A coaxial electrospun mat coupled with piezoelectric stimulation and atorvastatin for rapid vascularized bone regeneration

Abstract

The repair of critical bone defects caused by various clinical conditions needs to be addressed urgently, and the regeneration of large bone defects depends on early vascularization. Therefore, enhanced vascularization of artificial bone grafts may be a promising strategy for the regeneration of critical-sized bone defects. Taking into account the importance of rapid angiogenesis during bone repair and the potential of piezoelectric stimulation in promoting bone regeneration, novel coaxial electrospun mats coupled with piezoelectric materials and angiogenic drugs were fabricated in this study using coaxial electrospinning technology, with a shell layer loaded with atorvastatin (AVT) and a core layer loaded with zinc oxide (ZnO). AVT was used as an angiogenesis inducer, and piezoelectric stimulation generated by the zinc oxide was used as an osteogenesis enhancer. The multifunctional mats were characterized in terms of morphology, core–shell structure, piezoelectric properties, drug release, and mechanical properties, and their osteogenic and angiogenic capabilities were validated in vivo and ex vivo. The results revealed that the coaxial electrospun mats exhibit a porous surface morphology and nanofibers with a core–shell structure, and the piezoelectricity of the mats improved with increasing ZnO content. Excellent biocompatibility, hydrophilicity and cell adhesion were observed in the multifunctional mats. Early and rapid release of AVT in the fibrous shell layer of the mat promoted angiogenesis in human umbilical vascular endothelial cells (HUVECs), whereas ZnO in the fibrous core layer harvested bioenergy and converted it into electrical energy to enhance osteogenic differentiation of rat bone mesenchymal stem cells (BMSCs), and both modalities synergistically promoted osteogenesis and angiogenesis. Furthermore, optimal bone regeneration was achieved in a model of critical bone defects in the rat mandible. This osteogenesis-promoting effect was induced by electrical stimulation via activation of the calcium signaling pathway. This multifunctional mat coupling piezoelectric stimulation and atorvastatin promotes angiogenesis and bone regeneration, and shows great potential in the treatment of large bone defects.