Division of Advanced Prosthodontics, University of California at Los Angeles , 10833 Le Conte Avenue, Los Angeles, California 90095, United States.
Department of Bioengineering, University of California at Los Angeles , 420 Westwood Plaza, Los Angeles, California 90095, United States.
ACS Nano. 2017 Aug 22;11(8):8055-8063. doi: 10.1021/acsnano.7b02702. Epub 2017 Aug 11.
Sterosomes are recently developed types of non-phospholipid liposomes formed from single-chain amphiphiles and high content of sterols. Although sterosomes presented significantly increased stability compared to conventional phospholipid liposomes, current sterosome biomaterials are not truly bioactive and have no intrinsic therapeutic effects. The purpose of this study was to develop a sterosome formulation with osteoinductive properties by an effective selection of sterol, one of the sterosome components. Oxysterols are oxidized derivatives of cholesterol and are known to stimulate osteogenesis and bone formation. Thus, 20S-hydroxycholesterol (Oxy), one of the most potent oxysterols for bone regeneration, was examined as a promising candidate molecule to form fluid lamellar phases with a single-chain amphiphile, namely, stearylamine (SA). First, the optimal composition was identified by investigating the phase behavior of SA/Oxy mixtures. Next, the capacity of the optimized SA/Oxy sterosomes to promote osteogenic differentiation of bone marrow stromal cells was assessed in vitro in a hydrogel environment. Furthermore, we explored the effects of osteogenic oxysterol sterosomes in vivo with the mouse critical-sized calvarial defect model. Our results showed that SA/Oxy sterosomes induced osteogenic differentiation in vitro and enhanced calvarial healing without delivery of additional therapeutic agents, indicating their intrinsic bone-forming potential. This study suggests a promising non-phospholipid liposomal platform with osteoinductive properties for delivery of small molecular drugs and/or other therapeutic genes for enhanced bone formation.
甾休是由单链两亲分子和高含量固醇形成的新型非磷脂脂质体。尽管甾休与传统的磷脂脂质体相比表现出显著提高的稳定性，但目前的甾休生物材料不是真正的生物活性的，也没有内在的治疗效果。本研究的目的是通过有效选择甾休成分之一的固醇，开发具有成骨特性的甾休制剂。氧化固醇是胆固醇的氧化衍生物，已知可刺激成骨作用和骨形成。因此，20S-羟基胆固醇（Oxy）作为最有效的骨再生氧化固醇之一，被视为与单链两亲体，即硬脂胺（SA）形成流体层状相的有前途的候选分子进行了研究。首先，通过研究 SA/Oxy 混合物的相行为来确定最佳组成。接下来，在水凝胶环境中评估优化的 SA/Oxy 甾休对骨髓基质细胞成骨分化的体外促进能力。此外，我们还通过小鼠临界大小颅骨缺损模型探索了成骨氧化固醇甾休的体内作用。结果表明，SA/Oxy 甾休在体外诱导成骨分化，并增强颅骨愈合，而无需额外的治疗剂，表明其具有内在的成骨潜力。这项研究为递送小分子药物和/或其他治疗基因以增强骨形成提供了一种有前途的具有成骨特性的非磷脂脂质体平台。
