Poly(epsilon-caprolactone) and poly (L-lactic-co-glycolic acid) degradable polymer sponges attenuate astrocyte response and lesion growth in acute traumatic brain injury.

Darice Y Wong, Scott J Hollister, Paul H Krebsbach, Christopher Nosrat
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引用次数: 71

Abstract

This study evaluated the response of rat brain to 2 degradable polymers (poly (L-lactic-co-glycolic acid) (PLGA), and poly(epsilon-caprolactone) (PCL)), two common materials in tissue engineering. PLGA has been extensively studied in the brain for controlled drug release as injectable microspheres and is generally accepted as biocompatible in that capacity. Biocompatibility in other forms and for different functions in the brain has not been widely studied. PCL was chosen as an alternative to PLGA for its slower degradation and less-acidic pH upon degradation. Porous scaffolds were made from both polymers and implanted into rat cerebral cortex for 1 and 4 weeks. Morphology, defect size, activation of microglia (OX-42) and astrocytes (glial fibrillary acidic protein (GFAP)), infiltration of activated macrophages (major histocompatibility complex (MHC)-II), and ingrowth of neurons (beta-tubulin type III (Tuj-1)) and progenitor cells (nestin) were analyzed using hematoxylin and eosin staining and immunofluorescence. PCL induced a lower inflammatory response than PLGA, as demonstrated by lower MHC-II and GFAP expression and greater ingrowth. Both polymers alleviated astrocytic activation and prevented enlargement of the defect. Tuj-1-, nestin-, and GFAP-positive cells were observed growing on both polymers at the peripheries of the sponge implants, demonstrating their permissiveness to neural ingrowth. These findings suggest that both polymers attenuate secondary death and scarring and that PCL might have advantages over PLGA.

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聚(ε -己内酯)和聚(l -乳酸-羟基乙酸)可降解聚合物海绵可减轻急性创伤性脑损伤中星形胶质细胞的反应和病变的生长。
本研究评估了大鼠脑对两种可降解聚合物(聚l -乳酸-羟基乙酸)(PLGA)和聚epsilon-己内酯(PCL))的反应,这两种聚合物是组织工程中常用的材料。PLGA作为可注射微球在大脑中被广泛研究,用于控制药物释放,并被普遍认为具有生物相容性。其他形式的生物相容性和大脑中不同功能的生物相容性尚未得到广泛研究。选择PCL作为PLGA的替代品,因为它的降解速度较慢,降解时的酸性pH值较低。将这两种聚合物制成多孔支架,分别植入大鼠大脑皮层1周和4周。采用苏木精染色、伊红染色和免疫荧光分析形态学、缺陷大小、小胶质细胞(OX-42)和星形胶质细胞(胶质纤维酸性蛋白(GFAP))的活化、活化巨噬细胞(主要组织相容性复合体(MHC)-II)的浸润、神经元(β -微管蛋白III型(Tuj-1))和祖细胞(巢蛋白)的向内生长。与PLGA相比,PCL诱导的炎症反应更低,MHC-II和GFAP表达更低,生长更大。这两种聚合物都减轻了星形细胞的激活,防止了缺陷的扩大。Tuj-1、nestin和gfap阳性细胞在海绵植入物周围的两种聚合物上生长,表明它们允许神经向内生长。这些发现表明,这两种聚合物都能减轻继发性死亡和疤痕,PCL可能比PLGA有优势。
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Tissue engineering
Tissue engineering CELL & TISSUE ENGINEERING-BIOTECHNOLOGY & APPLIED MICROBIOLOGY
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