Effect of Different Bone Grafting Materials and Mesenchymal Stem Cells on Bone Regeneration: A Micro-Computed Tomography and Histomorphometric Study in a Rabbit Calvarial Defect Model.

Shiau-Ting Shiu,Wei-Fang Lee,Pin-Chuang Lai,Liu-Ting Hao,Sheng-Wei Feng,Sheng-Min Chen,Yuan-Ting Hung

doi:10.3390/ijms22158101

Abstract

This study evaluated the new bone formation potential of micro–macro biphasic calcium phosphate (MBCP) and Bio-Oss grafting materials with and without dental pulp-derived mesenchymal stem cells (DPSCs) and bone marrow-derived mesenchymal stem cells (BMSCs) in a rabbit calvarial bone defect model. The surface structure of the grafting materials was evaluated using a scanning electron microscope (SEM). The multipotent differentiation characteristics of the DPSCs and BMSCs were assessed. Four circular bone defects were created in the calvarium of 24 rabbits and randomly allocated to eight experimental groups: empty control, MBCP, MBCP+DPSCs, MBCP+BMSCs, Bio-Oss+DPSCs, Bio-Oss+BMSCs, and autogenous bone. A three-dimensional analysis of the new bone formation was performed using micro-computed tomography (micro-CT) and a histological study after 2, 4, and 8 weeks of healing. Homogenously porous structures were observed in both grafting materials. The BMSCs revealed higher osteogenic differentiation capacities, whereas the DPSCs exhibited higher colony-forming units. The micro-CT and histological analysis findings for the new bone formation were consistent. In general, the empty control showed the lowest bone regeneration capacity throughout the experimental period. By contrast, the percentage of new bone formation was the highest in the autogenous bone group after 2 (39.4% ± 4.7%) and 4 weeks (49.7% ± 1.5%) of healing (p < 0.05). MBCP and Bio-Oss could provide osteoconductive support and prevent the collapse of the defect space for new bone formation. In addition, more osteoblastic cells lining the surface of the newly formed bone and bone grafting materials were observed after incorporating the DPSCs and BMSCs. After 8 weeks of healing, the autogenous bone group (54.9% ± 6.1%) showed a higher percentage of new bone formation than the empty control (35.3% ± 0.5%), MBCP (38.3% ± 6.0%), MBCP+DPSC (39.8% ± 5.7%), Bio-Oss (41.3% ± 3.5%), and Bio-Oss+DPSC (42.1% ± 2.7%) groups. Nevertheless, the percentage of new bone formation did not significantly differ between the MBCP+BMSC (47.2% ± 8.3%) and Bio-Oss+BMSC (51.2% ± 9.9%) groups and the autogenous bone group. Our study results demonstrated that autogenous bone is the gold standard. Both the DPSCs and BMSCs enhanced the osteoconductive capacities of MBCP and Bio-Oss. In addition, the efficiency of the BMSCs combined with MBCP and Bio-Oss was comparable to that of the autogenous bone after 8 weeks of healing. These findings provide effective strategies for the improvement of biomaterials and MSC-based bone tissue regeneration.

Highlights

Tissue engineering involves the application of biological and engineering principles for the repair and functional enhancement of human tissues [1]
The present study comprehensively evaluated healing capacities of synthetic bone grafting materials (micro–macro biphasic calcium the bone healing capacities of synthetic bone grafting materials (micro–macro biphasic phosphate (MBCP)) and xenografts (Bio-Oss) with and without DPSCs and bone marrow-derived mesenchymal stem cells (BMSCs) comcalcium phosphate (MBCP)) and xenografts (Bio-Oss) with and without DPSCs and BMpared with an empty defect and the autogenous bone in a rabbit calvarial bone defect
An increased number of osteoblastic cells lining the surface of the newly formed bone and bone grafting materials were observed after incorporating the Mesenchymal stem cells (MSCs). These findings demonstrated that both the DPSCs and BMSCs enhanced the osteoconductive capacities of macro biphasic calcium phosphate (MBCP) and Bio-Oss

Summary

Introduction

Tissue engineering involves the application of biological and engineering principles for the repair and functional enhancement of human tissues [1]. For the reconstruction of craniofacial bone defects, interdisciplinary methods and concepts, including the use of suitable scaffold materials, feasible seed cells, secretome, and bioactive factors, are considered to be vital in the field of bone regeneration [2,3,4,5,6,7]. The autogenous bone is considered the gold standard for the reconstruction of bone defects, several disadvantages limit its clinical application, including the morbidity of the potential donor site, the requirement of additional surgery, and the low availability of a suitable autologous material [8,9]. The insufficient osteogenic ability, low osteoinductive property, and inadequate bone regeneration potential of synthetic bone grafting materials and xenografts reduce their capability in enhancing bone healing in large bone defects [1,10,13]. A combination of synthetic and xenograft bone grafting materials (Smartbone® ) has been proposed and developed

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Discussion

Conclusion