Asadikorayem Maryam, Weber Patrick, Zhang Shipin, Surman František, Fercher David, Fonti Marina, Bevc Kajetana, Kauppinen Sami, Frondelius Tuomas, Finnilä Mikko A J, Zenobi-Wong Marcy
Tissue Engineering + Biofabrication Laboratory, Department of Health Sciences and Technology, ETH Zürich, Otto-Stern-Weg 7, 8093 Zürich, Switzerland.
Research Unit of Health Sciences and Technology, University of Oulu, Aapistie 5A, 90220 Oulu, Finland.
Biomater Adv. 2025 Apr;169:214151. doi: 10.1016/j.bioadv.2024.214151. Epub 2024 Dec 13.
Osteoarthritis (OA) is one of the most common degenerative joint diseases, with no effective therapeutic options available. In this study, we aimed to develop an interpenetrating, in-situ-forming hydrogel based on biocompatible and anti-fouling zwitterionic (ZI) polymers for early-stage OA treatment. We hypothesized that the anti-fouling properties of zwitterions could provide tissue protection, and the high charge density of these polymers would enhance tissue penetration and lubrication. The hydrogel comprises carboxybetaine acrylamide as the ZI backbone and tyramine acrylamide as a functional comonomer to enable enzymatic and tissue-adhesive crosslinking. The hydrogel demonstrated exceptional tissue penetration and long-term retention in bovine cartilage explants. Moreover, hydrogel application protected cartilage in inflammatory media, enhanced lubrication, and decreased permeability. However, ZI hydrogel injection in collagenase-induced osteoarthritis model in rats did not prevent cartilage degeneration, and similar levels of tissue degradation and surface roughness were observed in rats injected with the ZI hydrogel and in OA controls. Additionally, ZI polymer without in-situ crosslinking resulted in increased cartilage degradation compared to both hydrogel and OA control. Furthermore, synovial tissue inflammation and significantly increased immune cell infiltration were observed in response to ZI materials. This study highlights the potential immunogenicity effect of ZI polymers in our disease model, contributing to impaired protective effects as well as exacerbated degeneration.
骨关节炎（OA）是最常见的退行性关节疾病之一，目前尚无有效的治疗方法。在本研究中，我们旨在开发一种基于生物相容性和抗污两性离子（ZI）聚合物的互穿原位形成水凝胶，用于早期OA治疗。我们假设两性离子的抗污性能可以提供组织保护，并且这些聚合物的高电荷密度将增强组织渗透和润滑。该水凝胶由羧基甜菜碱丙烯酰胺作为ZI主链和酪胺丙烯酰胺作为功能性共聚单体组成，以实现酶促和组织粘附交联。该水凝胶在牛软骨外植体中表现出优异的组织渗透性和长期保留性。此外，水凝胶的应用保护了炎症介质中的软骨，增强了润滑，并降低了渗透性。然而，在大鼠胶原酶诱导的骨关节炎模型中注射ZI水凝胶并不能预防软骨退变，在注射ZI水凝胶的大鼠和OA对照组中观察到相似程度的组织降解和表面粗糙度。此外，与水凝胶和OA对照组相比，未进行原位交联的ZI聚合物导致软骨降解增加。此外，观察到对ZI材料有滑膜组织炎症和明显增加的免疫细胞浸润。本研究强调了ZI聚合物在我们的疾病模型中的潜在免疫原性作用，这导致了保护作用受损以及退变加剧。
