Hybrid multilayer coating as the psoralen delivery vehicle promoting bone regeneration on titanium mesh scaffolds in a Posterolateral Spinal Fusion model

The instant and long-term stabilities of the implanted cage between the two vertebras are key factors for successful spinal fusion surgery. Instead of simply induce bone formation by including osteo-inductive cytokines carrying materials in the cavum of the cage, the modification of the cage surfaces to facilitate cage-bone integration yet promoting bone regeneration is becoming more essential. In this study, we used the titanium mesh scaffold (TMS) as the model cage and activated the surface with the synergism of a bone-conductive poly electrolyte multilayer film (PEM) and the bone-inductive drug psoralen (PSO). The Hyaluronic Acid/Polymerizated Dopamine modified Hydroxyapatite/Chitosan (HA/PDHA/CHI) multilayer film was constructed on the scaffold in layer-by-layer (LBL) fashion, and PSO was loaded on the scaffold via post-diffusion. SEM and FTIR confirmed the successful coating of HA/PDHA/CHI multilayer film on TMS as well as the effective loading of psoralen. The rough and porous surface structure of the hybrid PEM facilitated the proliferation and adhesion of rat bone mesenchymal stem cells (rBMSCs), and the PEM coated scaffolds exhibited advantages in PSO loading and retention. In vitro experiments demonstrated that psoralen had direct and effective osteogenic ability and the ability was closely related to the activation of the autophagy, while PEM promotes new bone formation by favoring cell proliferation and adhesion. In the Rat Model of L4-L5 Posterolateral Spinal Fusion, HA/PDHA/CHI PEM synergized with PSO greatly improved proliferation, adhesion and osteogenesis of rBMSCs, and promoted new bone formation, and therefore accelerated spinal fusion rate. This study provides a new treatment for spinal fusion therapy and may have great potential in bone regeneration and bone integration for implants.