Biomaterials Research Center, Biomedical Research Division, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea.
Department of Materials Science and Engineering, Seoul National University, Seoul, 08826, Republic of Korea.
Small. 2022 Jun;18(24):e2200416. doi: 10.1002/smll.202200416. Epub 2022 May 10.
Prompt and robust bone regeneration has been clinically achieved using supraphysiological doses of bone morphogenetic protein-2 (BMP-2) to overcome the short half-life and rapid clearance. However, uncontrolled burst release of exogenous BMP-2 causes severe complications such as heterotopic ossification and soft tissue inflammation. Therefore, numerous researches have focused on developing a new BMP-2 delivery system for a sustained release profile by immobilizing BMP-2 in various polymeric vehicles. Herein, to avoid denaturation of BMP-2 and enhance therapeutic action via localized delivery, a complex coacervate consisting of fucoidan, a marine-derived glycosaminoglycan, and poly-l-lysine (PLL) is fabricated. Superior BMP-2 binding ability and electrostatic interaction-driven engulfment enable facile and highly efficient microencapsulation of BMP-2. The microencapsulation ability of the coacervate significantly improves BMP-2 bioactivity and provides protection against antagonist and proteolysis, while allowing prolonged release. Moreover, BMP-2 containing coacervate is coated on conventional collagen sponges. The bioactivity and localized bone regenerating ability are confirmed through in vitro (human-derived stem cells), and in vivo (calvarial bone defect model) evaluations.
使用超生理剂量的骨形态发生蛋白-2（BMP-2）来克服半衰期短和快速清除的问题，临床上已经实现了快速而稳健的骨再生。然而，外源性 BMP-2 的不受控制的爆发式释放会导致严重的并发症，如异位骨化和软组织炎症。因此，许多研究都集中在开发新的 BMP-2 递送系统，通过将 BMP-2固定在各种聚合物载体中实现持续释放。在此，为了避免 BMP-2 的变性并通过局部递送增强治疗作用，制备了一种由海洋来源的糖胺聚糖褐藻糖胶和聚-L-赖氨酸（PLL）组成的复杂凝聚体。优异的 BMP-2 结合能力和静电相互作用驱动的吞噬作用使得 BMP-2 的微封装既简单又高效。凝聚体的微封装能力显著提高了 BMP-2 的生物活性，并提供了对抗拮抗剂和蛋白水解的保护，同时允许其持续释放。此外，含有 BMP-2 的凝聚体被涂覆在常规的胶原海绵上。通过体外（人源干细胞）和体内（颅顶骨缺损模型）评估证实了其生物活性和局部骨再生能力。
