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基于聚乙二醇的水凝胶在灵长类动物大脑中的生物相容性。

Biocompatibility of PEG-based hydrogels in primate brain.

作者信息

Bjugstad K B, Redmond D E, Lampe K J, Kern D S, Sladek J R, Mahoney M J

机构信息

Department Pediatrics, University Colorado Denver and Health Sciences Center, Aurora, CO 80045, USA.

出版信息

Cell Transplant. 2008;17(4):409-15.

Abstract

Degradable polymers have been used successfully in a wide variety of peripheral applications from tissue regeneration to drug delivery. These polymers induce little inflammatory response and appear to be well accepted by the host environment. Their use in the brain, for neural tissue reconstruction or drug delivery, also could be advantageous in treating neurodegenerative disorders. Because the brain has a unique immune response, a polymer that is compatible in the body may not be so in the brain. In the present study, polyethylene glycol (PEG)-based hydrogels were implanted into the striatum and cerebral cortex of nonhuman primates. Four months after implantation, brains were processed to evaluate the extent of astrogliosis and scaring, the presence of microglia/macrophages, and the extent of T-cell infiltration. Hydrogels with 20% w/v PEG implanted into the brain stimulated a slight increase in astrocytic and microglial/macrophage presence, as indicated by a small increase in glial fibrillary acidic protein (GFAP) and CD68 staining intensity. This increase was not substantially different from that found in the sham-implanted hemispheres of the brain. Staining for CD3+ T cells indicated no presence of peripheral T-cell infiltration. No gliotic scarring was seen in any implanted hemisphere. The combination of low density of GFAP-positive cells and CD68-positive cells, the absence of T cells, and the lack of gliotic scarring suggest that this level of immune response is not indicative of immunorejection and that the PEG-based hydrogel has potential to be used in the primate brain for local drug delivery or neural tissue regeneration.

摘要

可降解聚合物已成功应用于从组织再生到药物递送等各种外周应用中。这些聚合物引发的炎症反应很小,似乎能被宿主环境很好地接受。它们在大脑中用于神经组织重建或药物递送,在治疗神经退行性疾病方面也可能具有优势。由于大脑具有独特的免疫反应,一种在体内相容的聚合物在大脑中可能并非如此。在本研究中,将基于聚乙二醇(PEG)的水凝胶植入非人灵长类动物的纹状体和大脑皮层。植入四个月后,对大脑进行处理,以评估星形胶质细胞增生和瘢痕形成的程度、小胶质细胞/巨噬细胞的存在情况以及T细胞浸润的程度。植入大脑的含20% w/v PEG的水凝胶刺激星形细胞以及小胶质细胞/巨噬细胞的存在略有增加,这表现为胶质纤维酸性蛋白(GFAP)和CD68染色强度略有增加。这种增加与假手术植入的大脑半球中发现的增加没有实质性差异。CD3 + T细胞染色表明不存在外周T细胞浸润。在任何植入的半球中均未观察到胶质瘢痕形成。GFAP阳性细胞和CD68阳性细胞密度低、不存在T细胞以及缺乏胶质瘢痕形成,这些表明这种免疫反应水平并不表明免疫排斥,并且基于PEG的水凝胶有潜力用于灵长类动物大脑的局部药物递送或神经组织再生。

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