分會(huì)

第六十分會(huì)：仿生材料化學(xué)

摘要

細(xì)胞外基質(zhì)(ECM)是人體重要的三維纖維網(wǎng)絡(luò)，具有多級(jí)自組裝結(jié)構(gòu)和多樣的生理功能，在維持細(xì)胞和組織的結(jié)構(gòu)和生理功能中發(fā)揮主導(dǎo)作用。因此，ECM仿生材料的構(gòu)建一直是組織工程和再生醫(yī)學(xué)領(lǐng)域的研究熱點(diǎn)。膠原蛋白、彈性蛋白等纖維蛋白是ECM的主要組成部分，能夠自組裝形成纖維網(wǎng)絡(luò)，被廣泛用于仿生ECM的結(jié)構(gòu)和功能。但是，上述蛋白主要來自動(dòng)物組織提取，存在病毒傳播隱患、免疫原性和批次間差異大等嚴(yán)重問題。自組裝多肽具有質(zhì)量可控、易于修飾和無病毒傳播風(fēng)險(xiǎn)等優(yōu)點(diǎn)，在ECM的仿生領(lǐng)域逐漸引起關(guān)注。然而，現(xiàn)有自組裝多肽大多基于非共價(jià)相互作用，形成的組裝材料極易受到外界環(huán)境的影響，極大地限制其臨床應(yīng)用。受天然ECM的啟發(fā)，我們首次構(gòu)建了一系列富含酪氨酸(Tyr)的共價(jià)自組裝三嵌段膠原多肽。該三嵌段多肽包括中間含有Tyr的三螺旋結(jié)構(gòu)域和完全由Tyr組成的N端和C端結(jié)構(gòu)域。在[Ru(II)byp3]2+的催化作用下，該體系多肽能夠以頭尾相接和肩并肩的形式，共價(jià)自組裝形成膠原蛋白仿生支架。相較于非共價(jià)作用介導(dǎo)的組裝材料，該共價(jià)自組裝支架對(duì)外界環(huán)境不敏感，可以在多種pH和離子強(qiáng)度下穩(wěn)定存在。中間三螺旋結(jié)構(gòu)域中可以引入多種功能序列，如整合素結(jié)合序列GFOGER，而不影響組裝材料的結(jié)構(gòu)，同時(shí)賦予其功能。我們?cè)O(shè)計(jì)的富含Tyr的共價(jià)自組裝三嵌段多肽，提供了一種廣泛適用的超穩(wěn)定的多肽基仿生材料的構(gòu)建策略，能夠成功仿生ECM的結(jié)構(gòu)和功能，在組織工程和再生醫(yī)學(xué)領(lǐng)域具有廣闊的應(yīng)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.

關(guān)鍵詞

細(xì)胞外基質(zhì);膠原蛋白仿生材料;膠原多肽;共價(jià)自組裝;酪氨酸

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