Additive manufacturing has shown promising results in reconstructing three-dimensional (3D) living tissues for various applications, including tissue engineering, regenerative medicine, drug discovery, and high-throughput drug screening. In extrusion-based bioprinters, stable formation of filaments and high-fidelity deposition of bioinks are the primary challenges in fabrication of physiologically relevant tissue constructs. Among various bioinks, gelatin methacryloyl (GelMA) is known as a photocurable and physicochemically tunable hydrogel with a demonstrated biocompatibility and tunable biodegradation properties. The two-step crosslinking of GelMA (reversible thermal gelation and permanent photo-crosslinking) has attracted researchers to make complex tissue constructs. Despite promising results in filament formation and printability of this hydrogel, the effect of temperature on physicochemical properties, cytocompatibility, and biodegradation of the hydrogel are to be investigated. This work studies the effect of thermoreversible, physical crosslinking on printability of GelMA. The results of 3D printing of GelMA at different temperatures followed by irreversible chemical photo-crosslinking show that the decrease in temperature improves the filament formation and shape fidelity of the deposited hydrogel, particularly at the temperatures around 15 C. Time dependant mechanical testing of the printed samples revealed that decreasing the extruding temperature increases the elastic properties of the extruded filaments. Furthermore, our novel approach in minimizing the slippage effect during rheological study enabled to measure changes in linear and non-linear viscoelastic properties of the printed samples at different temperatures. A considerable increase in storage modulus of the extruded samples printed at lower temperatures confirms their higher solid behavior. Scanning electron microscopy revealed a remarkable decrease in porosity of the extruded hydrogels by decreasing the temperature. Chemical analysis by Fourier-transform infrared spectroscopy and circular dichroism showed a direct relationship between the coil-helix transition in hydrogel macromers and its physical alterations. Finally, biodegradation and cytocompatibility of the extruded hydrogels decreased at lower extruding temperatures.

增材制造在为各种应用重建三维 (3D) 活组织方面显示出可喜的成果，包括组织工程、再生医学、药物发现和高通量药物筛选。在基于挤压的生物打印机中，细丝的稳定形成和生物墨水的高保真沉积是制造生理相关组织结构的主要挑战。在各种生物墨水中，明胶甲基丙烯酰 (GelMA) 被称为光固化和物理化学可调的水凝胶，具有已证明的生物相容性和可调的生物降解特性。GelMA 的两步交联（可逆热凝胶化和永久光交联）吸引了研究人员制作复杂的组织结构。尽管这种水凝胶在细丝形成和可打印性方面取得了令人鼓舞的结果，但温度对水凝胶的理化性质、细胞相容性和生物降解的影响仍有待研究。这项工作研究了热可逆物理交联对 GelMA 可印刷性的影响。GelMA 在不同温度下的 3D 打印结果以及不可逆的化学光交联表明，温度的降低改善了沉积水凝胶的细丝形成和形状保真度，特别是在 15 C 左右的温度下。打印的时间依赖性机械测试样品表明，降低挤出温度会增加挤出长丝的弹性。此外，我们在流变学研究中最大限度地减少滑移效应的新方法能够测量印刷样品在不同温度下的线性和非线性粘弹性特性的变化。在较低温度下印刷的挤出样品的储能模量显着增加证实了它们更高的固体性能。扫描电子显微镜显示，通过降低温度，挤出水凝胶的孔隙率显着降低。通过傅里叶变换红外光谱和圆二色性进行的化学分析表明，水凝胶大分子单体中的螺旋-螺旋转变与其物理变化之间存在直接关系。最后，挤出水凝胶的生物降解和细胞相容性在较低的挤出温度下降低。