Synthesis of Polymerizable Superoxide Dismutase Mimetics to Reduce Reactive Oxygen Species Damage in Transplanted Biomedical Devices
Synthesis of Polymerizable Superoxide Dismutase Mimetics to Reduce Reactive Oxygen Species Damage in Transplanted Biomedical Devices
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DOI：
10.1002/adfm.200800566
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发表时间：
2008-10-23
影响因子：
19
通讯作者：
Anseth, Kristi S.
中科院分区：
文献类型：
--
作者：
Cheung, Charles Y.;McCartney, Suzanne J.;Anseth, Kristi S.
合成了一种新的可聚合的超氧化物歧化酶（SOD）模拟物金属卟啉大分子单体，以最小化与组织移植和生物材料植入相关的炎性损伤，例如使用包封的胰岛治疗I型糖尿病（TIDM）。这种功能性SOD模拟物Mn（III）四[1-（3-丙烯酰氧基-丙基）-4-吡啶基]卟啉（MnTPPyP-Acryl）与聚（乙二醇）二丙烯酸酯（PEGDA）共聚并交联以形成水凝胶网络，其可以积极地减少与生物材料植入相关的活性氧（ROS）损伤。用MnTPPyP-丙烯酰基大分子单体的溶液相活性测定显示出与MnTMPyP（不可聚合的市售SOD模拟物）相当的SOD活性。这项工作还描述了一种新的，简单的，廉价的固相测定系统，开发的PEGDA水凝胶内聚合的MnTPPyP-Acryl大分子单体的活性进行评估，这有可能满足现有的空白与生化工具可用于测试其他固定的ROS拮抗剂的发展。使用这种新的测定系统，含有高达0.25摩尔% MnTPPyP-Acryl的水凝胶显示出显著更高水平的SOD活性，而与无活性MnTPPyP-Acryl大分子单体聚合的对照水凝胶仅显示出背景水平的活性。在聚合后保持100%SOD活性至少72小时后，证明了重复使用这种水凝胶装置以持续降低超氧阴离子浓度的潜力。这些结果证明了可聚合SOD模拟物可能具有整合到医疗装置中的潜力，用于在移植时（例如在递送包封的胰岛期间）使炎性损伤最小化。
A new polymerizable superoxide dismutase (SOD) mimetic metalloporphyrin macromer was synthesized to minimize inflammatory damage associated with tissue transplantation and biomaterial implantation, such as the use of encapsulated pancreatic islets for the treatment of type I diabetes mellitus (TIDM). This functional SOD mimetic, Mn(III) Tetrakis[1-(3-acryloxy-propyl)-4-pyridyl] porphyrin (MnTPPyP-Acryl), was copolymerized and crosslinked with poly(ethylene glycol) diacrylate (PEGDA) to form hydrogel networks that may actively reduce reactive oxygen species (ROS) damage associated with biomaterial implantation. Solution phase activity assays with MnTPPyP-Acryl macromers showed comparable SOD activity to MnTMPyP, a non-polymerizable commercially available SOD mimetic. This work also describes the development of a new, simple, and inexpensive solid phase assay system that was developed to assess the activity of MnTPPyP-Acryl macromers polymerized within PEGDA hydrogels, which has the potential to fulfill an existing void with the biochemical tools available for testing other immobilized ROS antagonists. With this new assay system, hydrogels containing up to 0.25 mol% MnTPPyP-Acryl showed significantly higher levels of SOD activity, whereas control hydrogels polymerized with inactive MnTPPyP-Acryl macromers showed only background levels of activity. The potential for repeated use of such hydrogel devices to consistently reduce superoxide anion concentrations was demonstrated upon retention of 100% SOD activity for at least 72 h post-polymerization. These results demonstrate the potential that polymerizable SOD mimetics may have for integration into medical devices for the minimization of inflammatory damage upon transplantation, such as during the delivery of encapsulated pancreatic islets.