Adaptable Microporous Hydrogels of Propagating NGF-Gradient by Injectable Building Blocks for Accelerated Axonal Outgrowth
Adaptable Microporous Hydrogels of Propagating NGF-Gradient by Injectable Building Blocks for Accelerated Axonal Outgrowth
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DOI：
10.1002/advs.201900520
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发表时间：
2019-07-11
期刊：
影响因子：
15.1
通讯作者：
Hu, Shang-Hsiu
中科院分区：
文献类型：
--
作者：
Hsu, Ru-Siou;Chen, Pei-Yueh;Hu, Shang-Hsiu
再生医学中的可注射水凝胶可以潜在地模仿分层的天然活组织，并通过微创植入手术填充形状复杂的缺损。然而，为了实现这一目标，通常具有无孔结构和不可控制的空间试剂释放的通用水凝胶必须克服组织再生的低细胞穿透率的困难。在这项研究中，一个自适应的微孔水凝胶（AMH）组成的微米级的建筑块与相反的电荷作为一个可注射的矩阵与互连孔和传播梯度生长因子自发组装成一个复杂的形状在真实的时间。通过将梯度浓度的生长因子嵌入构建块中，神经生长因子的传播梯度整合到由神经导管中的构建块构建的细胞穿透性连接孔中，有效地促进细胞迁移并诱导对周围神经缺损的显著桥接作用，在体内4天内实现高达4.7 mm的轴突生长和两倍的轴突纤维强度。这种AMH具有可调的机械性能、生物线索的梯度传播和有效诱导细胞迁移的内在特性，有可能克服水凝胶介导的组织再生的局限性，并有可能用于临床应用。
Injectable hydrogels in regeneration medicine can potentially mimic hierarchical natural living tissue and fill complexly shaped defects with minimally invasive implantation procedures. To achieve this goal, however, the versatile hydrogels that usually possess the nonporous structure and uncontrollable spatial agent release must overcome the difficulties in low cell-penetrative rates of tissue regeneration. In this study, an adaptable microporous hydrogel (AMH) composed of microsized building blocks with opposite charges serves as an injectable matrix with interconnected pores and propagates gradient growth factor for spontaneous assembly into a complex shape in real time. By embedding gradient concentrations of growth factors into the building blocks, the propagated gradient of the nerve growth factor, integrated to the cell-penetrative connected pores constructed by the building blocks in the nerve conduit, effectively promotes cell migration and induces dramatic bridging effects on peripheral nerve defects, achieving axon outgrowth of up to 4.7 mm and twofold axon fiber intensity in 4 days in vivo. Such AMHs with intrinsic properties of tunable mechanical properties, gradient propagation of biocues and effective induction of cell migration are potentially able to overcome the limitations of hydrogel-mediated tissue regeneration in general and can possibly be used in clinical applications.