Supramolecular self-assembling peptides to deliver bone morphogenetic proteins for skeletal regeneration.
Supramolecular self-assembling peptides to deliver bone morphogenetic proteins for skeletal regeneration.
复制标题
超分子自组装肽，以递送骨形态发生蛋白以进行骨骼再生。
DOI：
10.1016/j.bone.2020.115565
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发表时间：
2020-12
期刊：
影响因子：
4.1
通讯作者：
Stupp SI
中科院分区：
文献类型：
--
作者：
Chen CH;Hsu EL;Stupp SI
重组人骨形态发生蛋白(BMPs)在促进骨愈合方面已显示出临床上的成功，但它们也与不良的副作用有关。改进的BMP载体的开发可以将BMP保留在缺损处并最大限度地发挥其疗效，这将减少治疗性BMP剂量，从而改善其安全性。在这篇综述中，我们讨论了利用自组装多肽这一类人工合成的超分子生物材料来运送重组骨形成蛋白的优点。多肽两亲性(Pas)是一类广泛的自组装多肽，在过去的十年中，Pas用于骨形态发生蛋白的传递和骨再生已经得到了广泛的探索。与许多自组装肽系统一样，PAS可以设计成纳米纤维超分子生物材料，其中分子通过非共价键连接在一起。通过将化学部分或生物表位偶联到PA分子上，可以将化学和生物功能添加到PA纳米纤维中。例如，PA纳米纤维被设计成与硫酸乙酰肝素结合，这是一种已知能结合骨形成蛋白并增强其信号的天然多糖。或者，PA纳米纤维被设计成合成模拟硫酸乙酰肝素的结构和功能，或者直接特异性地结合BMP。在小动物模型中，这些受生物启发的PA材料显示出使用BMP促进骨再生的能力，剂量比现有治疗剂量低10-100倍。这些有希望的结果推动了PAS在大型动物模型中的进一步评估，在临床转化之前，必须确定其安全性和有效性。最后，我们讨论了PAS与骨科手术中使用的其他材料相结合的可能性，以最大限度地发挥其在临床翻译中的作用。
Recombinant human bone morphogenetic proteins (BMPs) have shown clinical success in promoting bone healing, but they are also associated with unwanted side effects. The development of improved BMP carriers that can retain BMP at the defect site and maximize its efficacy would decrease the therapeutic BMP dose and thus improve its safety profile. In this review, we discuss the advantages of using self-assembling peptides, a class of synthetic supramolecular biomaterials, to deliver recombinant BMPs. Peptide amphiphiles (PAs) are a broad class of self-assembling peptides, and the use of PAs for BMP delivery and bone regeneration has been explored extensively over the past decade. Like many self-assembling peptide systems, PAs can be designed to form nanofibrous supramolecular biomaterials in which molecules are held together by non-covalent bonds. Chemical and biological functionality can be added to PA nanofibers, through conjugation of chemical moieties or biological epitopes to PA molecules. For example, PA nanofibers have been designed to bind heparan sulfate, a natural polysaccharide that is known to bind BMPs and potentiate their signal. Alternatively, PA nanofibers have been designed to synthetically mimic the structure and function of heparan sulfate, or to directly bind BMP specifically. In small animal models, these bio-inspired PA materials have shown the capacity to promote bone regeneration using BMP at doses 10 – 100 times lower than established therapeutic doses. These promising results have motivated further evaluation of PAs in large animal models, where their safety and efficacy must be established before clinical translation. We conclude with a discussion on the possiblity of combining PAs with other materials used in orthopedic surgery to maximize their utility for clinical translation.
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