Abstract

Hyaluronan-based hydrogels are among the most promising neural tissue engineering materials because of their biocompatibility and the immunomodulation capabilities of their degradation byproducts. Despite these features, the problems related to their handling and mechanical properties have not yet been solved. In the present work it is proposed to address these drawbacks through the development of nanohybrid materials in which different nanometric phases (carbon nanotubes, mesoporous silica nanoparticles) are embedded in a crosslinked hyaluronan matrix. These nanohybrid matrices were next processed in the shape of cylindrical conduits aimed at promoting and improving neural stem cell differentiation and regeneration in neural tracts. These constructs could be of use specifically for peripheral nerve regeneration. Results of the study show that the inclusion of the different phases improved physico-chemical features of the gel such as its relative electrical permittivity, water intake and elastic modulus, giving hints on how the nanometric phase interacts with hyaluronan in the composite as well as for their potential in combined therapeutic approaches. Regarding the in vitro biological behavior of the hybrid tubular scaffolds, an improved early cell adhesion and survival of Schwann cells in their lumen was found, as compared to conduits made of pure hyaluronan gels. Furthermore, the differentiation and survival of neural precursors was not compromised, despite alleged safety concerns.

摘要

基于透明质酸的水凝胶因其生物相容性和降解副产物的免疫调节能力而成为最有前途的神经组织工程材料之一。尽管具有这些特征，但与它们的处理和机械性能相关的问题尚未得到解决。在目前的工作中，建议通过开发纳米混合材料来解决这些缺点，其中不同的纳米相（碳纳米管、介孔二氧化硅纳米粒子）嵌入交联的透明质酸基质中。这些纳米混合基质接下来被加工成圆柱形管道，旨在促进和改善神经束中的神经干细胞分化和再生。这些构建体可专门用于外周神经再生。研究结果表明，不同相的加入改善了凝胶的物理化学特性，例如其相对介电常数、吸水量和弹性模量，提示了纳米相如何与复合材料中的透明质酸相互作用以及它们在联合治疗方法中的潜力。关于通过混合管状支架的体外生物学行为，发现与由纯透明质酸凝胶制成的导管相比，雪旺氏细胞在其管腔中的早期细胞粘附和存活得到改善。此外，尽管存在安全问题，但神经前体的分化和存活并未受到影响。