分会

第六十分会：仿生材料化学

摘要

细胞外基质(ECM)是人体重要的三维纤维网络，具有多级自组装结构和多样的生理功能，在维持细胞和组织的结构和生理功能中发挥主导作用。因此，ECM仿生材料的构建一直是组织工程和再生医学领域的研究热点。胶原蛋白、弹性蛋白等纤维蛋白是ECM的主要组成部分，能够自组装形成纤维网络，被广泛用于仿生ECM的结构和功能。但是，上述蛋白主要来自动物组织提取，存在病毒传播隐患、免疫原性和批次间差异大等严重问题。自组装多肽具有质量可控、易于修饰和无病毒传播风险等优点，在ECM的仿生领域逐渐引起关注。然而，现有自组装多肽大多基于非共价相互作用，形成的组装材料极易受到外界环境的影响，极大地限制其临床应用。受天然ECM的启发，我们首次构建了一系列富含酪氨酸(Tyr)的共价自组装三嵌段胶原多肽。该三嵌段多肽包括中间含有Tyr的三螺旋结构域和完全由Tyr组成的N端和C端结构域。在[Ru(II)byp3]2+的催化作用下，该体系多肽能够以头尾相接和肩并肩的形式，共价自组装形成胶原蛋白仿生支架。相较于非共价作用介导的组装材料，该共价自组装支架对外界环境不敏感，可以在多种pH和离子强度下稳定存在。中间三螺旋结构域中可以引入多种功能序列，如整合素结合序列GFOGER，而不影响组装材料的结构，同时赋予其功能。我们设计的富含Tyr的共价自组装三嵌段多肽，提供了一种广泛适用的超稳定的多肽基仿生材料的构建策略，能够成功仿生ECM的结构和功能，在组织工程和再生医学领域具有广阔的应用前景。 Extracellular matrix (ECM) serves as a vital three-dimensional scaffold for tissues and organs throughout the human body, playing a dominant role in their structural integrity and physiological function. Due to their hierarchical structure and biofunction, the construction of ECM mimetic biomaterials has received tremendous attention in tissue engineering and regenerative medicine. As the major components of the ECM, fibrous proteins such as collagen and elastin have been employed to mimic the structure and function of ECM. However, proteins of animal sources suffer from severe disadvantages such as pathogen transmission, immunogenicity and batch-to-batch variability. The construction of self-assembled peptides to mimic ECM has been a hot target due to their advantages of easy synthesis, convenient quality control and no virus transmission. A variety of non-covalent strategies have been developed to trigger the self-assembly of ECM-derived peptides; however, their high susceptibility to external environment poses an insurmountable challenge in biomedical applications. Inspired by native ECM, we have for the first time discovered a novel series of covalent self-assembled tyrosine-rich triblock peptides consisting of a central tyrosine-containing triple helical block and two tyrosine-rich blocks at both the N-/C-terminals. The triblock peptides have been demonstrated to self-assemble into exquisite three-dimensional collagen mimetic scaffolds by ruthenium-mediated head-to-tail and shoulder-to-shoulder assembly of tyrosines. In contrast to non-covalent assembled peptides, the covalent assembled triblock peptides form highly stable scaffolds which are insusceptible to various ionic strength and broad pH conditions. Integrin-binding motif GFOGER has been demonstrated as a vivid example of convenient incorporation of functional sequences into the tyrosine-rich triblock peptides without affecting their assembly. The covalent self-assembly of tyrosine-rich triblock peptides provides a versatile approach to create highly stable peptide-based biomaterials that can mimic the structure and function of ECM, which has great potential in tissue engineering and regenerative medicine.

关键词

细胞外基质;胶原蛋白仿生材料;胶原多肽;共价自组装;酪氨酸

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