Huber Birgit, Hoch Eva, Calderon Iván, Borchers Kirsten, Kluger Petra J
University of Stuttgart, Institute of Interfacial Process Engineering and Plasma Technology, Stuttgart, Germany.
Unitechnologies SA, Gals, Switzerland.
Biomed Tech (Berl). 2019 Aug 27;64(4):397-406. doi: 10.1515/bmt-2018-0015.
Size and function of bioartificial tissue models are still limited due to the lack of blood vessels and dynamic perfusion for nutrient supply. In this study, we evaluated the use of cytocompatible methacryl-modified gelatin for the fabrication of a hydrogel-based tube by dip-coating and subsequent photo-initiated cross-linking. The wall thickness of the tubes and the diameter were tuned by the degree of gelatin methacryl-modification and the number of dipping cycles. The dipping temperature of the gelatin solution was adjusted to achieve low viscous fluids of approximately 0.1 Pa s and was different for gelatin derivatives with different modification degrees. A versatile perfusion bioreactor for the supply of surrounding tissue models was developed, which can be adapted to several geometries and sizes of blood-vessel mimicking tubes. The manufactured bendable gelatin tubes were permeable for water and dissolved substances, like Nile Blue and serum albumin. As a proof of concept, human fibroblasts in a three-dimensional collagen tissue model were successfully supplied with nutrients via the central gelatin tube under dynamic conditions for 2 days. Moreover, the tubes could be used as scaffolds to build-up a functional and viable endothelial layer. Hence, the presented tools can contribute to solving current challenges in tissue engineering.
由于缺乏血管以及用于营养供应的动态灌注，生物人工组织模型的尺寸和功能仍然有限。在本研究中，我们评估了使用细胞相容性甲基丙烯酸改性明胶通过浸涂和随后的光引发交联来制造水凝胶基管。通过明胶甲基丙烯酸改性程度和浸涂循环次数来调节管的壁厚和直径。调节明胶溶液的浸涂温度以获得约0.1 Pa·s的低粘性流体，对于不同改性程度的明胶衍生物，浸涂温度有所不同。开发了一种用于为周围组织模型供应营养的通用灌注生物反应器，它可以适应多种几何形状和尺寸的血管模拟管。制造的可弯曲明胶管对水和溶解物质（如尼罗蓝和血清白蛋白）具有渗透性。作为概念验证，在动态条件下，通过中央明胶管成功地为三维胶原组织模型中的人成纤维细胞供应营养2天。此外，这些管可用作支架来构建功能性且有活力的内皮细胞层。因此，所展示的工具有助于解决组织工程中的当前挑战。
