N-Hydroxysuccinimide Bifunctionalized Triblock Cross-Linker Having Hydrolysis Property for a Biodegradable and Injectable Hydrogel System
N-Hydroxysuccinimide Bifunctionalized Triblock Cross-Linker Having Hydrolysis Property for a Biodegradable and Injectable Hydrogel System
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DOI：
10.1021/acsbiomaterials.9b00218
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发表时间：
2019-11-01
影响因子：
5.8
通讯作者：
Otsuka, Hidenori
中科院分区：
文献类型：
--
作者：
Ishikawa, Shohei;Matsukuma, Daisuke;Otsuka, Hidenori
生物相容性、可降解性和可注射性的水凝胶的设计对于实现安全有效的组织工程具有吸引力。本文设计了一种N-羟基琥珀酰亚胺（NHS）酯封端的阿坝三嵌段共聚物（NHS-PEG-b-PLA-b-PEG-NHS），该共聚物由聚乙二醇（PEG）作为亲水性A链段和聚（DL-丙交酯）（PLA）作为具有水解性质的B链段组成，作为具有胺基的聚合物链段的交联剂，用于可注射和可降解的水凝胶的构建。广泛接受的可水解片段的PLA结构域是固有疏水性的，并且在PLA末端上简单引入NHS基团在水性环境中不会具有高反应性以构建可注射水凝胶。因此，在该设计中，引入亲水性PEG作为A片段，以通过增加迁移率来增加接头末端的NHS基团的反应性。为了证明作为用于构建可降解和可注射水凝胶的交联剂的性质，将羧甲基壳聚糖（CH）（其是具有胺基的聚合物片段）和NHS-PEG-b-PLA-b-PEG-NHS溶液混合以在生理条件下形成水凝胶（CH/PEG-PLA-PEG）。CH/PEG-PLA-PEG水凝胶的形成在混合溶液后的分钟级时间内进行，表明NHS-PEG-b-PLA-b-PEG-NHS适用于构建具有时间依赖性凝胶化性质的可注射水凝胶系统的交联剂。观察到所获得的CH/PEG-PLA-PEG水凝胶的降解，而没有观察到由NHS-PEG-NHS和CH制备的CH/PEG的降解，这吸引了基于PLA结构域的水解的CH/PEG-PLA-PEG水凝胶的降解性质。此外，与CH/PEG相比，包埋在CH/PEG-PLA-PEG水凝胶中的软骨细胞促进胶原合成。这些证明表明所设计的NHS-PEG-b-PLA-b-PEG-NHS是一种有前途的交联剂，用于构建可注射和可降解的水凝胶，并最终促进水凝胶作为组织再生支架的性能。
The design of biocompatible, degradable, and injectable hydrogel has been attractive for achievement of safe and efficient tissue engineering. Herein, we designed a N-hydroxysuccinimide (NHS) ester-terminated ABA triblock copolymer composed of poly(ethylene glycol) (PEG) as hydrophilic A segments and poly(DL-lactide) (PLA) as B segment having hydrolysis property (NHS-PEG-b-PLA-b-PEG-NHS) to be a cross-linker of polymer segments having amine groups for facile construction of injectable and degradable hydrogel. The PLA domain, which is widely accepted hydrolyzable segments, is inherently hydrophobic and simple introduction of the NHS group on the ends of PLA would not have high reactivity in aqueous milieu to construct injectable hydrogel. Thus, in this design, hydrophilic PEG was introduced as A segments to increase the reactivity of NHS groups at the ends of linkers by increasing the mobility. To demonstrate the property as a cross-linker for constructing degradable and injectable hydrogel, carboxylmethyl chitosan (CH), which is a polymer segment having amine groups, and NHS-PEG-b-PLA-b-PEG-NHS solutions were mixed to form the hydrogel (CH/PEG-PLA-PEG) under physiological condition. The formation of CH/PEG-PLA-PEG hydrogel proceeded within minute-order period after mixing the solutions, suggesting NHS-PEG-b-PLA-b-PEG-NHS is applicable to the cross linker for construction of injectable hydrogel system with time-dependent gelation property. Degradation of the obtained CH/PEG-PLA-PEG hydrogel was observed, whereas that of CH/PEG, which was prepared from NHS-PEG-NHS and CH, was not observed, appealing the degradation property of the CH/PEG-PLA-PEG hydrogel based on hydrolysis of the PLA domain. Furthermore, chondrocytes embedded in CH/PEG-PLA-PEG hydrogels promoted collagen synthesis compared to CH/PEG. These demonstrations indicate the designed NHS-PEG-b-PLA-b-PEG-NHS is a promising cross-linker to construct the injectable and degradable hydrogel and eventually promote hydrogel performance as a tissue regeneration scaffold.