osteochondral composite scaffolds are considered as a promising strategy for the treatment of osteochondral defects. However, the insufficient osseous support and integration of the subchondral bone layer frequently result in the failure of osteochondral repair. Therefore, it is essentially important to explore new subchondral bone constructs tailored to support bone integration and healing. In this study, a novel three-dimensional porous biomimetic construct (HA/pDA-OTMS) was successfully developed by polydopamine (pDA) regulating hydroxyapatite (HA) microspheres grown in the honeycomb-like mollusk shell-derived organic template (OTMS). The biomimetic OTMS had good mechanical properties, high toughness, biodegradability and excellent biocompatibility. Moreover, the long-range ordered cavity structure of OTMS allowed the smallest material to create the largest and most stable geometric space, endowing it high HA loading capacity. The modification of pDA on OTMS surface effectively promoted the mineral nucleation of HA in the micro-nano cavities of OTMS. The compression mechanical tests showed that the combination of inorganic HA and organic pDA-OTMS greatly improved the mechanical properties of the construct. Additionally, the HA/pDA-OTMS composite provided adequate 3-D support for osteoblast cell attachment, proliferation and differentiation, as well as significantly up-regulated the expression of osteogenesis-related genes. These results demonstrated that as-prepared HA/pDA-OTMS constructs with combined mechanical strength and excellent osteogenic activity show great application prospects in subchondral bone regeneration.