Smurf1-targeting miR-19b-3p-modified BMSCs combined PLLA composite scaffold to enhance osteogenic activity and treat critical-sized bone defects

Abstract

Over the past few years, tissue-engineering technology provided a new direction for bone defects therapy, which involved developing applicable biological materials composite with seed cells to repair bone defects tissue. However, as one of the commonest seed cells for tissue engineering, BMSCs (bone marrow mesenchymal stem cells), are still lacking an efficient and accurate differentiation ability into functional osteoblast. Given these facts, the development of a novel tissue engineering technology integrated BMSCs and scaffold materials have become an urgent need for bone defects repair. In this work, we found that miR-19b-3p could suppress the expression of Smurf1 which is a negative regulator of osteogenesis. By employing lentivirus pLVTHM-miR-19b-3p transfected BMSCs, we verified that miR-19b-3p could promote BMSCs osteogenic differentiation via suppressing Smurf1 expression. Furthermore, we designed a new porous PLLA/POSS scaffold combined with BMSCs for tissue engineering. In vitro experiment showed that miR-19b-3p modified BMSCs facilitated the expansion and proliferation of BMSCs when culturing with the PLLA/POSS scaffold. We established rats calvarial critical-sized defect model, after transplanting the BMSCs/PLLA/POSS for 3 month, the pathology, immunohistochemical and Micro-CT results showed that miR-19b-BMSCs/PLLA/POSS significantly facilitated the osteogenesis differentiation, enhanced the bone density of defect area and accelerated the repair of bone defect. We elucidated the mechanism that miR-19b-3p suppressed the expression of Smurf1 and provided a novel tissue engineering strategy for using microRNA gene-modified BMSCs combined with PLLA/POSS scaffold in bone tissue engineering.