Department of Chemical Engineering, McMaster University , 1280 Main Street West, Hamilton, Ontario L8S 4L8, Canada.
Center for Functional Nanomaterials, Brookhaven National Laboratory , Upton, New York 11973, United States.
Nano Lett. 2017 Oct 11;17(10):6487-6495. doi: 10.1021/acs.nanolett.7b03600. Epub 2017 Sep 29.
While injectable in situ cross-linking hydrogels have attracted increasing attention as minimally invasive tissue scaffolds and controlled delivery systems, their inherently disorganized and isotropic network structure limits their utility in engineering oriented biological tissues. Traditional methods to prepare anisotropic hydrogels are not easily translatable to injectable systems given the need for external equipment to direct anisotropic gel fabrication and/or the required use of temperatures or solvents incompatible with biological systems. Herein, we report a new class of injectable nanocomposite hydrogels based on hydrazone cross-linked poly(oligoethylene glycol methacrylate) and magnetically aligned cellulose nanocrystals (CNCs) capable of encapsulating skeletal muscle myoblasts and promoting their differentiation into highly oriented myotubes in situ. CNC alignment occurs on the same time scale as network gelation and remains fixed after the removal of the magnetic field, enabling concurrent CNC orientation and hydrogel injection. The aligned hydrogels show mechanical and swelling profiles that can be rationally modulated by the degree of CNC alignment and can direct myotube alignment both in two- and three-dimensions following coinjection of the myoblasts with the gel precursor components. As such, these hydrogels represent a critical advancement in anisotropic biomimetic scaffolds that can be generated noninvasively in vivo following simple injection.
虽然可注射的原位交联水凝胶作为微创组织支架和控制释放系统引起了越来越多的关注，但它们固有的无组织和各向同性的网络结构限制了它们在工程化生物组织中的应用。鉴于需要外部设备来引导各向异性凝胶的制造和/或需要使用与生物系统不兼容的温度或溶剂，传统的制备各向异性水凝胶的方法不易转化为可注射系统。在此，我们报告了一类新的基于腙交联的聚（低聚乙二醇甲基丙烯酸酯）和通过磁场排列的纤维素纳米晶体（CNC）的可注射纳米复合水凝胶，能够封装骨骼肌成肌细胞并促进其原位分化为高度定向的肌管。CNC 的排列与网络凝胶化同时发生，并且在磁场去除后保持固定，从而能够实现 CNC 取向和水凝胶的同时注射。所制备的各向异性水凝胶具有可通过 CNC 取向程度合理调节的机械和溶胀性能，并能够在与凝胶前体成分共注射的情况下在二维和三维方向上引导肌管的排列。因此，这些水凝胶代表了在各向异性仿生支架方面的重要进展，它们可以通过简单的注射在体内非侵入性地生成。
