A hybrid 3D-printed aspirin-laden liposome composite scaffold for bone tissue engineering

Abstract

Bone defects are some of the most difficult injuries to treat in clinical medicine. Evidence from cellular and animal studies suggests that aspirin exhibits protective effects on bone by promoting both the survival of osteoblast precursor stem cells and osteoblast differentiation. However, acquired resistance to aspirin and its cytotoxicity significantly limit its therapeutic application. Controlled release systems have been confirmed to promote the efficacy of certain drugs for bone regeneration. Additionally, the controlled release of a high dose of drug allows for lower dosing over an extended period. In this way, nano-liposomal encapsulation of aspirin can be used to reduce the cytotoxicity of the overall dose. Using a series of osteogenic experiments, this study found that an aspirin-laden liposome delivery system (Asp@Lipo) obviously promoted osteogenesis and immunomodulation of human mesenchymal stem cells (hMSCs). We also studied the in vitro capacity of polycaprolactone (PCL)-based bioactive composite (PCL-Asp@Lipo) scaffolds to facilitate cell proliferation and osteoblast differentiation. Compared to a common scaffold, ALP assays, immunofluorescence and calcium mineralisation studies revealed that the PCL-Asp@Lipo scaffolds enhanced the osteogenic differentiation of hMSCs. Subsequently, along with the cells, PCL and PCL-Asp@Lipo scaffolds were both implanted subcutaneously into nude mice for estimation of osteo-inductivity after 6 weeks, the PCL-Asp@Lipo composite scaffold exhibited more osteogenic activity than the bare PCL scaffold. This approach has potential applications in bone tissue repair and regenerative medicine.