可控释放TGF-β/BMP7因子的纳米自组装多肽修复髓核摘除术后椎间盘退变的研究

The amount of adults group undergoing the intervertebral disc herniation is increasing under the high pressure and the change of living style. The discectomy is the major therapy method to intervertebral disc herniation. However,the degeneration of intervertebral disc and the unstability of segments are the severe complication after discectomy.The medical problem needed to be resolved imperiously is to explore the new means of regenerating the nucleus pulposus after discectomy. Therefore,in this study, we shall construct the self-assembling peptide nanofiber scaffold RADA16-I for controlled the release of Transforming growth factor β（TGF-β）and Bone morphogenetic protein 7(BMP-7).Then tissue engineering nucleus pulposus will be constucted by the RADA16-I for controlled the release of TGF-β/BMP-7 and autologous adipose-derived stem cells (ADSCs). This tissue engineering nucleus pulposus will be planted into the space of intervertebral disc after discectomy. According to the controlled release of TGF-β/BMP-7 in coordination with the local microenvironment, ADSCs will differentiate toward nuclues pulposus-like cells which mainly expressing aggrecan and collagen Ⅱ. The tissue engineering nuclues pulposus will regenerate the nuclues pulposus which could restore the height of disc and the biological function. This study is going to provide a clinical possibility: tissue engineering intervertebral disc using ADSCs seeded onto RADA16-I for controlled the release of TGF-β/BMP-7 for IVD regeneration in vivo after discectomy.

随着生活压力的增加，生活习惯的改变，全球青壮年人群中罹患腰椎间盘突出性疾病的比例逐年增加，单纯髓核摘除术是其最主要的治疗方法。然而单纯髓核摘除后出现的摘除节段椎间盘退变、节段不稳是其主要并发症，寻求一种单纯髓核摘除后的椎间盘再生方法是目前亟待解决的医学难题。本项目研究拟利用纳米自组装多肽RADA16-I预先承载具有诱导干细胞向髓核细胞分化的转化生长因子β（TGF-β）及骨形成蛋白7(BMP-7)，同Beagle犬自体获得的脂肪干细胞（ADSC）体外组装成细胞支架复合物，将其填充于单纯髓核摘除后的椎间盘内空隙处，通过RADA16-I支架材料中TGF-β及BMP-7的缓慢释放，协同椎间盘的局部微环境，体内诱导ADSCs分化为髓核样细胞，最终生成具有维持椎间盘高度和承重等生理功能的椎间盘组织，为探寻单纯髓核摘除后,促进髓核再生修复，进而阻止椎间盘进一步退变的治疗方法奠定基础。

随着生活压力的增加，生活习惯的改变，全球青壮年人群中罹患腰椎间盘突出性疾病的比例逐年增加，单纯髓核摘除术是其最主要的治疗方法。然而单纯髓核摘除后出现的摘除节段椎间盘退变、节段不稳是其主要并发症，寻求一种单纯髓核摘除后的椎间盘再生方法是目前亟待解决的医学难题。本项目研究利用纳米自组装多肽RADA16-I预先承载具有诱导干细胞向髓核细胞分化的转化生长因子β（TGF-β）及骨形成蛋白7(BMP-7)，同Beagle犬自体获得的脂肪干细胞（ADSC）体外组装成细胞支架复合物，将其填充于单纯髓核摘除后的椎间盘内空隙处，通过RADA-I支架材料中TGF-β及BMP-7的缓慢释放，协同椎间盘的局部微环境，体内诱导ADSCs分化为髓核样细胞，研究结果显示：这种能缓慢释放细胞因子的组织工程髓核能够明显延缓单纯髓核摘除后,手术间盘进一步退变。