Prolonged delivery of BMP-2 by a non-polymer hydrogel for bone defect regeneration
Prolonged delivery of BMP-2 by a non-polymer hydrogel for bone defect regeneration
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通过非聚合物水凝胶长期递送骨形态发生蛋白 - 2用于骨缺损再生
DOI：
10.1007/s13346-017-0451-y
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发表时间：
2018-02-01
影响因子：
5.4
通讯作者：
Chassande, Olivier
中科院分区：
文献类型：
--
作者：
Maisani, Mathieu;Sindhu, K. R.;Chassande, Olivier
骨形态发生蛋白2（BMP-2）是一种有效的骨形成诱导剂，目前用于有限数量的临床适应症，以治疗广泛的骨丢失。扩展该分子的应用领域需要设计递送系统以保护蛋白质免于早期降解并允许缓慢的长期释放。本研究描述了使用非聚合物水凝胶，基于小的两亲性糖基-核脂质到胶束结构中的自组装，作为BMP-2的新型递送系统。BMP-2很容易封装在糖基-核苷基-氟化（GNF）为基础的凝胶和缓慢释放在体外，同时保持其成骨活性。当将含有荧光团标记的BMP-2的水凝胶片沉积到小鼠的颅骨缺损上时，在活小鼠中检测到的信号逐渐降低，并且在3周时仍然可以检测到。凝胶包埋蛋白在术后8周促进了颅骨缺损的显著再生。相反，当将不含水凝胶的BMP-2溶液注射到缺损中时，荧光信号迅速下降，并且没有观察到显著的骨形成。在异位骨形成的皮下模型中揭示了基于GNF的水凝胶作为低剂量BMP-2的可注射递送系统的独特性质。注射BMP-2负载的GNF水凝胶块引起松质骨的形成，显示出包含骨髓的重塑骨的所有典型特征。这些结果表明，这种基于GNF的水凝胶是一种易于使用的、有效的BMP-2和成骨材料递送系统，以支持骨再生。
Bone morphogenetic protein 2 (BMP-2) is a potent inducer of bone formation that is currently used in a limited number of clinical indications to treat extensive bone loss. Extending the field of applications of this molecule requires design of the delivery system to protect the protein from early degradation and allow a slow long-term release. This study describes the use of a non-polymer hydrogel, based on the self-assembly of small amphiphilic glycosyl-nucleolipids into micellar structures, as a new type of delivery system for BMP-2. BMP-2 was readily encapsulated in glycosyl-nucleosyl-fluorinated (GNF)-based gels and slowly released in vitro, while maintaining its osteogenic activity. When hydrogel pieces containing fluorophore-tagged BMP-2 were deposited onto a calvaria defect in mouse, the signal detected in living mice gradually decreased and was still detectable at 3 weeks. Gel-embedded protein promoted significant calvarial bone defect regeneration at 8 weeks after surgery. In contrast, when a solution of BMP-2 without hydrogel was injected into the defects, the fluorescence signal decreased rapidly and no significant bone formation was observed. The unique property of the GNF-based hydrogel as an injectable delivery system for low doses of BMP-2 was revealed in a subcutaneous model of ectopic bone formation. Injected BMP-2-laden GNF hydrogel blocks elicited the formation of cancellous bone, showing all the typical features of remodeling bone that contains bone marrow. These results show that this GNF-based hydrogel is an easy-to-use, efficient delivery system for BMP-2 and osteogenic material to support bone regeneration.