Guangdong Provincial Key Laboratory of Spine and Spinal Cord Reconstruction, The Fifth Affiliated Hospital (Heyuan Shenhe People's Hospital), Jinan University, Heyuan 517000, China; Department of Materials Science and Engineering, Engineering Research Center of Artificial Organs and Materials, Jinan University, Guangzhou 510632, China.
Department of Materials Science and Engineering, Engineering Research Center of Artificial Organs and Materials, Jinan University, Guangzhou 510632, China.
Int J Biol Macromol. 2024 Aug;274(Pt 1):132970. doi: 10.1016/j.ijbiomac.2024.132970. Epub 2024 Jun 12.
Bone defects can interfere with bone healing by disrupting the local environment, resulting in vascular damage and hypoxia. Under these conditions, insufficient oxygen availability is a significant factor that exacerbates disease by blocking angiogenesis or osteogenesis. Exosomes play a crucial role in intercellular communication and modulation of inflammation to aid bone regeneration. However, the distance between exosomes and areas of damage can hinder efficient bone generation and cell survival. To overcome this limitation, we fabricated a continuous oxygen-supplying composite scaffold, with the encapsulation of calcium peroxide in a polylactic acid three-dimensional (3D) printing construct (CPS), as both an oxygen source and hydroxyapatite (HAP) precursor. Furthermore, bone marrow mesenchymal stem cell (BMSC)-derived exosomes were incorporated into hyaluronic acid (HA) hydrogels to stimulate cell growth and modulate inflammation. The release of exosomes into cells leads to an increase in alkaline phosphatase production. In vivo results demonstrated that the composite scaffold regulated the inflammatory microenvironment, relieved tissue hypoxia, and promoted new bone formation. These results indicate that the synergistic effect of exosomes and oxygen promoted the proliferation of BMSCs, alleviated inflammation and exhibited excellent osteogenic properties. In conclusion, this osteogenic functional composite scaffold material offers a highly effective approach for bone repair.
骨缺损可通过破坏局部环境干扰骨愈合，导致血管损伤和缺氧。在这些条件下，氧气供应不足是通过阻断血管生成或成骨作用使疾病恶化的一个重要因素。外泌体在细胞间通讯和炎症调节中发挥着关键作用，有助于骨再生。然而，外泌体与损伤区域之间的距离可能会阻碍有效的骨生成和细胞存活。为了克服这一限制，我们制备了一种连续供氧的复合支架，将过氧化钙封装在聚乳酸三维（3D）打印结构（CPS）中，作为氧源和羟基磷灰石（HAP）前体。此外，将骨髓间充质干细胞（BMSC）衍生的外泌体掺入透明质酸（HA）水凝胶中，以刺激细胞生长和调节炎症。外泌体向细胞内的释放会导致碱性磷酸酶产量增加。体内结果表明，该复合支架调节炎症微环境，缓解组织缺氧，并促进新骨形成。这些结果表明，外泌体和氧气的协同作用促进了 BMSCs 的增殖，减轻了炎症，并表现出优异的成骨特性。总之，这种成骨功能复合支架材料为骨修复提供了一种高效的方法。
