Department of Chemical Engineering, Neyshabur Branch, Islamic Azad University, Neyshabur, Iran.
Department of Chemistry, Faculty of Sciences, Neyshabur Branch, Islamic Azad University, Neyshabur, Iran; Avdanced Research Center of Chemistry Biochemistry & Nanomaterial, Neyshabur Branch, Islamic Azad University, Neyshabur, Iran.
Int J Biol Macromol. 2022 Jun 30;211:700-710. doi: 10.1016/j.ijbiomac.2022.05.080. Epub 2022 May 16.
Cell-laden filament-like hydrogels are advantageous for many applications including drug screening, tissue engineering, and regenerative medicine. However, most of the designed filament vehicles hold weak mechanical properties, which hinder their applications in specific tissue engineering. We present a binary hybrid silk and hyaluronic acid hydrogel microfiber generated through a microfluidic system to encapsulate cells with superior mechanical properties and biocompatibility. Cell-laden hydrogel microfibers were continuously produced through coaxial double orifice microfluidic device and horseradish peroxidase mediated crosslinking, which conjugated introduce phenolic moieties in the backbone of silk fibroin and HA derivatives (Silk-Ph and HA-Ph, respectively). The iterative hybrid Silk-Ph + HA-Ph fibers were fabricated in tunable size distribution between 195 and 680 μm through control of outer flow velocity. Tensile strength and maximum stain of prepared Silk-Ph + HA-Ph sample upregulated more than three times higher than the single HA-Ph sample, which demonstrated significant impacts of synthesized silk derivative in hydrogel fiber composition. The proteolytic degradation of microfibers manipulated by hyaluronidase and collagenase treatment. Encapsulation process and crosslinking did not insert any harmful effect on cell viability (> 90%) and the cells maintained their growth ability after encapsulation process. Cellular filament-like tissue fabricated from proliferation of cells in Silk-Ph + HA-Ph microfiber.
细胞填充的纤维状水凝胶在许多应用中具有优势，包括药物筛选、组织工程和再生医学。然而，大多数设计的纤维载体具有较弱的机械性能，这限制了它们在特定组织工程中的应用。我们通过微流控系统展示了一种二元混合丝素和透明质酸水凝胶微纤维，用于封装具有优异机械性能和生物相容性的细胞。通过同轴双孔微流控装置和辣根过氧化物酶介导的交联，连续产生细胞填充水凝胶微纤维，该交联在丝素和透明质酸衍生物（分别为 Silk-Ph 和 HA-Ph）的主链中引入酚基。通过控制外流速，可以在 195 至 680 μm 之间的可调尺寸分布中制造迭代混合 Silk-Ph + HA-Ph 纤维。与单一的 HA-Ph 样品相比，制备的 Silk-Ph + HA-Ph 样品的拉伸强度和最大应变提高了三倍以上，这表明合成丝素衍生物对水凝胶纤维组成有显著影响。通过透明质酸酶和胶原酶处理来控制微纤维的蛋白水解降解。包封过程和交联对细胞活力（>90%）没有任何有害影响，并且细胞在包封过程后保持其生长能力。细胞在 Silk-Ph + HA-Ph 微纤维中增殖，形成类似细胞的纤维状组织。
