Hierarchical Nanofibrous Microspheres with Controlled Growth Factor Delivery for Bone Regeneration.
Hierarchical Nanofibrous Microspheres with Controlled Growth Factor Delivery for Bone Regeneration.
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DOI：
10.1002/adhm.201500531
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发表时间：
2015-12-09
影响因子：
10
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Ma C;Jing Y;Sun H;Liu X
将可控生长因子递送和仿生结构整合到微球中是开发用于组织工程的新型可注射生物材料的具有挑战性但有吸引力的策略。在这项工作中，我们开发了一种独特的分层纳米球封装在微球支架系统的骨组织再生。首先，我们合成了肝素结合的明胶（HG），提供骨形态发生蛋白2（BMP 2）的结合域，以稳定这种生长因子，保护它免受变性和蛋白水解降解，并随后延长其持续释放。接下来，我们开发了一种独特的方法，包括油包油包水（W/O/O）双乳液过程和热诱导相分离，以将BMP 2结合的HG纳米球包封到纳米纤维微球中。该纳米纤维微球由合成纳米纤维自组装而成，具有上级表面积、高孔隙率、低密度，是支持细胞粘附和组织向内生长的优良载体。BMP 2在分级微球中以多重控制的方式释放（通过与肝素的结合以及纳米球和微球的包封）并保持其高生物活性。体内颅骨缺损模型证实，这种独特的分层微球是一种优良的骨诱导支架，用于增强骨再生。通过选择不同的生长因子，这种分级微球系统可以很容易地应用于其他类型的组织再生。我们的工作扩大了为先进的再生疗法开发新的可注射生物材料的能力。
The integration of controlled growth factor delivery and biomimetic architecture into a microsphere is a challenging but attractive strategy for developing new injectable biomaterials for tissue engineering. In this work, we developed a unique hierarchical nanosphere-encapsulated-in-microsphere scaffolding system for bone tissue regeneration. First, we synthesized heparin-conjugated gelatin (HG) that provides binding domains for bone morphogenetic protein 2 (BMP2) to stabilize this growth factor, protect it from denaturation and proteolytic degradation, and subsequently prolong its sustained release. Next, we developed a unique approach that includes a water-in-oil-in-oil (W/O/O) double emulsion process and a thermally induced phase separation to encapsulate BMP2-binding HG nanospheres into nanofibrous microspheres. The nanofibrous microsphere was self-assembled from synthetic nanofibers, and had superior surface area, high porosity, low density, and was an excellent carrier to support cell adhesion and tissue in-growth. BMP2 in the hierarchical microsphere was released in a multiple-controlled manner (by the binding with heparin and encapsulation of the nanosphere and microsphere) and retained its high bioactivity. An in vivo calvarial defect model confirmed that this unique hierarchical microsphere was an excellent osteoinductive scaffold for enhanced bone regeneration. By choosing different growth factors, this hierarchical microsphere system can be easily applied to other types of tissue regeneration. Our work expands the ability to develop new injectable biomaterials for advanced regenerative therapies.