Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, United States of America.
Biofabrication. 2017 Jul 5;9(3):034102. doi: 10.1088/1758-5090/aa780f.
Collagen has shown promise as a bioink for extrusion-based bioprinting, but further development of new collagen bioink formulations is necessary to improve their printability. Screening these formulations by measuring print accuracy is a costly and time consuming process. We hypothesized that rheological properties of the bioink before, during, and/or after gelation can be used to predict printability. In this study, we investigated the effects of riboflavin photocrosslinking and pH on type I collagen bioink rheology before, during, and after gelation and directly correlated these findings to the printability of each bioink formulation. From the riboflavin crosslinking study, results showed that riboflavin crosslinking increased the storage moduli of collagen bioinks, but the degree of improvement was less pronounced at higher collagen concentrations. Dots printed with collagen bioinks with riboflavin crosslinking exhibited smaller dot footprint areas than those printed with collagen bioinks without riboflavin crosslinking. From the pH study, results showed that gelation kinetics and final gel moduli were highly pH dependent and both exhibited maxima around pH 8. The shape fidelity of printed lines was highest at pH 8-9.5. The effect of riboflavin crosslinking and pH on cell viability was assessed using bovine chondrocytes. Cell viability in collagen gels was found to decrease after blue light activated riboflavin crosslinking but was not affected by pH. Correlations between rheological parameters and printability showed that the modulus associated with the bioink immediately after extrusion and before deposition was the best predictor of bioink printability. These findings will allow for the more rapid screening of collagen bioink formulations.
胶原蛋白已被证明是挤出式生物打印的生物墨水的良好选择，但需要进一步开发新的胶原蛋白生物墨水配方，以提高其可打印性。通过测量打印精度来筛选这些配方是一个昂贵且耗时的过程。我们假设在凝胶化前后，生物墨水的流变性能可用于预测其可打印性。在这项研究中，我们研究了核黄素光交联和 pH 值对 I 型胶原蛋白生物墨水在凝胶化前后的流变性能的影响，并直接将这些发现与每种生物墨水配方的可打印性相关联。从核黄素交联研究结果来看，核黄素交联增加了胶原蛋白生物墨水的储能模量，但在较高胶原蛋白浓度下，改善程度不太明显。用含有核黄素交联的胶原蛋白生物墨水打印的点的足迹面积小于用不含核黄素交联的胶原蛋白生物墨水打印的点。从 pH 值研究结果来看，凝胶化动力学和最终凝胶模量高度依赖 pH 值，两者均在 pH 值 8 左右达到最大值。打印线条的形状保真度在 pH 值为 8-9.5 时最高。使用牛软骨细胞评估了核黄素交联和 pH 值对细胞活力的影响。发现蓝光激活核黄素交联后胶原蛋白凝胶中的细胞活力下降，但 pH 值不受影响。流变学参数与可打印性之间的相关性表明，挤出后和沉积前与生物墨水相关的模量是生物墨水可打印性的最佳预测指标。这些发现将允许更快速地筛选胶原蛋白生物墨水配方。
