Sa12b和BMP7修饰的功能化自组装多肽水凝胶材料修复椎间盘退变的应用基础研究

椎间盘退变是引起颈腰痛的主要病因。临床以对“症”治疗为主，而非对“因”治疗。组织工程髓核可促进髓核细胞再生，有望实现对“因”治疗。但现有组织工程髓核均未考虑椎间盘退变后微环境改变对其影响，导致体内与体外的实验结果存在巨大差异。椎间盘退变微环境的改变会抑制细胞生物学活性。我们前期研究发现，这些微环境中以酸环境的抑制作用最为显著，且通过酸离子敏感通道发挥效应。因此，构建一种可克服酸环境的组织工程髓核是治疗关键。RADA16是一种可体内自组装成水凝胶的多肽材料，在其C末端插入特殊功能的短肽可构建组织特异性多肽材料。为此，我们拟将酸离子敏感通道的阻滞剂Sa12b与RADA16结合构建功能化多肽RAD/SA1，观察其材料特性、生物相容性、体外和体内生物活性及作用机制。此外，再将其与我们前期利用BMP7构建的多肽RAD/KPS混合，观察两者的协同作用，从而为椎间盘退变的修复提供新的思路和方法。

Intervertebral disc (IVD) degeneration is the main pathological basis of neck pain and low back pain. Clinical treatment is mainly for "symptoms" rather than "causes". Tissue engineering of nucleus pulposus can promote the regeneration of nucleus pulposus cells, which is expected to achieve the "causes" treatment. However, the effect of microenvironment changes during disc degeneration has not been considered in the existing tissue-engineered nucleus pulposus, resulting in great differences between the experimental results in vivo and in vitro. Many studies had shown that the changes of microenvironment of disc degeneration could inhibit the biological activity of cells. In our previous studies, we found that the inhibition of acid environment is the most significant, and it plays an effect through acid ion sensitive channels (AISCs). Therefore, the key of IVD degeneration treatment is to construct a tissue-engineered nucleus pulposus which can overcome the acid environment. RADA16-I is one kind of polypeptide material which can be self-assembled into hydrogel in vivo. The special peptide can be constructed by inserting special peptide at the C end. Therefore, we designed a new functionalized peptide RAD/SA1 that conjugated the short functional motifs, Sa12b, the inhibitor of AISCs, onto the C-terminus of RADA16-I. Then, the its material characteristics, biocompatibility, the effect and mechanism for nucleus pulposus mesenchymal stem cells in vitro and the effect and mechanism for IVD degeneration in vivo were detected. In addition, another functionalized peptide RAD/SA1/KPS was designed by mixed RAD/SA1 with the peptide RAD / KPS which was conjugated a short functional motif of BMP7 onto the C-terminus of RADA16-I in our precious studies. Then, the synergistic effect of RAD/SA1/KPS on IVD was further observed. This study would not only provide a new concept of the construction of tissue engineering of nucleus pulposus, but also provide a new therapeutic method for IVD degeneration.