Mechanically engineered hydrogel scaffolds for axonal growth and angiogenesis after transplantation in spinal cord injury
Mechanically engineered hydrogel scaffolds for axonal growth and angiogenesis after transplantation in spinal cord injury
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DOI：
10.3171/spi.2004.1.3.0322
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发表时间：
2004-10-01
影响因子：
2.8
通讯作者：
Lowman, A
中科院分区：
文献类型：
--
作者：
Bakshi, A;Fisher, O;Lowman, A
物体。脊髓损伤(SCI)是一个复杂的病理实体，其治疗需要多管齐下。整合不同SCI治疗策略的一种方法是开发能够以协同方式提供治疗的可植入支架。许多研究人员已经开发出可植入的“桥”，但这种支架的一个重要特性--即与宿主组织的机械兼容性--被忽视了。在这项研究中，作者评估了植入机械匹配的水凝胶支架治疗脊髓损伤的结果。采用热引发自由基溶液聚合法制备了一种不可生物降解的水凝胶--聚甲基丙烯酸羟乙酯(PHEMA)。将12只成年SD大鼠分为两组，每组12只。损伤后植入PHEMA或PHEMA浸泡1杯脑源性神经营养因子(BDNF)。致伤后1、2、4周每组各处死4只大鼠。免疫荧光染色检测植入支架内和周围的瘢痕形成、细胞炎症反应、胶质增生、血管生成和轴突生长。植入的PHEMA含水率为85%，压缩模数为3~4kPa，与脊髓相匹配。植入的PHEMA引起了轻微的细胞炎症反应，4周后消失，基质周围的疤痕也很少。在PHEMA中观察到大量的血管生成。浸泡在BDNF中的PHEMA可促进轴突穿透凝胶。作者认为，机械工程化PHEMA被宿主组织所接受，可作为持续给药的平台，促进脊髓损伤后轴突生长和功能恢复。
Object. Spinal cord injury (SCI) is a complex pathological entity, the treatment of which requires a multipronged approach. One way to integrate different therapeutic strategies for SCI is to develop implantable scaffolds that can deliver therapies in a synergistic manner. Many investigators have developed implantable "bridges," but an important property of such scaffolds-that is, mechanical compatibility with host tissues-has been neglected. In this study, the authors evaluated the results of implanting a mechanically matched hydrogel-based scaffold to treat SCI.Methods. A nonbiodegradable hydrogel, poly(2-hydroxyethylmethacrylate) (PHEMA), was engineered using thermally initiated free radical solution polymerization. Two groups of 12 adult Sprague-Dawley rats underwent partial cervical hemisection injury followed by implantation of either PHEMA or PHEMA soaked in 1 mug of brain-derived neurotrophic factor (BDNF). Four rats from each group were killed 1, 2, or 4 weeks after induction of the injury. Immunofluorescence staining was performed to determine the presence of scarring, cellular inflammatory responses, gliosis, angiogenesis, and axonal growth in and around the implanted scaffolds.Conclusions. The implanted PHEMA with 85% water content had a compressive modulus of 3 to 4 kPa, which matched the spinal cord. Implanted PHEMA elicited modest cellular inflammatory responses that disappeared by 4 weeks and minimal scarring was noted around the matrix. Considerable angiogenesis was observed in PHEMA. and PHEMA soaked in BDNF promoted axonal penetration into the gel. The authors conclude that mechanically engineered PHEMA is well accepted by host tissues and might be used as a platform for sustained drug delivery to promote axonal growth and functional recovery after SCI.