Department of Orthopedic Surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
J Biomed Mater Res A. 2011 Jan;96(1):13-20. doi: 10.1002/jbm.a.32946. Epub 2010 Oct 14.
Many neurotrophic factors have been shown to promote neurite outgrowth by improving the microenvironment that is required for nerve regeneration. However, the delivery of these bioactive agents to the nerve injury site, as well as effective and local release, remains a challenging problem. We have developed a novel composite nerve conduit comprised of poly(lactic acid-caprolactone) (P(LLA-CL)) and nerve growth factor (NGF). This was developed from core-shell structured biodegradable nanofibers, which were fabricated by coaxial electrospinning of P(LLA-CL) for the shell and bovine serum albumin (BSA) or BSA/NGF for the core. In rats, gaps of 10-mm long sciatic nerves were bridged using an autograft, an empty P(LLA-CL) conduit, a NGF injection P(LLA-CL) conduit, a P(LLA-CL)/NGF composite conduit, respectively. Regenerated nerve fibers were harvested and morphological and functional evaluation of nerve regeneration was performed at 12 weeks postsurgery. Although partial biodegradation and small cracks in the conduits were observed, the conduit outlines remained intact for 12 weeks after surgery. Based on functional and histological observations, the number and arrangement of regenerated nerve fibers, myelination, and nerve function reconstruction was similar in the P(LLA-CL)/NGF conduit group to that of the nerve autograft group (p > 0.05), but was significantly greater to the empty P(LLA-CL) and injection NGF P(LLA-CL) conduit groups (both p < 0.05). Therefore, the composite P(LLA-CL)/NGF conduit, which exhibited favorable mechanical properties and biocompatibility, could effectively promote sciatic nerve regeneration in rats.
许多神经营养因子已被证明通过改善神经再生所需的微环境来促进轴突生长。然而,将这些生物活性物质递送到神经损伤部位以及有效和局部释放仍然是一个具有挑战性的问题。我们开发了一种由聚(乳酸-己内酯)(P(LLA-CL))和神经生长因子(NGF)组成的新型复合神经导管。该导管由核壳结构的可生物降解纳米纤维组成,通过 P(LLA-CL)壳的同轴电纺和牛血清白蛋白(BSA)或 BSA/NGF 芯的同轴电纺来制备。在大鼠中,使用自体移植物、空 P(LLA-CL)导管、NGF 注射 P(LLA-CL)导管、P(LLA-CL)/NGF 复合导管分别桥接 10mm 长坐骨神经间隙。手术后 12 周收获再生神经纤维,并进行神经再生的形态和功能评估。尽管观察到导管部分降解和小裂缝,但手术后 12 周导管轮廓仍保持完整。基于功能和组织学观察,再生神经纤维的数量和排列、髓鞘形成和神经功能重建在 P(LLA-CL)/NGF 导管组与神经自体移植物组相似(p>0.05),但明显优于空 P(LLA-CL)和注射 NGF P(LLA-CL)导管组(均 p<0.05)。因此,表现出良好的机械性能和生物相容性的复合 P(LLA-CL)/NGF 导管可以有效促进大鼠坐骨神经再生。