Thomas Richelle C, Vu Philip, Modi Shan P, Chung Paul E, Landis R Clive, Khaing Zin Z, Hardy John G, Schmidt Christine E
J. Crayton Pruitt Department of Biomedical Engineering, The University of Florida, Gainesville, Florida 32611, United States.
Department of Chronic Disease Research Centre, Faculty of Medicine, Cave Hill Campus, The University of the West Indies, Wanstead, Barbados.
ACS Biomater Sci Eng. 2017 Jul 10;3(7):1451-1459. doi: 10.1021/acsbiomaterials.7b00002. Epub 2017 May 3.
Pores are key features of natural tissues and the development of tissues scaffolds with biomimetic properties (pore structures and chemical/mechanical properties) offers a route to engineer implantable biomaterials for specific niches in the body. Here we report the use of sacrificial crystals (potassium dihydrogen phosphate or urea) that act as templates to impart pores to hyaluronic acid-based hydrogels. The mechanical properties of the hydrogels were analogous to the nervous system (in the Pascal regime), and we investigated the use of the potassium dihydrogen phosphate crystal-templated hydrogels as scaffolds for neural progenitor cells (NPCs), and the use of urea crystal-templated hydrogels as scaffolds for Schwann cells. For NPCs cultured inside the porous hydrogels, assays for the expression of Nestin are inconclusive, and assays for GFAP and BIII-tubulin expression suggest that the NPCs maintain their undifferentiated phenotype more effectively than the controls (with glial fibrillary acidic protein (GFAP) and BIII-tubulin expression at ca. 50% relative to the chemically/mechanically equivalent not templated control hydrogels). For Schwann cells cultured within these hydrogels, assays for the expression of S100 protein or Myelin basic protein confirm the expression of both proteins, albeit at lower levels on the templated hydrogels (ca. 50%) than on the chemically/mechanically equivalent not templated control hydrogels. Such sacrificial crystal templated hydrogels represent platforms for biomimetic 3D tissue scaffolds for the nervous system.
孔隙是天然组织的关键特征，开发具有仿生特性（孔隙结构以及化学/机械性能）的组织支架为设计用于体内特定微环境的可植入生物材料提供了一条途径。在此，我们报道了使用作为模板的牺牲性晶体（磷酸二氢钾或尿素）来赋予基于透明质酸的水凝胶孔隙。水凝胶的机械性能类似于神经系统（在帕斯卡单位制下），并且我们研究了以磷酸二氢钾晶体为模板的水凝胶作为神经祖细胞（NPCs）支架的用途，以及以尿素晶体为模板的水凝胶作为雪旺细胞支架的用途。对于在多孔水凝胶内部培养的NPCs，巢蛋白表达的检测结果尚无定论，而胶质纤维酸性蛋白（GFAP）和βIII微管蛋白表达的检测表明，与对照组相比，NPCs能更有效地维持其未分化表型（胶质纤维酸性蛋白（GFAP）和βIII微管蛋白的表达相对于化学/机械性能相当的未模板化对照水凝胶约为50%）。对于在这些水凝胶中培养的雪旺细胞，S100蛋白或髓磷脂碱性蛋白表达的检测证实了这两种蛋白的表达，尽管在模板化水凝胶上的表达水平（约50%）低于化学/机械性能相当的未模板化对照水凝胶。这种牺牲性晶体模板化水凝胶代表了用于神经系统的仿生三维组织支架平台。
