Comparison of osteogenesis between adipose-derived mesenchymal stem cells and their sheets on poly- ϵ -caprolactone/ β -tricalcium phosphate composite scaffolds in canine bone defects

Abstract

Multipotent mesenchymal stem cells (MSCs) and MSC sheets have effective potentials of bone regeneration. Composite polymer/ceramic scaffolds such as poly-epsilon-caprolactone (PCL)/beta-tricalcium phosphate (beta-TCP) arc widely used to repair large bone defects. The present study investigated the in vitro osteogenic potential of canine adipose-derived MSCs (Ad-MSCs) and Ad MSC sheets. Composite PCL/beta-TCP scaffolds seeded with Ad-MSCs or wrapped with osteogenic Ad-MSC sheets (OCS) were also fabricated and their osteogenic potential was assessed following transplantation into critical-sized bone defects in dogs. The alkaline phosphatase (ALP) activity of osteogenic Ad-MSCs (O-MSCs) and OCS was significantly higher than that of undifferentiated AdMSCs (U-MSCs). The ALP runt-related transcription factor 2, osteopontin, and hone morphogenetic protein 7 mRNA levels were upregulated in O-MSCs and OCS as compared to U-MSCs. In a segmental hone defect, the amount of newly formed hone was greater in PCL/beta-TCP/OCS and PCL/beta-TCP/O-MSCs/OCS than in the other groups. The OCS exhibit strong osteogenic capacity, and OCS combined with a PCL/beta-TCP composite scaffold stimulated new bone formation in a critical-sized bone defect. These results suggest that the PCL/beta-TCP/OCS composite has potential clinical applications in bone regeneration and can he used as an alternative treatment modality in hone tissue engineering.