Nacre-inspired magnetically oriented micro-cellulose fibres/nano-hydroxyapatite/chitosan layered scaffold enhances pro-osteogenesis and angiogenesis

In situ regeneration of large-segment bone defects is a difficult clinical problem. Here, we innovatively developed magnetically oriented micro-cellulose fibres using nano-hydroxyapatite/chitosan (CEF/Fe(3)O(4)/HA/CS) and loaded an NFκB pathway inhibitor on the surface of magnetically oriented cellulose fibres (CEF/Fe(3)O(4)/HA/CS/PQQ) prepared as a layered bioscaffold. CEF/Fe(3)O(4)/HA/CS/PQQ was constructed by layering HA/CS sheets. Nano-hydroxyapatite was deposited on the surface of cellulose fibres, then the magnetic nanoparticles on the cellulose fibres were aligned on the surface of chitosan under a magnetic field. Oriented cellulose fibres enhanced the compressive properties of the scaffold, with an average maximum compressive strength of 1.63 ​MPa. The CEF/Fe(3)O(4)/HA/CS/PQQ layered scaffold was filled into the body, and the acute inflammatory response (IL-1β and TNF-α) was suppressed through the early sustained release of PQQ. The CEF/Fe(3)O(4)/HA/CS/PQQ-layered scaffold further inhibited the osteoclasts differentiation. It was further found that the nano-hydroxyapatite on the surface of oriented cellulose fibres promoted the formation and migration of new blood vessels, accelerated the processing of collagen-I fibres to cartilage, and endochondral ossification. Hence, the development of the CEF/Fe(3)O(4)/HA/CS/PQQ layered scaffold with oriented fibres guides bone growth direction and pro-osteogenesis activity and provides a novel strategy for the in situ regeneration of large segmental bone defects.