Zhang Deteng, Li Ziming, Shi Haifei, Yao Yuejun, Du Wang, Lu Pan, Liang Kejiong, Hong Liangjie, Gao Changyou
MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China.
Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou, 310058, China.
Bioact Mater. 2021 Jul 15;9:134-146. doi: 10.1016/j.bioactmat.2021.07.010. eCollection 2022 Mar.
Both of the surface topographical features and distribution of biochemical cues can influence the cell-substrate interactions and thereby tissue regeneration . However, they have not been combined simultaneously onto a biodegradable scaffold to demonstrate the synergistic role so far. In this study, a proof-of-concept study is performed to prepare micropatterns and peptide gradient on the inner wall of a poly (D,L-lactide--caprolactone) (PLCL) guidance conduit and its advantages in regeneration of peripheral nerve . After linear ridges/grooves of 20/40 μm in width are created on the PLCL film, its surface is aminolyzed in a kinetically controlled manner to obtain the continuous gradient of amino groups, which are then transferred to CQAASIKVAV peptide density gradient via covalent coupling of glutaraldehyde. The Schwann cells are better aligned along with the stripes, and show a faster migration rate toward the region of higher peptide density. Implantation of the nerve guidance conduit made of the PLCL film having both the micropatterns and peptide gradient can significantly accelerate the regeneration of sciatic nerve in terms of rate, function recovery and microstructures, and reduction of fibrosis in muscle tissues. Moreover, this nerve conduit can also benefit the M2 polarization of macrophages and promote vascularization .
表面形貌特征和生化信号的分布均可影响细胞与基质的相互作用,进而影响组织再生。然而,到目前为止,它们尚未同时结合到可生物降解支架上以证明其协同作用。在本研究中,进行了一项概念验证研究,以在聚(D,L-丙交酯-己内酯)(PLCL)引导导管的内壁上制备微图案和肽梯度,并研究其在周围神经再生中的优势。在PLCL膜上制作宽度为20/40μm的线性脊/槽后,以动力学控制的方式对其表面进行氨解,以获得连续的氨基梯度,然后通过戊二醛的共价偶联将其转化为CQAASIKVAV肽密度梯度。雪旺细胞更好地沿着条纹排列,并向肽密度较高的区域显示出更快的迁移速率。植入具有微图案和肽梯度的PLCL膜制成的神经引导导管,在速率、功能恢复和微观结构方面可显著加速坐骨神经的再生,并减少肌肉组织中的纤维化。此外,这种神经导管还可促进巨噬细胞的M2极化并促进血管生成。