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Synthesis Strategies to Extend the Variety of Alginate-Based Hybrid Hydrogels for Cell Microencapsulation
Biomacromolecules ( IF 5.5 ) Pub Date : 2017-08-08 00:00:00 , DOI: 10.1021/acs.biomac.7b00665
Solène Passemard 1 , Luca Szabó 1 , François Noverraz 1 , Elisa Montanari 2 , Carmen Gonelle-Gispert 2 , Léo H. Bühler 2 , Christine Wandrey 1 , Sandrine Gerber-Lemaire 1
Affiliation  

The production of hydrogel microspheres (MS) for cell immobilization, maintaining the favorable properties of alginate gels but presenting enhanced performance in terms of in vivo durability and physical properties, is desirable to extend the therapeutic potential of cell transplantation. A novel type of hydrogel MS was produced by straightforward functionalization of sodium alginate (Na-alg) with heterotelechelic poly(ethylene glycol) (PEG) derivatives equipped with either end thiol or 1,2-dithiolane moieties. Activation of the hydroxyl moieties of the alginate backbone in the form of imidazolide intermediate allowed for fast conjugation to PEG oligomers through a covalent carbamate linkage. Evaluation of the modified alginates for the preparation of MS combining fast ionic gelation ability of the alginate carboxylate groups and slow covalent cross-linking provided by the PEG-end functionalities highlighted the influence of the chemical composition of the PEG-grafting units on the physical characteristics of the MS. The mechanical properties of the MS (resistance and shape recovery) and durability of PEG-grafted alginates in physiological environment can be adjusted by varying the nature of the end functionalities and the length of the PEG chains. In vitro cell microencapsulation studies and preliminary in vivo assessment suggested the potential of these hydrogels for cell transplantation applications.

中文翻译:

合成策略,以扩展基于藻酸盐的细胞微囊化混合水凝胶的种类。

为了扩大细胞移植的治疗潜能,期望生产用于细胞固定的水凝胶微球(MS),其保持藻酸盐凝胶的有利性质,但是在体内耐久性和物理性质方面表现出增强的性能。通过用装备有末端硫醇或1,2-二硫杂环戊酸酯基团的杂遥线型聚乙二醇(PEG)衍生物直接将藻酸钠(Na-alg)功能化,可以生产出新型的水凝胶MS。以咪唑化物中间体形式的藻酸盐骨架的羟基部分的活化允许通过共价氨基甲酸酯键快速缀合至PEG低聚物。结合藻酸盐羧酸盐基团的快速离子胶凝能力和PEG末端官能团提供的缓慢共价交联的改性藻酸盐制备MS的评估突出了PEG接枝单元的化学组成对物理特性的影响MS的。可以通过改变末端官能团的性质和PEG链的长度来调整MS的机械性能(电阻和形状恢复)和PEG接枝藻酸盐在生理环境中的耐久性。体外细胞微囊化研究和初步的体内评估表明,这些水凝胶在细胞移植中的潜力。
更新日期:2017-08-08
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