Mehrotra Sumit, Lynam Daniel, Maloney Ryan, Pawelec Kendell M, Tuszynski Mark H, Lee Ilsoon, Chan Christina, Sakamoto Jeffrey
Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, Michigan 48824, MI (USA).
Adv Funct Mater. 2010 Jan 22;20(2):247-258. doi: 10.1002/adfm.200901172.
Axons of the adult central nervous system exhibit an extremely limited ability to regenerate after spinal cord injury. Experimentally generated patterns of axon growth are typically disorganized and randomly oriented. Support of linear axonal growth into spinal cord lesion sites has been demonstrated using arrays of uniaxial channels, templated with agarose hydrogel, and containing genetically engineered cells that secrete brain-derived neurotrophic factor (BDNF). However, immobilizing neurotrophic factors secreting cells within a scaffold is relatively cumbersome, and alternative strategies are needed to provide sustained release of BDNF from templated agarose scaffolds. Existing methods of loading the drug or protein into hydrogels cannot provide sustained release from templated agarose hydrogels. Alternatively, here it is shown that pH-responsive H-bonded poly(ethylene glycol)(PEG)/poly(acrylic acid)(PAA)/protein hybrid layer-by-layer (LbL) thin films, when prepared over agarose, provided sustained release of protein under physiological conditions for more than four weeks. Lysozyme, a protein similar in size and isoelectric point to BDNF, is released from the multilayers on the agarose and is biologically active during the earlier time points, with decreasing activity at later time points. This is the first demonstration of month-long sustained protein release from an agarose hydrogel, whereby the drug/protein is loaded separately from the agarose hydrogel fabrication process.
成体中枢神经系统的轴突在脊髓损伤后再生能力极其有限。实验诱导产生的轴突生长模式通常杂乱无章且方向随机。使用以琼脂糖水凝胶为模板、含有分泌脑源性神经营养因子（BDNF）的基因工程细胞的单轴通道阵列，已证明可支持轴突线性生长进入脊髓损伤部位。然而，将分泌神经营养因子的细胞固定在支架内相对繁琐，需要替代策略来实现BDNF从模板化琼脂糖支架中的持续释放。现有的将药物或蛋白质加载到水凝胶中的方法无法实现从模板化琼脂糖水凝胶中的持续释放。在此，研究表明，当在琼脂糖上制备时，pH响应性氢键结合的聚乙二醇（PEG）/聚丙烯酸（PAA）/蛋白质逐层（LbL）薄膜在生理条件下可实现蛋白质持续释放超过四周。溶菌酶是一种大小和等电点与BDNF相似的蛋白质，它从琼脂糖上的多层膜中释放出来，在早期时间点具有生物活性，后期活性降低。这是首次证明从琼脂糖水凝胶中实现长达一个月的蛋白质持续释放，其中药物/蛋白质是与琼脂糖水凝胶制备过程分开加载的。
