Ben Messaoud Ghazi, Aveic Sanja, Wachendoerfer Mattis, Fischer Horst, Richtering Walter
Institute of Physical Chemistry, RWTH Aachen University, Landoltweg 2, European Union, 52074, Aachen, Germany.
DWI-Leibniz Institute for Interactive Materials, Forckenbeckstrasse 50, European Union, 52074, Aachen, Germany.
Small. 2023 Nov;19(44):e2208089. doi: 10.1002/smll.202208089. Epub 2023 Jul 4.
The restricted porosity of most hydrogels established for in vitro 3D tissue engineering applications limits embedded cells with regard to their physiological spreading, proliferation, and migration behavior. To overcome these confines, porous hydrogels derived from aqueous two-phase systems (ATPS) are an interesting alternative. However, while developing hydrogels with trapped pores is widespread, the design of bicontinuous hydrogels is still challenging. Herein, an ATPS consisting of photo-crosslinkable gelatin methacryloyl (GelMA) and dextran is presented. The phase behavior, monophasic or biphasic, is tuned via the pH and dextran concentration. This, in turn, allows the formation of hydrogels with three distinct microstructures: homogenous nonporous, regular disconnected-pores, and bicontinuous with interconnected-pores. The pore size of the latter two hydrogels can be tuned from ≈4 to 100 µm. Cytocompatibility of the generated ATPS hydrogels is confirmed by testing the viability of stromal and tumor cells. Their distribution and growth pattern are cell-type specific but are also strongly defined by the microstructure of the hydrogel. Finally, it is demonstrated that the unique porous structure is sustained when processing the bicontinuous system by inkjet and microextrusion techniques. The proposed ATPS hydrogels hold great potential for 3D tissue engineering applications due to their unique tunable interconnected porosity.
大多数为体外三维组织工程应用而制备的水凝胶孔隙受限，这在生理铺展、增殖和迁移行为方面限制了包埋细胞。为克服这些限制，源自双水相体系（ATPS）的多孔水凝胶是一种有趣的替代方案。然而，虽然开发具有截留孔隙的水凝胶很普遍，但双连续水凝胶的设计仍然具有挑战性。在此，提出了一种由光可交联甲基丙烯酰化明胶（GelMA）和葡聚糖组成的ATPS。通过pH值和葡聚糖浓度调节其单相或双相的相行为。这进而允许形成具有三种不同微观结构的水凝胶：均匀无孔、规则不连通孔以及具有相互连通孔的双连续结构。后两种水凝胶的孔径可在约4至100微米范围内调节。通过测试基质细胞和肿瘤细胞的活力，证实了所生成的ATPS水凝胶的细胞相容性。它们的分布和生长模式具有细胞类型特异性，但也强烈地由水凝胶的微观结构决定。最后，证明了通过喷墨和微挤压技术处理双连续体系时，独特的多孔结构得以维持。所提出的ATPS水凝胶因其独特的可调相互连通孔隙率在三维组织工程应用中具有巨大潜力。
