Schulik Jana, Salehi Sahar, Boccaccini Aldo R, Schrüfer Stefan, Schubert Dirk W, Arkudas Andreas, Kengelbach-Weigand Annika, Horch Raymund E, Schmid Rafael
Laboratory for Tissue-Engineering and Regenerative Medicine, Department of Plastic and Hand Surgery University Hospital of Erlangen, Krankenhausstraße 12, 91054 Erlangen, Germany.
Chair of Biomaterials, University of Bayreuth, Prof.-Rüdiger-Bormann-Str. 1, 95447 Bayreuth, Germany.
Bioengineering (Basel). 2023 Jun 23;10(7):751. doi: 10.3390/bioengineering10070751.
Biomaterials with characteristics similar to extracellular matrix and with suitable bioprinting properties are essential for vascular tissue engineering. In search for suitable biomaterials, this study investigated the three hydrogels alginate/hyaluronic acid/gelatin (Alg/HA/Gel), pre-crosslinked alginate di-aldehyde with gelatin (ADA-GEL), and gelatin methacryloyl (GelMA) with respect to their mechanical properties and to the survival, migration, and proliferation of human umbilical vein endothelial cells (HUVECs). In addition, the behavior of HUVECs was compared with their behavior in Matrigel. For this purpose, HUVECs were mixed with the inks both as single cells and as cell spheroids and printed using extrusion-based bioprinting. Good printability with shape fidelity was determined for all inks. The rheological measurements demonstrated the gelling consistency of the inks and shear-thinning behavior. Different Young's moduli of the hydrogels were determined. However, all measured values where within the range defined in the literature, leading to migration and sprouting, as well as reconciling migration with adhesion. Cell survival and proliferation in ADA-GEL and GelMA hydrogels were demonstrated for 14 days. In the Alg/HA/Gel bioink, cell death occurred within 7 days for single cells. Sprouting and migration of the HUVEC spheroids were observed in ADA-GEL and GelMA. Similar behavior of the spheroids was seen in Matrigel. In contrast, the spheroids in the Alg/HA/Gel ink died over the time studied. It has been shown that Alg/HA/Gel does not provide a good environment for long-term survival of HUVECs. In conclusion, ADA-GEL and GelMA are promising inks for vascular tissue engineering.
具有与细胞外基质相似特性且具备合适生物打印性能的生物材料对于血管组织工程至关重要。为了寻找合适的生物材料，本研究考察了三种水凝胶：海藻酸盐/透明质酸/明胶（Alg/HA/Gel）、预交联的二醛海藻酸盐与明胶（ADA-GEL）以及甲基丙烯酰化明胶（GelMA），研究了它们的力学性能以及对人脐静脉内皮细胞（HUVECs）存活、迁移和增殖的影响。此外，还将HUVECs的行为与它们在基质胶中的行为进行了比较。为此，将HUVECs以单细胞和细胞球状体的形式与墨水混合，并使用基于挤出的生物打印技术进行打印。所有墨水均具有良好的形状保真度可打印性。流变学测量表明了墨水的凝胶化稠度和剪切变稀行为。测定了水凝胶不同的杨氏模量。然而，所有测量值都在文献定义的范围内，从而导致迁移和发芽，并使迁移与粘附相协调。ADA-GEL和GelMA水凝胶中的细胞存活和增殖在14天内得到了证实。在Alg/HA/Gel生物墨水中，单细胞在7天内发生细胞死亡。在ADA-GEL和GelMA中观察到了HUVEC细胞球状体的发芽和迁移。在基质胶中也观察到了细胞球状体的类似行为。相比之下，Alg/HA/Gel墨水中的细胞球状体在研究期间死亡。结果表明，Alg/HA/Gel不能为HUVECs的长期存活提供良好的环境。总之，ADA-GEL和GelMA是血管组织工程中有前景的墨水。
