Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), 291 University Road, Yuseong-gu, Daejeon 34141, South Korea; Department of Bioengineering, University of Pennsylvania, 210 South 33rd Street, Philadelphia, PA 19104, USA.
Department of Bioengineering, University of Pennsylvania, 210 South 33rd Street, Philadelphia, PA 19104, USA.
Acta Biomater. 2019 Sep 1;95:165-175. doi: 10.1016/j.actbio.2018.10.028. Epub 2018 Oct 24.
3D bioprinting is an attractive technique to fabricate well-organized, cell-laden constructs for tissue repair and disease modeling. Although numerous hydrogel bioinks have been developed, materials are still needed that mimic the cellular microenvironment, have the appropriate viscosity and stabilization for printing, and are cytocompatible. Here, we present a unique gallol-modified extracellular matrix (ECM) hydrogel ink that is inspired by rapid fruit browning phenomena. The gallol-modification of ECM components (e.g., hyaluronic acid, gelatin) allowed (i) immediate gelation and shear-thinning properties by dynamic hydrogen bonds on short time-scales and (ii) further auto-oxidation and covalent crosslinking for stabilization on longer time-scales. The gallol ECM hydrogel ink was printable using an extrusion-based 3D printer by exploiting temporal shear-thinning properties, and further showed cytocompatibility (∼95% viability) and on-tissue printability due to adhesiveness of gallol moieties. Printed cell-laden filaments degraded and swelled with culture over 6 days, corresponding to increases in cell density and spreading. Ultimately, this strategy is useful for designing hydrogel inks with tunable properties for 3D bioprinting. STATEMENT OF SIGNIFICANCE: 3D bioprinting is a promising technique for the fabrication of cell-laden constructs for applications as in vitro models or for therapeutic applications. Despite the previous development of numerous hydrogel bioinks, there still remain challenging considerations in the design of bioinks. In this study, we present a unique cytocompatible hydrogel ink with gallol modification that is inspired by rapid fruit browning phenomena. The gallol hydrogel ink has three important properties: i) it shows immediate gelation by dynamic, reversible bonds for shear-thinning extrusion, ii) it allows spontaneous stabilization by subsequent covalent crosslinking after printing, and iii) it is printable on tissues by adhesive properties of gallol moieties. As such, this work presents a new approach in the design of hydrogel inks.
3D 生物打印是一种有吸引力的技术，可以制造组织修复和疾病建模的组织有序、细胞负载的构建体。尽管已经开发了许多水凝胶生物墨水，但仍需要模拟细胞微环境的材料，具有适当的粘度和打印稳定性，并且细胞相容。在这里，我们提出了一种独特的多酚修饰细胞外基质（ECM）水凝胶墨水，灵感来自于快速的水果褐变现象。ECM 成分（如透明质酸、明胶）的多酚修饰允许（i）通过短时间尺度上的动态氢键立即凝胶化和剪切稀化特性，（ii）通过进一步的自动氧化和共价交联在较长时间尺度上进行稳定化。多酚 ECM 水凝胶墨水可通过利用时间剪切稀化特性使用基于挤出的 3D 打印机进行打印，并且由于多酚部分的粘附性，进一步显示出细胞相容性（约 95%活力）和组织内打印性。由于培养时间超过 6 天，细胞负载的纤维降解和肿胀，对应于细胞密度和扩散的增加。最终，该策略对于设计具有可调节 3D 生物打印特性的水凝胶墨水是有用的。
3D 生物打印是一种有前途的技术，用于制造细胞负载的构建体，可用于体外模型或治疗应用。尽管之前已经开发了许多水凝胶生物墨水，但在生物墨水的设计中仍然存在具有挑战性的考虑因素。在这项研究中，我们提出了一种独特的多酚修饰细胞相容水凝胶墨水，灵感来自于快速的水果褐变现象。多酚水凝胶墨水具有三个重要特性：i）它通过动态、可逆键立即凝胶化，以进行剪切稀化挤出，ii）它允许在打印后通过随后的共价交联进行自发稳定化，iii）它通过多酚部分的粘附性在组织上进行打印。因此，这项工作提出了水凝胶墨水设计的新方法。
