Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Nanoscale. 2017 May 25;9(20):6765-6776. doi: 10.1039/c7nr00601b.
Poor bone formation remains a key risk factor associated with acellular scaffolds that occurs in some bone defects, particularly in patients with metabolic bone disorders and local osteoporosis. We herein fabricated for the first time layered double hydroxide-chitosan porous scaffolds loaded with PFTα (LDH-CS-PFTα scaffolds) as therapeutic bone scaffolds for the controlled release of PFTα to enhance stem cell osteogenic differentiation and bone regeneration. The LDH-CS scaffolds had three-dimensional interconnected macropores, and plate-like LDH nanoparticles were uniformly dispersed within or on the CS films. The LDH-CS scaffolds exhibited appropriate PFTα drug delivery due to hydrogen bonding among LDH, CS and PFTα. In vitro functional studies demonstrated that the PFTα molecules exhibited potent ability to induce osteogenesis of hBMSCs via the GSK3β/β-catenin pathway, and the LDH-CS-PFTα scaffolds significantly enhanced the osteogenic differentiation of hBMSCs. In vivo studies revealed significantly increased repair and regeneration of bone tissue in cranial defect model rats compared to control rats at 12 weeks post-implantation. In conclusion, the LDH-CS-PFTα scaffolds exhibited excellent osteogenic differentiation and bone regeneration capability and hold great potential for applications in defined local bone regeneration.
骨形成不良仍然是与脱细胞支架相关的一个关键风险因素，这种情况发生在一些骨缺损中，特别是在代谢性骨疾病和局部骨质疏松症患者中。本文首次制备了载有 PFTα 的层状双氢氧化物-壳聚糖多孔支架（LDH-CS-PFTα 支架）作为治疗性骨支架，以控制 PFTα 的释放，从而增强干细胞成骨分化和骨再生。LDH-CS 支架具有三维相互连接的大孔，并且板状 LDH 纳米颗粒均匀分散在 CS 膜内或 CS 膜上。由于 LDH、CS 和 PFTα 之间的氢键作用，LDH-CS 支架表现出适当的 PFTα 药物释放。体外功能研究表明，PFTα 分子通过 GSK3β/β-catenin 途径表现出诱导 hBMSCs 成骨的强大能力，并且 LDH-CS-PFTα 支架显著增强了 hBMSCs 的成骨分化。体内研究表明，与对照组大鼠相比，植入后 12 周时颅骨缺损模型大鼠的骨组织修复和再生明显增加。总之，LDH-CS-PFTα 支架表现出优异的成骨分化和骨再生能力，在特定部位的骨再生中有很大的应用潜力。
