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按需调控降解速率的基于柠檬酸盐的聚酯弹性体。

Citrate-Based Polyester Elastomer with Artificially Regulatable Degradation Rate on Demand.

机构信息

Key Laboratory of High Performance Polymer Material and Technology of MOE, Department of Polymer Science and Engineering, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China.

State Key Laboratory of Pharmaceutical Biotechnology, Department of Biotechnology and Pharmaceutical Sciences, School of Life Sciences, Nanjing University, Nanjing 210023, P. R. China.

出版信息

Biomacromolecules. 2023 Sep 11;24(9):4123-4137. doi: 10.1021/acs.biomac.3c00479. Epub 2023 Aug 16.

Abstract

Citrate-based polymers are commonly used to create biodegradable implants. In an era of personalized medicine, it is highly desired that the degradation rates of citrate-based implants can be artificially regulated as required during clinical applications. Unfortunately, current citrate-based polymers only undergo passive degradation, which follows a specific degradation profile. This presents a considerable challenge for the use of citrate-based implants. To address this, a novel citrate-based polyester elastomer (POCSS) with artificially regulatable degradation rate is developed by incorporating disulfide bonds (S-S) into the backbone chains of the crosslinking network of poly(octamethylene citrate) (POC). This POCSS exhibits excellent and tunable mechanical properties, notable antibacterial properties, good biocompatibility, and low biotoxicity of its degradation products. The degradation rate of the POCSS can be regulated by breaking the S-S in its crosslinking network using glutathione (GSH). After a period of subcutaneous implantation of POCSS scaffolds in mice, the degradation rate eventually increased by 2.46 times through the subcutaneous administration of GSH. Notably, we observed no significant adverse effects on its surrounding tissues, the balance of the physiological environment, major organs, and the health status of the mice during degradation.

摘要

基于柠檬酸盐的聚合物常用于制造可生物降解的植入物。在个性化医疗时代,人们非常希望在临床应用中能够根据需要人为调节基于柠檬酸盐的植入物的降解速率。不幸的是,目前的基于柠檬酸盐的聚合物仅经历被动降解,遵循特定的降解曲线。这对基于柠檬酸盐的植入物的使用带来了相当大的挑战。为了解决这个问题,通过在交联网络的主链中引入二硫键(S-S),开发了一种新型的具有可人工调节降解率的基于柠檬酸盐的聚酯弹性体(POCSS)。聚(辛基柠檬酸盐)(POC)的交联网络。这种 POCSS 具有出色且可调的机械性能、显著的抗菌性能、良好的生物相容性以及其降解产物的低生物毒性。可以通过使用谷胱甘肽(GSH)破坏其交联网络中的 S-S 来调节 POCSS 的降解速率。在小鼠皮下植入 POCSS 支架一段时间后,通过皮下给予 GSH,其降解速率最终增加了 2.46 倍。值得注意的是,在降解过程中,我们没有观察到其周围组织、生理环境的平衡、主要器官以及小鼠健康状况有任何明显的不良影响。

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