Dodla Mahesh Chandra, Bellamkonda Ravi V
Neurological Biomaterials and Therapeutics, Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, Atlanta, GA 30332-0535, USA.
Biomaterials. 2008 Jan;29(1):33-46. doi: 10.1016/j.biomaterials.2007.08.045. Epub 2007 Oct 10.
Anisotropic scaffolds of agarose hydrogels containing gradients of laminin-1 (LN-1) and nerve growth factor (NGF) molecules were used to promote sciatic nerve regeneration across a challenging 20mm nerve gap in rats. Step and continuous gradient anisotropic scaffolds were fabricated and characterized, and regeneration was compared to that in isotropic scaffolds with uniform concentrations of LN-1 and NGF and sciatic nerve grafts harvested from syngenic rats. Polysulfone tubular guidance channels were used to present the agarose-based scaffolds to the nerve stumps. Four months after implantation, regenerating axons were observed in animals implanted with anisotropic scaffolds with gradients of both LN-1 and NGF molecules and nerve grafts, but not in animals with isotropic scaffold implants. Also, the scaffolds with gradients of either LN-1 or NGF, with the other component being uniformly distributed in the scaffold, did not elicit axonal regeneration. The total number of myelinated axons was similar for the anisotropic scaffold and the nerve graft conditions, with the anisotropic scaffolds having a higher density of axons than the nerve grafts. Axonal diameter distribution was similar for the anisotropic scaffolds and the nerve grafts. The nerve grafts and anisotropic scaffolds resulted in better functional outcome compared to isotropic scaffolds as measured by the relative gastrocnemius muscle weight (RGMW). Additionally the state of neuromuscular junctions as assessed by pre- and post-synaptic staining revealed that both the anisotropic scaffolds performed as well as nerve grafts.
含有层粘连蛋白-1（LN-1）和神经生长因子（NGF）分子梯度的琼脂糖水凝胶各向异性支架，被用于促进大鼠20mm挑战性神经间隙的坐骨神经再生。制备并表征了阶梯式和连续梯度各向异性支架，并将再生情况与具有均匀浓度LN-1和NGF的各向同性支架以及从同基因大鼠获取的坐骨神经移植物中的再生情况进行比较。使用聚砜管状引导通道将基于琼脂糖的支架呈现给神经残端。植入四个月后，在植入含有LN-1和NGF分子梯度各向异性支架以及神经移植物的动物中观察到再生轴突，但在植入各向同性支架的动物中未观察到。此外，含有LN-1或NGF梯度且另一成分在支架中均匀分布的支架，未引发轴突再生。各向异性支架和神经移植物条件下有髓轴突的总数相似，各向异性支架的轴突密度高于神经移植物。各向异性支架和神经移植物的轴突直径分布相似。通过相对腓肠肌重量（RGMW）测量，与各向同性支架相比，神经移植物和各向异性支架产生了更好的功能结果。此外，通过突触前和突触后染色评估的神经肌肉接头状态表明，各向异性支架的表现与神经移植物一样好。
