Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON M5S 3E5, Canada.
Biomed Mater. 2012 Apr;7(2):024101. doi: 10.1088/1748-6041/7/2/024101. Epub 2012 Mar 29.
Diseases and injuries of the central nervous system (CNS) including those in the brain, spinal cord and retina are devastating because the CNS has limited intrinsic regenerative capacity and currently available therapies are unable to provide significant functional recovery. Several promising therapies have been identified with the goal of restoring at least some of this lost function and include neuroprotective agents to stop or slow cellular degeneration, neurotrophic factors to stimulate cellular growth, neutralizing molecules to overcome the inhibitory environment at the site of injury, and stem cell transplant strategies to replace lost tissue. The delivery of these therapies to the CNS is a challenge because the blood-brain barrier limits the diffusion of molecules into the brain by traditional oral or intravenous routes. Injectable hydrogels have the capacity to overcome the challenges associated with drug delivery to the CNS, by providing a minimally invasive, localized, void-filling platform for therapeutic use. Small molecule or protein drugs can be distributed throughout the hydrogel which then acts as a depot for their sustained release at the injury site. For cell delivery, the hydrogel can reduce cell aggregation and provide an adhesive matrix for improved cell survival and integration. Additionally, by choosing a biodegradable or bioresorbable hydrogel material, the system will eventually be eliminated from the body. This review discusses both natural and synthetic injectable hydrogel materials that have been used for drug or cell delivery to the CNS including hyaluronan, methylcellulose, chitosan, poly(N-isopropylacrylamide) and Matrigel.
中枢神经系统（CNS）疾病和损伤，包括大脑、脊髓和视网膜的疾病和损伤，是毁灭性的，因为 CNS 的内在再生能力有限，目前可用的治疗方法无法提供显著的功能恢复。已经确定了几种有前途的治疗方法，旨在恢复至少部分丧失的功能，包括神经保护剂以阻止或减缓细胞退化、神经营养因子以刺激细胞生长、中和分子以克服损伤部位的抑制环境，以及干细胞移植策略以替代丢失的组织。将这些疗法递送到 CNS 是一个挑战，因为血脑屏障限制了通过传统的口服或静脉途径将分子扩散到大脑。可注射水凝胶具有克服向 CNS 递药相关挑战的能力，为治疗用途提供了微创、局部、空隙填充的平台。小分子或蛋白质药物可以分布在整个水凝胶中，然后水凝胶作为其在损伤部位的持续释放的储库。对于细胞递送，水凝胶可以减少细胞聚集并为改善细胞存活和整合提供粘附基质。此外，通过选择可生物降解或可生物吸收的水凝胶材料，该系统最终将从体内消除。本文综述了用于 CNS 药物或细胞递送的天然和合成可注射水凝胶材料，包括透明质酸、甲基纤维素、壳聚糖、聚（N-异丙基丙烯酰胺）和 Matrigel。
