Polydopamine-coated biomimetic bone scaffolds loaded with exosomes promote osteogenic differentiation of BMSC and bone regeneration.

Introduction: The repair of bone defects is ideally accomplished with bone tissue engineering. Recent studies have explored the possibility of functional modification of scaffolds in bone tissue engineering. We prepared an SF-CS-nHA (SCN) biomimetic bone scaffold and functionally modified the scaffold material by adding a polydopamine (PDA) coating loaded with exosomes (Exos) of marrow mesenchymal stem cells (BMSCs). The effects of the functional composite scaffold (SCN/PDA-Exo) on BMSC proliferation and osteogenic differentiation were investigated. Furthermore, the SCN/PDA-Exo scaffolds were implanted into animals to evaluate their effect on bone regeneration.

Methods: SCN biomimetic scaffolds were prepared by a vacuum freeze-drying/chemical crosslinking method. A PDA-functionalized coating loaded with BMSC-Exos was added by the surface coating method. The physical and chemical properties of the functional composite scaffolds were detected by scanning electron microscopy (SEM), energy spectrum analysis and contact angle tests. In vitro, BMSCs were inoculated on different scaffolds, and the Exo internalization by BMSCs was detected by confocal microscopy. The BMSC proliferation activity and cell morphology were detected by SEM, CCK-8 assays and phalloidin staining. BMSC osteogenic differentiation was detected by immunofluorescence, alizarin red staining and qRT‒PCR. In vivo, the functional composite scaffold was implanted into a rabbit critical radial defect model. Bone repair was detected by 3D-CT scanning. HE staining, Masson staining, and immunohistochemistry were used to evaluate bone regeneration.

Results: Compared with the SCN scaffold, the SCN/PDA-Exo-functionalized composite scaffold had a larger average surface roughness and stronger hydrophilicity. In vitro, the Exos immobilized on the SCN/PDA-Exo scaffolds were internalized by BMSCs. The BMSC morphology, proliferation ability and osteogenic differentiation effect in the SCN/PDA-Exo group were significantly better than those in the other control groups (p < 0.05). The effects of the SCN/PDA-Exo functional composite scaffold on bone defect repair and new bone formation were significantly better than those of the other control groups (p < 0.05).

Conclusions: In this study, we found that the SCN/PDA-Exo-functionalized composite scaffold promoted BMSC proliferation and osteogenic differentiation in vitro and improved bone regeneration efficiency in vivo. Therefore, combining Exos with biomimetic bone scaffolds by functional PDA coatings may be an effective strategy for functionally modifying biological scaffolds.