Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès (Barcelona), Spain.
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès (Barcelona), Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Instituto de Salud Carlos III, 08193 Cerdanyola del Vallès (Barcelona), Spain.
Biotechnol Adv. 2022 Dec;61:108032. doi: 10.1016/j.biotechadv.2022.108032. Epub 2022 Sep 9.
Fundamental clinical areas such as drug delivery and regenerative medicine require biocompatible materials as mechanically stable scaffolds or as nanoscale drug carriers. Among the wide set of emerging biomaterials, polypeptides offer enticing properties over alternative polymers, including full biocompatibility, biodegradability, precise interactivity, structural stability and conformational and functional versatility, all of them tunable by conventional protein engineering. However, proteins from non-human sources elicit immunotoxicities that might bottleneck further development and narrow their clinical applicability. In this context, selecting human proteins or developing humanized protein versions as building blocks is a strict demand to design non-immunogenic protein materials. We review here the expanding catalogue of human or humanized proteins tailored to execute different levels of scaffolding functions and how they can be engineered as self-assembling materials in form of oligomers, polymers or complex networks. In particular, we emphasize those that are under clinical development, revising their fields of applicability and how they have been adapted to offer, apart from mere mechanical support, highly refined functions and precise molecular interactions.
基础临床领域，如药物输送和再生医学，需要生物相容性材料作为机械稳定的支架或纳米级药物载体。在新兴的生物材料中，多肽在某些方面优于其他聚合物，包括完全的生物相容性、可生物降解性、精确的交互性、结构稳定性以及构象和功能的多功能性，所有这些都可以通过传统的蛋白质工程进行调节。然而，非人类来源的蛋白质会引起免疫毒性，这可能会限制进一步的发展，并缩小其临床应用范围。在这种情况下，选择人类蛋白质或开发人源化蛋白质版本作为构建块是设计非免疫原性蛋白质材料的严格要求。我们在这里回顾了为执行不同层次的支架功能而专门设计的不断扩大的人类或人源化蛋白质目录，以及它们如何被工程化为具有自组装功能的低聚物、聚合物或复杂网络形式的材料。特别是，我们强调了那些正在进行临床开发的蛋白质，回顾了它们的应用领域以及如何对其进行改造，以提供除了单纯的机械支撑之外的更精细的功能和精确的分子相互作用。
