Mesenchymal stromal cells improve the osteogenic capabilities of mineralized agarose gels in a rat full-thickness cranial defect model

Abstract

The authors previously created HAp or CaCO(3) formed on or in agarose gels (HAp and CaCO(3) gels, respectively) as biocompatible and biodegradable bone graft materials. However, these gels have limitations for bone regeneration. Mesenchymal stromal cells (MSCs) have osteogenic potential and are considered useful for bone tissue engineering. The purpose of this study was to clarify the osteogenic abilities of MSCs loaded in HAp or CaCO(3) gels (MSC/HAp and MSC/CaCO(3) gels, respectively) using a rat cranial defect model compared to HAp and CaCO(3) gels alone. HAp, CaCO(3) , MSC/Hap, and MSC/CaCO(3) gels were prepared for in vivo analyses and implanted into full-thickness bone defects created in the rat cranium. All samples were assessed radiologically and histologically at 4 and 8 weeks after implantation. Using microfocus-computed tomography, an increase in bone formation was observed in the MSC-loaded gels compared to the gels alone. In addition, peripheral quantitative computed tomography revealed higher bone mineral contents in the MSC-loaded gels compared to the gels alone. After transmission X-ray diffraction analyses, the degree of apatite c-axis orientation as a bone quality index of newly formed bone in the MSC-loaded gels was close to that of living cranial bone. Histologically, more extensive bone formation was detected in the MSC-loaded gels compared to gels alone. Overall, MSC/HAp and MSC/CaCO(3) gels showed equivalent efficacy for bone regeneration. These findings demonstrate that loading of MSCs into the gels strengthened their osteogenic ability and improved the quality of the newly formed bone. As a result, MSC-loaded gels could represent viable therapeutic biomaterials for bone tissue engineering.