PCFM Lab, GD HPPC Lab, School of Chemistry, Sun Yat-sen University, Guangzhou 510275, China; Guangdong Functional Biomaterials Engineering Technology Research Center, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, China.
Guangdong Peripheral Nerve Tissue Engineering and Technology Research Center, Department of Orthopedic and Microsurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; Department of Orthopedics and Traumatology, Zhujiang Hospital of Southern Medical University, Guangzhou 510280, China.
Mater Sci Eng C Mater Biol Appl. 2021 Jan;120:111791. doi: 10.1016/j.msec.2020.111791. Epub 2020 Dec 10.
The scaffolding biomaterials and their internal structures are crucial in constructing growth-permissive microenvironment for tissue regeneration. A functional bioscaffold not only requires sufficient extracellular matrix components, but also provides topological guidance by mimicry of the ultrastructure of the native tissue. In our laboratory, a decellularized nerve matrix hydrogel derived from porcine sciatic nerve (pDNM-G) is successfully prepared, which shows great promise for peripheral nerve regeneration. Herein, longitudinally oriented microchannel structures were introduced into pDNM-G bioscaffolds (A-pDNM-G) through controlled unidirectional freeze-drying. The axially aligned microchannels effectively directed and significantly promoted neurite extension and Schwann cell migration, assessed by culturing dorsal root ganglion explants on the longitudinal sections of A-pDNM-G scaffolds. Such regenerative cellular responses can be further optimized by tuning the channel sizes. In vivo studies confirmed that the implanted nerve guidance conduits containing A-pDNM-G scaffolds significantly facilitated axonal extension, myelination, and reached considerable functional recovery in 15-mm rat sciatic nerve defects. The incorporation of nerve growth factor further improved the overall performance in the grafted nerve. The bioactive pDNM-G enables controlled release of neurotrophic factor and easy integration of topological cue provided by the axially aligned microchannels into implantable bioscaffolds, which may serve in future clinical treatments of peripheral nerve injury.
支架生物材料及其内部结构对于构建有利于组织再生的生长允许微环境至关重要。功能性生物支架不仅需要足够的细胞外基质成分，还需要通过模拟天然组织的超微结构提供拓扑引导。在我们的实验室中，成功制备了一种源自猪坐骨神经的脱细胞神经基质水凝胶（pDNM-G），它为周围神经再生提供了很大的希望。在此，通过控制单向冷冻干燥将纵向取向的微通道结构引入 pDNM-G 生物支架（A-pDNM-G）中。轴向排列的微通道有效地引导并显著促进了雪旺细胞的迁移和轴突的延伸，通过在 A-pDNM-G 支架的纵截面培养背根神经节外植体来评估。通过调整通道尺寸，可以进一步优化这种再生细胞反应。体内研究证实，含有 A-pDNM-G 支架的植入式神经引导管显著促进了轴突的延伸、髓鞘形成，并在 15mm 大鼠坐骨神经缺损中实现了相当程度的功能恢复。神经生长因子的加入进一步提高了移植神经的整体性能。具有生物活性的 pDNM-G 能够控制神经营养因子的释放，并将轴向排列的微通道提供的拓扑线索轻松整合到可植入的生物支架中，这可能有助于未来周围神经损伤的临床治疗。
