Asadikorayem Maryam, Weber Patrick, Surman František, Puiggalí-Jou Anna, Zenobi-Wong Marcy
Tissue Engineering + Biofabrication Laboratory, Department of Health Sciences and Technology, ETH Zürich, Otto-Stern-Weg 7, Zürich, 8093, Switzerland.
Adv Healthc Mater. 2025 Jan;14(2):e2402890. doi: 10.1002/adhm.202402890. Epub 2024 Nov 5.
Granular hydrogels have recently attracted the attention for diverse tissue engineering applications due to their versatility and modularity. Despite previous studies showing enhanced viability and metabolism of cells encapsulated in these hydrogels, the in vitro immune response and long-term fibrotic response of these scaffolds have not been well characterized. Here, bulk and granular hydrogels are studied based on synthetic zwitterionic (ZI) and natural polysaccharide hyaluronic acid (HA) made with mechanical fragmentation. In vitro, immunomodulatory studies show an increased stimulatory effect of HA granular hydrogels compared to bulk, while both bulk and granular ZI hydrogels do not induce an inflammatory response. Subcutaneous implantation in mice shows that both ZI and HA granular hydrogels resulted in less collagen capsule deposition around implants compared to bulk HA hydrogels 10 weeks after implantation. Moreover, the HA granular hydrogels are infiltrated by host cells, including macrophages and mature blood vessels, in a porosity-dependent manner. However, a large number of cells, including multinucleated giant cells as well as blood vessels, surround bulk and granular ZI hydrogels and are not able to infiltrate. Overall, this study provides new insights on the long-term stability and fibrotic response of granular hydrogels, paving the way for future studies and applications.
颗粒水凝胶因其多功能性和模块化特性，最近在各种组织工程应用中受到关注。尽管先前的研究表明封装在这些水凝胶中的细胞具有更高的活力和代谢能力，但这些支架的体外免疫反应和长期纤维化反应尚未得到充分表征。在此，基于通过机械破碎制备的合成两性离子（ZI）和天然多糖透明质酸（HA），对块状和颗粒状水凝胶进行了研究。在体外，免疫调节研究表明，与块状水凝胶相比，HA颗粒水凝胶具有更强的刺激作用，而块状和颗粒状ZI水凝胶均未引发炎症反应。在小鼠皮下植入实验表明，与植入10周后的块状HA水凝胶相比，ZI和HA颗粒水凝胶在植入物周围导致的胶原胶囊沉积更少。此外，HA颗粒水凝胶以孔隙率依赖的方式被宿主细胞浸润，包括巨噬细胞和成熟血管。然而，大量细胞，包括多核巨细胞以及血管，围绕着块状和颗粒状ZI水凝胶，且无法浸润其中。总体而言，本研究为颗粒水凝胶的长期稳定性和纤维化反应提供了新的见解，为未来的研究和应用铺平了道路。
