Centre for Translational Medicine Research & Development, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, P. R. China.
University of Chinese Academy of Sciences, Shenzhen, Guangdong 518055, P. R. China.
J Mater Chem B. 2022 Jun 8;10(22):4242-4253. doi: 10.1039/d2tb00548d.
Producing a bioink that fulfills the physicochemical requirements of printing and provides a desirable environment for encapsulated cells is a major challenge in three-dimensional (3D) bioprinting. Thus, we have developed a biocompatible bioink (ECM@MeHA bioink) with suitable mechanical support and visible light printable properties. In this bioink system, the thermosensitive extracellular matrix (ECM) was prepared and can be crosslinked at 37 °C. And the prepared methacrylated hyaluronic acid (MeHA) can be crosslinked under visible light using the biosafe initiators (Eosin Y, TEOA, and NVP). Thus, the ECM@MeHA bioink consisted of a mix solution of ECM and MeHA containing visible light initiators can cure at 515 nm visible light for 30 s and then further crosslinked at 37 °C to form a double network hydrogel. Then, the mechanical properties and biocompatibility of ECM@MeHA hydrogel, and the printability and the cell viability of the ECM@MeHA bioink were systemically evaluated. The results showed that the mechanical property of the MeHA hydrogel is significantly improved following the addition of 10 mg mL of ECM (10ECM@MeHA). The compressive strength and modulus of 10ECM@MeHA hydrogel were 102.38 ± 5.27 kPa and 782 ± 20.36 kPa, which were 2.7 times and 3.1 times higher than those of MeHA, respectively. After encapsulating MC3T3-E1 cells in the 10ECM@MeHA hydrogel for 7 days, the culture showed excellent biocompatibility. The 10ECM@MeHA bioink and cell-laden 10ECM@MeHA bioink were printed, and the cells were successfully encapsulated by the extrusion-based bioprinting and digital light processing (DLP) -based bioprinting. The cell-laden 10ECM@MeHA scaffold showed 94.27 ± 3.00% cell viability after 7 days of the 3D culture. In conclusion, 10ECM@MeHA bioink may provide a new strategy for constructing disease models or drug screening models and is expected to be widely used in the field of tissue engineering scaffolds.
在三维（3D）生物打印中，生产满足打印要求的理化性质并为包封细胞提供理想环境的生物墨水是一个主要挑战。因此，我们开发了一种具有合适机械支撑和可见光照印性质的生物相容性生物墨水（ECM@MeHA 生物墨水）。在该生物墨水体系中，制备了热敏细胞外基质（ECM），并可以在 37°C 下交联。并且，所制备的甲基丙烯酰化透明质酸（MeHA）可以使用生物安全引发剂（曙红 Y、TEOA 和 NVP）在可见光下交联。因此，ECM@MeHA 生物墨水由包含可见光引发剂的 ECM 和 MeHA 的混合溶液组成，可在 515nm 可见光下照射 30s 进行固化，然后在 37°C 下进一步交联形成双网络水凝胶。然后，系统地评估了 ECM@MeHA 水凝胶的机械性能和生物相容性，以及 ECM@MeHA 生物墨水的可打印性和细胞活力。结果表明，添加 10mg/mL ECM（10ECM@MeHA）可显著提高 MeHA 水凝胶的机械性能。10ECM@MeHA 水凝胶的压缩强度和模量分别为 102.38±5.27kPa 和 782±20.36kPa，分别是 MeHA 的 2.7 倍和 3.1 倍。将 MC3T3-E1 细胞包封在 10ECM@MeHA 水凝胶中培养 7 天后，显示出优异的生物相容性。通过挤出式生物打印和数字光处理（DLP）式生物打印打印了 10ECM@MeHA 生物墨水和细胞负载的 10ECM@MeHA 生物墨水，并成功地通过挤出式生物打印和数字光处理（DLP）式生物打印将细胞包封在其中。细胞负载的 10ECM@MeHA 支架在 3D 培养 7 天后的细胞活力为 94.27±3.00%。总之，10ECM@MeHA 生物墨水可为构建疾病模型或药物筛选模型提供新策略，并有望在组织工程支架领域得到广泛应用。
