Department of Oral Biology, The State University of New York at Buffalo, Buffalo, New York 14214, USA.
Tissue Eng Part A. 2013 Feb;19(3-4):508-18. doi: 10.1089/ten.tea.2012.0244. Epub 2012 Nov 16.
The repair of craniofacial bone defects is surgically challenging due to the complex anatomical structure of the craniofacial skeleton. Current strategies for bone tissue engineering using a preformed scaffold have not resulted in the expected clinical regeneration due to difficulty in seeding cells into the deep internal space of scaffold, and the inability to inject them in minimally invasive surgeries. In this study, we used the osteoconductive and mechanical properties of nano-scale calcium sulfate (nCS) and the biocompatibility of alginate to develop the injectable nCS/alginate (nCS/A) paste, and characterized the effect of this nCS/A paste loaded with bone morphogenetic protein 2 (BMP2) gene-modified rat mesenchymal stem cells (MSCs) on bone and blood vessel growth. Our results showed that the nCS/A paste was injectable under small injection forces. The mechanical properties of the nCS/A paste were increased with an increased proportion of alginate. MSCs maintained their viability after the injection, and MSCs and BMP2 gene-modified MSCs in the injectable pastes remained viable, osteodifferentiated, and yielded high alkaline phosphatase activity. By testing the ability of this injectable paste and BMP2-gene-modified MSCs for the repair of critical-sized calvarial bone defects in a rat model, we found that BMP2-gene-modified MSCs in nCS/A (nCS/A+M/B2) showed robust osteogenic activity, which resulted in consistent bone bridging of the bone defects. The vessel density in nCS/A+M/B2 was significantly higher than that in the groups of blank control, nCS/A alone, and nCS/A mixed with MSCs (nCS/A+M). These results indicate that BMP2 promotes MSCs-mediated bone formation and vascularization in nCS/A paste. Overall, the results demonstrated that the combination of injectable nCS/A paste and BMP2-gene-modified MSCs is a new and effective strategy for the repair of bone defects.
颅颌面骨缺损的修复具有挑战性，因为颅颌面骨骼的解剖结构复杂。目前，使用预制支架进行骨组织工程的策略由于难以将细胞播种到支架的深部内部空间以及无法在微创手术中注射支架，因此并未达到预期的临床再生效果。在这项研究中，我们利用纳米硫酸钙（nCS）的骨传导性和机械性能以及藻酸盐的生物相容性，开发了可注射的 nCS/藻酸盐（nCS/A）糊剂，并研究了这种负载骨形态发生蛋白 2（BMP2）基因修饰大鼠间充质干细胞（MSCs）的 nCS/A 糊剂对骨和血管生长的影响。我们的结果表明，nCS/A 糊剂可以在较小的注射力下进行注射。nCS/A 糊剂的机械性能随着藻酸盐比例的增加而增加。MSCs 在注射后保持活力，并且可注射糊剂中的 MSCs 和 BMP2 基因修饰 MSCs 仍保持活力、成骨分化，并产生高碱性磷酸酶活性。通过测试这种可注射糊剂和 BMP2 基因修饰 MSCs 在大鼠模型中修复临界尺寸颅骨骨缺损的能力，我们发现 nCS/A 中的 BMP2 基因修饰 MSCs（nCS/A+M/B2）具有很强的成骨活性，导致骨缺损的骨桥接一致。nCS/A+M/B2 中的血管密度明显高于空白对照组、单独 nCS/A 组和 nCS/A 与 MSCs 混合组（nCS/A+M）。这些结果表明，BMP2 促进了 nCS/A 糊剂中 MSCs 介导的成骨和血管生成。总的来说，这些结果表明，可注射 nCS/A 糊剂和 BMP2 基因修饰 MSCs 的结合是修复骨缺损的一种新的有效策略。
