Biocompatibility of poly(ethylene glycol)-based hydrogels in the brain: An analysis of the glial response across space and time

Biocompatibility of poly(ethylene glycol)-based hydrogels in the brain: An analysis of the glial response across space and time
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DOI:
10.1002/jbm.a.32809
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发表时间:
2010-10-01
影响因子:
4.9
通讯作者:
Mahoney, M.
Mahoney, M.
中科院分区:
工程技术3区
文献类型:
--
作者:
Bjugstad, K. B.;Lampe, K.;Mahoney, M.

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基于聚乙二醇或 PEG 的水凝胶为组织工程和中枢神经系统 (CNS) 内的药物控释提供了有用的方法。为了取得成功,必须充分了解植入物的局部神经炎症反应。为此,重点是检查基于 PEG 的水凝胶植入大脑后小胶质细胞和星形胶质细胞的局部募集和激活。由于它们具有临床相关性并且可能对脑组织产生不同的影响,因此对具有不同质量损失特征的水凝胶进行了检查。在所有时间点,假手术动物中的针刺比水凝胶条件下引起更大的星形胶质细胞反应。随后的星形胶质细胞反应随降解速度而变化。在更缓慢的降解和非降解条件下存在减弱的响应。与假手术相比,水凝胶条件减弱了植入后一周内的急性小胶质细胞反应。到 56 天时,假手术中的小胶质细胞水平下降到低于缓慢降解和不可降解凝胶中观察到的反应,并且随着时间的推移保持恒定。尽管基于 PEG 的水凝胶的炎症反应很复杂,具体取决于降解率,但急性小胶质细胞反应和长期星形胶质细胞反应的强度减弱,表明这些材料可用于将药物和细胞递送至中枢神经系统。 (C) 2010 Wiley periodicals, Inc. J Biomed Mater Res Part A: 95A: 79-91, 2010。
Poly(ethylene glycol) or PEG-based hydrogels provide a useful methodology for tissue engineering and the controlled-release of drugs within the central nervous system (CNS). To be successful, the local neuroinflammatory response to an implant must be well understood. Toward this end, the focus was to examine the localized recruitment and activation of microglia and astrocytes following implantation of PEG-based hydrogels in the brain. Because they are of clinical relevance and may impact brain tissue differently, hydrogels with different mass loss profiles were examined. At all time points, a needle penetration in sham animals evoked a greater astrocytic response than hydrogel conditions. The astrocyte response that ensued varied with degradation rate. An attenuated response was present in more slowly degrading and nondegrading conditions. Relative to sham, hydrogel conditions attenuated the acute microglial response during the week after implant. By 56 days, microglial levels in shams decreased below the observed response in slowly degrading and nondegradable gels, which remained constant overtime. Although the inflammatory response to PEG-based hydrogels was complex depending on degradation rates, the magnitude of the acute microglia response and the long-term astrocyte response were attenuated suggesting the use of these materials for drug and cell delivery to the CNS. (C) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 95A: 79-91, 2010.