Cixi Institute of Biomedical Engineering, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, China.
University of Chinese Academy of Science, No. 19 (A) Yuquan Road, Shijingshan District, Beijing 100049, China.
ACS Appl Mater Interfaces. 2021 May 19;13(19):22902-22913. doi: 10.1021/acsami.1c01321. Epub 2021 May 7.
Biomimetic constructs imitating the functions, structures, and compositions of normal tissues are of great importance for tissue repair and regeneration. Three-dimensional (3D) printing is an innovative method to construct intricate biomimetic 3D tissue engineering scaffolds with spatiotemporal deposition of materials to control the intrinsic architectural organization and functional performance of the scaffold. However, due to the lack of bioinks with suitable printability, high structural integrity, and biological compatibility, producing constructs that mimic the anisotropic 3D extracellular environments remains a challenge. Here, we present a printable hydrogel ink based on methylacrylate-modified chitosan (ChMA) and gelatin (GelMA) embedding nanohydroxyapatite (nano-Hap). This polymer composite is first physically cross-linked by thermal gelation for postprinting structural stability, followed by covalent photo-cross-linking of ChMA and GelMA to form a long-term stable structure. The rheological behavior of the hydrogels and the mechanical strengths of the printed constructs are tuned by adjusting the content of GelMA, which in turn enhances the shape retention after printing and enables the precise deposition of multilayered 3D scaffolds. Moreover, the formulated biomaterial inks exhibit biological characteristics that effectively support the spreading and proliferation of stem cells seeded on the scaffolds after 7 days of in vitro culture. Adding Hap has minor influences on the mechanical rigidity and cytocompatibility of the hydrogels compared with the group free of Hap. Together, the printable biomaterial inks with shear thinning and good structural integrity, along with biological cues, are promising for tissue engineering application.
仿生结构模仿正常组织的功能、结构和组成对于组织修复和再生非常重要。三维（3D）打印是一种创新的方法，可以构建具有时空材料沉积的复杂仿生 3D 组织工程支架，以控制支架的固有结构组织和功能性能。然而，由于缺乏具有适当可打印性、高结构完整性和生物相容性的生物墨水，制造模仿各向异性 3D 细胞外环境的构建体仍然是一个挑战。在这里，我们提出了一种基于甲基丙烯酰改性壳聚糖（ChMA）和明胶（GelMA）嵌入纳米羟基磷灰石（nano-Hap）的可打印水凝胶墨水。该聚合物复合材料首先通过热凝胶化进行物理交联，以获得后打印结构稳定性，然后通过 ChMA 和 GelMA 的共价光交联形成长期稳定的结构。通过调整 GelMA 的含量来调节水凝胶的流变行为和打印结构的机械强度，这反过来又增强了打印后的形状保持能力，并实现了多层 3D 支架的精确沉积。此外，所制定的生物材料墨水表现出生物特性，有效地支持在体外培养 7 天后接种在支架上的干细胞的扩散和增殖。与不含 Hap 的组相比，Hap 的添加对水凝胶的机械刚性和细胞相容性的影响较小。具有剪切变稀和良好结构完整性以及生物线索的可打印生物材料墨水有望用于组织工程应用。
