关键词: immunotherapy injectable hydrogels polypeptides secondary conformation stimuli responsive tissue engineering

来  源:   DOI:10.1093/rb/rbad039   PDF(Pubmed)

Abstract:
Stimuli-responsive synthetic polypeptide-containing block copolymers have received considerable attention in recent years. Especially, unique thermo-induced sol-gel phase transitions were observed for elaborately-designed amphiphilic diblock copolypeptides and a range of poly(ethylene glycol) (PEG)-polypeptide block copolymers. The thermo-induced gelation mechanisms involve the evolution of secondary conformation, enhanced intramolecular interactions, as well as reduced hydration and increased chain entanglement of PEG blocks. The physical parameters, including polymer concentrations, sol-gel transition temperatures and storage moduli, were investigated. The polypeptide hydrogels exhibited good biocompatibility in vitro and in vivo, and displayed biodegradation periods ranging from 1 to 5 weeks. The unique thermo-induced sol-gel phase transitions offer the feasibility of minimal-invasive injection of the precursor aqueous solutions into body, followed by in situ hydrogel formation driven by physiological temperature. These advantages make polypeptide hydrogels interesting candidates for diverse biomedical applications, especially as injectable scaffolds for 3D cell culture and tissue regeneration as well as depots for local drug delivery. This review focuses on recent advances in the design and preparation of injectable, thermo-induced physically crosslinked polypeptide hydrogels. The influence of composition, secondary structure and chirality of polypeptide segments on the physical properties and biodegradation of the hydrogels are emphasized. Moreover, the studies on biomedical applications of the hydrogels are intensively discussed. Finally, the major challenges in the further development of polypeptide hydrogels for practical applications are proposed.
摘要:
近年来,含有刺激响应性合成多肽的嵌段共聚物受到了相当大的关注。尤其是,对于精心设计的两亲性二嵌段共多肽和一系列聚(乙二醇)(PEG)多肽嵌段共聚物,观察到了独特的热诱导的溶胶-凝胶相变。热诱导的凝胶化机制涉及次级构象的演变,增强分子内相互作用,以及减少的水合作用和增加的PEG嵌段的链缠结。物理参数,包括聚合物浓度,溶胶-凝胶转变温度和储能模量,被调查了。多肽水凝胶具有良好的体内外生物相容性,并显示生物降解周期为1至5周。独特的热诱导溶胶-凝胶相变提供了将前体水溶液微创注射到体内的可行性,随后由生理温度驱动的原位水凝胶形成。这些优点使多肽水凝胶成为各种生物医学应用的有趣候选物。特别是作为用于3D细胞培养和组织再生的可注射支架以及用于局部药物递送的储库。这篇综述集中在设计和制备注射剂方面的最新进展,热诱导的物理交联多肽水凝胶。组成的影响,强调了多肽片段的二级结构和手性对水凝胶的物理性质和生物降解的影响。此外,对水凝胶的生物医学应用的研究进行了深入的讨论。最后,提出了进一步开发用于实际应用的多肽水凝胶的主要挑战。
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