Enhanced osseous integration of human trabecular allografts following surface modification with bioactive lipids.
Enhanced osseous integration of human trabecular allografts following surface modification with bioactive lipids.
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DOI：
10.1007/s13346-015-0244-0
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发表时间：
2016-04
影响因子：
5.4
通讯作者：
Botchwey E
中科院分区：
文献类型：
--
作者：
Wang T;Krieger J;Huang C;Das A;Francis MP;Ogle R;Botchwey E
在这项研究中，我们使用细胞外基质(ECM)凝胶和人同种异体骨作为基质载体，将鞘磷脂生长因子FTY720转移到啮齿动物的胫骨骨折和临界大小的颅骨缺损模型中。我们发现从可注射的ECM凝胶中释放的FTY720可以加速小鼠胫骨骨折模型中骨痂的形成和溶解以及骨体积。然后，我们发现FTY720直接结合到人的同种异体骨小梁上，并在体外释放超过1周。FTY720涂层移植物处理的大鼠临界大小的颅骨缺损显示血管形成和骨沉积增加，组织学和微计算机断层扫描(MicroCT)证据表明，移植物内骨形成增强，缺损区空洞。免疫组织化学分析表明，FTY720涂层移植物的成骨与CD68+巨噬细胞浸润减少和CD29+骨祖细胞募集有关。因此，FTY720的基质结合代表了一种有前景的、具有潜在临床可译性的强健的骨再生策略。
In this study, we used extracellular matrix (ECM) gels and human bone allograft as matrix vehicles to deliver the sphingolipid growth factor FTY720 to rodent models of tibial fracture and a critical-sized cranial defect. We show that FTY720 released from injectable ECM gels may accelerate callous formation and resolution and bone volume in a mouse tibial fracture model. We then show that FTY720 binds directly to human trabecular allograft bone and releases over 1 week in vitro. Rat critical-sized cranial defects treated with FTY720-coated grafts show increases in vascularization and bone deposition, with histological and micro-computed topography (microCT) evidence of enhanced bone formation within the graft and defect void. Immunohistochemical analysis suggests that osteogenesis within FTY720-coated grafts is associated with reduced CD68+ macrophage infiltration and recruitment of CD29+ bone progenitor cells. Matrix binding of FTY720 thus represents a promising and robust bone regeneration strategy with potential clinical translatability.