Sustained Delivery of Dibutyryl Cyclic Adenosine Monophosphate to the Transected Spinal Cord Via Oligo [(Polyethylene Glycol) Fumarate] Hydrogels
Sustained Delivery of Dibutyryl Cyclic Adenosine Monophosphate to the Transected Spinal Cord Via Oligo [(Polyethylene Glycol) Fumarate] Hydrogels
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DOI：
10.1089/ten.tea.2010.0396
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发表时间：
2011-05-01
影响因子：
4.1
通讯作者：
Windebank, Anthony J.
中科院分区：
文献类型：
--
作者：
Rooney, Gemma E.;Knight, Andrew M.;Windebank, Anthony J.
本研究描述了使用寡聚[（聚乙二醇）富马酸盐]（OPF）水凝胶支架作为车辆持续交付的二丁酰环磷酸腺苷（dbcAMP）横断脊髓。将dbcAMP包封在聚（乳酸-共-乙醇酸）（PLGA）微球中，微球嵌入支架结构中。使用PC 12细胞中的神经突生长测定和通过递送到OPF七通道支架内的横断脊髓来评估释放的dbcAMP的功能，所述支架已装载有雪旺细胞或间充质干细胞（MSC）。我们的研究结果表明，包封的dbcAMP在微球导致延长释放和持续的功能在体外。然后将这些微球成功地掺入OPF支架中并植入横断的胸脊髓中。持续递送dbcAMP在雪旺细胞存在下抑制轴突再生，但挽救了MSC诱导的轴突再生抑制。dbcAMP还显示在MSC存在下减少毛细血管形成，这与显著的功能改善相结合。我们的研究结果证明了将PLGA微球技术用于脊髓横断研究的可行性。它代表了一种新的持续输送机制在横断脊髓，并提供了一个平台，为潜在的其他治疗药物的交付。
This study describes the use of oligo [(polyethylene glycol) fumarate] (OPF) hydrogel scaffolds as vehicles for sustained delivery of dibutyryl cyclic adenosine monophosphate (dbcAMP) to the transected spinal cord. dbcAMP was encapsulated in poly(lactic-co-glycolic acid) (PLGA) microspheres, which were embedded within the scaffolds architecture. Functionality of the released dbcAMP was assessed using neurite outgrowth assays in PC12 cells and by delivery to the transected spinal cord within OPF seven channel scaffolds, which had been loaded with Schwann cells or mesenchymal stem cells (MSCs). Our results showed that encapsulation of dbcAMP in microspheres lead to prolonged release and continued functionality in vitro. These microspheres were then successfully incorporated into OPF scaffolds and implanted in the transected thoracic spinal cord. Sustained delivery of dbcAMP inhibited axonal regeneration in the presence of Schwann cells but rescued MSC-induced inhibition of axonal regeneration. dbcAMP was also shown to reduce capillary formation in the presence of MSCs, which was coupled with significant functional improvements. Our findings demonstrate the feasibility of incorporating PLGA microsphere technology for spinal cord transection studies. It represents a novel sustained delivery mechanism within the transected spinal cord and provides a platform for potential delivery of other therapeutic agents.