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功能化嵌段共聚酯的合成,其源自乳酸和大环内酯,用于骨组织再生。

Synthesis of Functionalized Triblock Copolyesters Derived from Lactic Acid and Macrolactones for Bone Tissue Regeneration.

机构信息

Artificial Nature S.L., Baldiri i Reixac 10, Barcelona, 08028, Spain.

Departament d'Enginyeria Química, Universitat Politècnica de Catalunya, ETSEIB, Diagonal 647, Barcelona, 08028, Spain.

出版信息

Macromol Biosci. 2023 Jul;23(7):e2300066. doi: 10.1002/mabi.202300066. Epub 2023 Apr 25.

DOI:10.1002/mabi.202300066
PMID:37031382
Abstract

Synthetic and functional grafts are a great alternative to conventional grafts. They can provide a physical support and the precise signaling for cells to heal damaged tissues. In this study, a novel RGD peptide end-functionalized poly(ethylene glycol)-b-poly(lactic acid)-b-poly(globalide)-b-poly(lactic acid)-b-poly(ethylene glycol) (RGD-PEG-PLA-PGl-PLA-PEG-RGD) is synthetized and used to prepare functional scaffolds. The PGl inner block is obtained by enzymatic ring-opening polymerization of globalide. The outer PLA blocks are obtained by ring-opening polymerization of both, l-lactide or a racemic mixture, initiated by the α-ω-telechelic polymacrolactone. The presence of PGl inner block enhances the toughness of PLA-based scaffolds, with an increase of the elongation at break up to 300% when the longer block of PGl is used. PLA-PGl-PLA copolymer is coupled with α-ω-telechelic PEG diacids by esterification reaction. PEGylation provides hydrophilic scaffolds as the contact angle is reduced from 114° to 74.8°. That difference improves the contact between the scaffolds and the culture media. Moreover, the scaffolds are functionalized with RGD peptides at the surface significantly enhancing the adhesion and proliferation of bone marrow-derived primary mesenchymal stem cells and MC3T3-E1 cell lines in vitro. These results place this multifunctional polymer as a great candidate for the preparation of temporary grafts.

摘要

合成和功能化移植物是传统移植物的绝佳替代品。它们可以为细胞提供物理支撑和精确的信号,以促进受损组织的修复。在这项研究中,我们合成了一种新型的 RGD 肽端功能化聚乙二醇-b-聚乳酸-b-聚(丙交酯)-b-聚乳酸-b-聚乙二醇(RGD-PEG-PLA-PGl-PLA-PEG-RGD),并将其用于制备功能化支架。PGl 内嵌段是通过丙交酯的酶开环聚合得到的。外 PLA 嵌段是通过长链 PLA 开环聚合得到的,引发剂是α-ω-端官能聚内酯。PGl 内嵌段的存在增强了 PLA 基支架的韧性,当使用较长的 PGl 嵌段时,断裂伸长率增加了 300%。PLA-PGl-PLA 共聚物通过酯化反应与α-ω-端官能 PEG 二酸偶联。PEG 化提供了亲水性支架,因为接触角从 114°降低到 74.8°。这种差异改善了支架与培养基之间的接触。此外,支架表面通过 RGD 肽进行功能化,显著提高了骨髓来源的原代间充质干细胞和 MC3T3-E1 细胞系在体外的黏附和增殖能力。这些结果表明,这种多功能聚合物是制备临时移植物的理想候选材料。

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