Department of Rehabilitation, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Cardiac Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
J Biomed Mater Res A. 2019 Oct;107(10):2282-2295. doi: 10.1002/jbm.a.36737. Epub 2019 Jun 17.
Stem cell-based therapies provide a promising approach for bone repair. In the present work, we developed a novel 3D vehicle system for dual-delivery of encapsulated bone marrow mesenchymal stem cells (BM-MSCs) and bone morphogenetic protein-2 (BMP-2) for treatment of large bone defects. The vehicle system consists of sodium alginate microcapsules and polylactic acid (PLLA) microspheres. BM-MSCs are encapsulated in the microcapsules, and BMP-2 proteins are encapsulated in the PLLA microspheres. This vehicle system acted as a multicore structure for sustained release of BMP-2, which enabled pulsed dosing induction of osteogenic differentiation of the co-embedded BM-MSCs. in vitro experiments showed that the loaded BMP-2 was constitutively released up to 30 days. Bioactivity of the incorporated BMP-2 in the microspheres was preserved and osteogenic differentiation of the BM-MSCs in the microcapsules was improved. In vivo, osteogenesis studies demonstrated that satisfactory degree of repair of a rat calvarial defect was achieved with the delivery of either encapsulated BM-MSCs alone or encapsulated BMP-2 alone. Transplantation of encapsulated both BM-MSCs and BMP-2 exhibited the greatest repair potential following 4- or 8-weeks treatment. In conclusion, microencapsulation of BM-MSCs and BMP-2 promoted the maturity of newly generated bone and improved new bone formation. Transplantation of BM-MSCs and BMP-2 in our novel 3-D vehicle system is a promising strategy for regenerative therapies of large bone defects.
基于干细胞的治疗为骨修复提供了一种有前途的方法。在本工作中，我们开发了一种新型的 3D 载体系统，用于封装骨髓间充质干细胞（BM-MSCs）和骨形态发生蛋白-2（BMP-2）的双重递送，用于治疗大的骨缺损。该载体系统由海藻酸钠微胶囊和聚乳酸（PLLA）微球组成。BM-MSCs 被包封在微胶囊中，BMP-2 蛋白被包封在 PLLA 微球中。该载体系统作为 BMP-2 的缓释多芯结构，能够脉冲给药诱导共嵌入的 BM-MSCs 成骨分化。体外实验表明，负载的 BMP-2 持续释放长达 30 天。微球中掺入的 BMP-2 的生物活性得以保留，微胶囊中 BM-MSCs 的成骨分化得到改善。体内成骨研究表明，单独递送包封的 BM-MSCs 或包封的 BMP-2 可实现大鼠颅骨缺损的满意修复程度。4 或 8 周治疗后，同时递送包封的 BM-MSCs 和 BMP-2 表现出最大的修复潜力。总之，BM-MSCs 和 BMP-2 的微囊化促进了新生成骨的成熟，并改善了新骨形成。在我们的新型 3D 载体系统中移植 BM-MSCs 和 BMP-2 是大骨缺损再生治疗的一种有前途的策略。
