Enhanced osseous integration of human trabecular allografts following surface modification with bioactive lipids.

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.

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，将鞘脂生长因子FTY720递送至胫骨骨折和临界大小颅骨缺损的啮齿动物模型中。我们表明，从可注射的ECM凝胶中释放的FTY720可能会加速小鼠胫骨骨折模型中的骨痂形成、消退以及骨量增加。接着我们发现FTY720直接与人小梁同种异体骨结合，并在体外1周多的时间内释放。用FTY720涂层移植物治疗的大鼠临界大小颅骨缺损显示血管生成和骨沉积增加，组织学和微型计算机断层扫描（microCT）证据表明移植物内和缺损空隙处的骨形成增强。免疫组织化学分析表明，FTY720涂层移植物内的成骨作用与CD68⁺巨噬细胞浸润减少以及CD29⁺骨祖细胞募集有关。因此，FTY720与基质的结合代表了一种有前景且稳健的骨再生策略，具有潜在的临床转化性。