Institute of Stomatology, Chinese PLA General Hospital, Beijing 100853, China; Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an 710032, Shanxi, China.
Biomaterials. 2013 Dec;34(38):9998-10006. doi: 10.1016/j.biomaterials.2013.09.040. Epub 2013 Sep 27.
Reconstruction of large area bone defect with mechanical integrity to the skeleton is important for patient's rehabilitation. However with the limitation of scaffold material and suitable seed cell sources, the best treating strategy remains to be identified though various tissue engineering methods were reported. In this study, we investigated the feasibility of applying calcined bovine bone (CBB) which was coated by allograft bone marrow mesenchymal stem cells (BMSC)-sheet as a 3D scaffold material in bone repairing tissue engineering. The new scaffold material was implanted into osteoporosis rat cranial bone defects and repairing critical size bone defects (8 mm diameter). Data showed that CBB-BMSC-sheet combination had a stronger potential in osteogenic differentiation and mineralized formation both in vitro and in vivo than CBB-BMSC combination. In in vitro study BMSC-sheet had a more feasible characteristic upon bone repairing including richer ECM, larger mineralized area and stronger ALP activity in addition with a significant higher mRNA expression of osteogenic maker such as BMP-2, b-FGF, Col 1a1, OSX and Runx-2 than the control group. In in vivo study 3D reconstruction of micro CT, HE staining and bone strength results showed that newly formed bone in CBB-BMSC-sheet group was significant higher than that in CBB-BMSC group at 4, 8 and 12 weeks after transplantation in the aspect of area and volume. What was more, results indicated that allograft BMSC-sheet had survivaled in the scaffold material and participated in the newly formed bone which had the same thickness with surrounding autologous bone tissues after transplantation. Results of our study demonstrated that CBB-BMSC-sheet combination was a promising strategy in healing of large area bone defect in osteoporosis.
重建具有骨骼机械完整性的大面积骨缺损对于患者的康复至关重要。然而，由于支架材料和合适的种子细胞来源的限制，尽管已经报道了各种组织工程方法，但最佳治疗策略仍有待确定。在这项研究中，我们研究了将煅烧牛骨（CBB）与同种异体骨髓间充质干细胞（BMSC）片涂层作为 3D 支架材料应用于骨修复组织工程的可行性。将新型支架材料植入骨质疏松症大鼠颅骨缺损和修复临界尺寸骨缺损（8 毫米直径）。结果表明，CBB-BMSC 片组合在体外和体内的成骨分化和矿化形成方面比 CBB-BMSC 组合具有更强的潜力。在体外研究中，BMSC 片在骨修复方面具有更可行的特性，包括更丰富的细胞外基质、更大的矿化面积和更强的碱性磷酸酶活性，此外，成骨标志物如 BMP-2、b-FGF、Col 1a1、OSX 和 Runx-2 的 mRNA 表达也显著高于对照组。在体内研究中，3D 重建的微 CT、HE 染色和骨强度结果表明，在移植后 4、8 和 12 周，CBB-BMSC 片组新形成的骨在面积和体积方面均显著高于 CBB-BMSC 组。更重要的是，结果表明，同种异体 BMSC 片在支架材料中存活并参与了新形成的骨，其在移植后与周围自体骨组织具有相同的厚度。我们的研究结果表明，CBB-BMSC 片组合是治疗骨质疏松症大面积骨缺损的一种有前途的策略。
