Chen Charlotte H, Hsu Erin L, Stupp Samuel I
Simpson Querrey Institute, Northwestern University, 303 East Superior Street, Chicago, IL 60611, USA; Department of Materials Science and Engineering, Northwestern University, 2220 Campus Drive, Evanston, IL 60208, USA.
Simpson Querrey Institute, Northwestern University, 303 East Superior Street, Chicago, IL 60611, USA; Department of Orthopaedic Surgery, Northwestern University, 676 North St. Clair Street, Chicago, IL 60611, USA.
Bone. 2020 Dec;141:115565. doi: 10.1016/j.bone.2020.115565. Epub 2020 Jul 31.
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 orthopaedic surgery to maximize their utility for clinical translation.
重组人骨形态发生蛋白（BMPs）在促进骨愈合方面已取得临床成功，但它们也伴有不良副作用。开发能够将BMP保留在缺损部位并使其疗效最大化的改良BMP载体，将降低治疗性BMP剂量，从而改善其安全性。在本综述中，我们讨论了使用自组装肽（一类合成超分子生物材料）来递送重组BMP的优势。肽两亲分子（PAs）是一类广泛的自组装肽，在过去十年中，人们对PAs用于BMP递送和骨再生进行了广泛探索。与许多自组装肽系统一样，PAs可以设计成形成纳米纤维超分子生物材料，其中分子通过非共价键结合在一起。通过将化学部分或生物表位与PA分子偶联，可以将化学和生物学功能添加到PA纳米纤维中。例如，PA纳米纤维已被设计成结合硫酸乙酰肝素，硫酸乙酰肝素是一种已知能结合BMP并增强其信号的天然多糖。或者，PA纳米纤维已被设计成合成模拟硫酸乙酰肝素的结构和功能，或直接特异性结合BMP。在小动物模型中，这些受生物启发的PA材料已显示出使用比既定治疗剂量低10至100倍的BMP促进骨再生的能力。这些有前景的结果促使人们在大型动物模型中对PAs进行进一步评估，在临床转化之前必须确定它们的安全性和有效性。我们最后讨论了将PAs与骨科手术中使用的其他材料结合以最大化其临床转化效用的可能性。
