Department of Orthopaedics and Rehabilitation, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Tissue Eng Part A. 2010 Jul;16(7):2369-79. doi: 10.1089/ten.TEA.2009.0585.
Scaffolds prepared from biodegradable polyurethanes (PUR) have been investigated as a supportive matrix and delivery system for skin, cardiovascular, and bone tissue engineering. In this study, we combined reactive two-component PUR scaffolds with lovastatin (LV), which has been reported to have a bone anabolic effect especially when delivered locally, for effective bone tissue regeneration. To incorporate LV into PUR scaffolds, LV was combined with the hardener component before scaffold synthesis. The PUR scaffolds containing LV (PUR/LV) demonstrated a highly porous structure with interconnected pores, which supported in vitro cell attachment and proliferation and in vivo osteoconductive potential. The PUR/LV scaffolds showed sustained release of biologically active LV, as evidenced by the fact that LV releasates significantly enhanced osteogenic differentiation of osteoblastic cells in vitro. A study of bone formation in vivo using a rat plug defect model showed that the PUR/LV scaffolds were biocompatible. Further, locally delivered LV enhanced new bone formation in the PUR scaffolds at week 4, while there were no obvious effects at week 2. These results suggest that the sustained LV delivery system from PUR scaffolds is a potentially safe and effective device for bone regeneration.
用可生物降解的聚氨酯(PUR)制备的支架已被研究作为皮肤、心血管和骨组织工程的支持基质和输送系统。在这项研究中,我们将反应性双组分 PUR 支架与洛伐他汀(LV)结合,LV 已被报道具有骨合成代谢作用,特别是当局部给药时,可有效促进骨组织再生。为了将 LV 掺入 PUR 支架中,在支架合成前将 LV 与固化剂成分结合。含有 LV 的 PUR 支架(PUR/LV)表现出具有相互连接孔的高度多孔结构,这支持了体外细胞附着和增殖以及体内成骨潜力。事实证明,PUR/LV 支架中释放的 LV 具有生物活性,这表明 LV 释放物显著增强了体外成骨细胞的成骨分化。体内大鼠塞块缺损模型的骨形成研究表明,PUR/LV 支架具有生物相容性。此外,局部给予 LV 可增强第 4 周时 PUR 支架中的新骨形成,而第 2 周时则没有明显效果。这些结果表明,从 PUR 支架中持续释放 LV 的系统是一种潜在安全有效的骨再生装置。