Wei Xingchen, Liu Yunhai, Liu Jianing, Zhao Zhibo, Cui Jinquan, Sang Derun, Tang Yuzhe, Ding Yijia, Gao Tao, Xue Zhirui, Lv Shilong, Man Zhentao, Li Wei, Li Ningbo
Department of Stomatology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong Province, 250021, PR China.
School of Stomatology, Shandong First Medical University & Shandong Academy of Medical Sciences, Ji'nan, Shandong Province 250117, PR China.
Mater Today Bio. 2025 Aug 5;34:102164. doi: 10.1016/j.mtbio.2025.102164. eCollection 2025 Oct.
Cartilage injury would trigger a chronic inflammatory microenvironment that disrupts tissue regeneration and accelerates the onset of osteoarthritis (OA). However, current treatments primarily focus on the symptomatic relief of OA but fail to address the underlying pathophysiological issues. Herein, we developed an injectable Ca/Sr-crosslinked hydrogel incorporating LGK-974/polydopamine nanoparticles for immune regulation and cartilage regeneration. Given the pivotal role of Wnt signaling activation in OA, LGK-974, a Wnt pathway inhibitor targeting the key upstream component (Porcupine) was first integrated for OA prevention. It came out that Sr optimized the physical properties of the modified hydrogel and synergistically released with LGK-974, which potently suppressed the Wnt/β-catenin pathway, effectively promoted M2 macrophage polarization, reactive oxygen species (ROS) scavenging, chondrocytes proliferation and extracellular matrix (ECM) secretion. studies further confirmed that the hydrogel significantly promoted cartilage repair and stimulated ECM regeneration. Building on the pathogenesis of OA, this study suggests that the novel injectable hydrogel holds great promise as an effective therapeutic strategy for promoting cartilage repair and preventing OA progression through minimally invasive intervention.
软骨损伤会引发慢性炎症微环境，破坏组织再生并加速骨关节炎（OA）的发病。然而，目前的治疗主要集中在OA的症状缓解上，未能解决潜在的病理生理问题。在此，我们开发了一种可注射的钙/锶交联水凝胶，其包含LGK-974/聚多巴胺纳米颗粒，用于免疫调节和软骨再生。鉴于Wnt信号激活在OA中的关键作用，首先整合了靶向关键上游成分（Porcupine）的Wnt通路抑制剂LGK-974用于OA预防。结果表明，锶优化了改性水凝胶的物理性质，并与LGK-974协同释放，其有效抑制了Wnt/β-连环蛋白通路，有效促进了M2巨噬细胞极化、活性氧（ROS）清除、软骨细胞增殖和细胞外基质（ECM）分泌。研究进一步证实，该水凝胶显著促进了软骨修复并刺激了ECM再生。基于OA的发病机制，本研究表明，这种新型可注射水凝胶作为一种有效的治疗策略，通过微创干预促进软骨修复和预防OA进展具有巨大潜力。
