Osteoarthritis (OA) of the knee joint is a degenerative disease initiated by mechanical stress that affects millions of individuals. The disease manifests as joint damage and synovial inflammation. Post-traumatic osteoarthritis (PTOA) is a specific form of OA caused by mechanical trauma to the joint. The progression of PTOA is prevented by immediate post-injury therapeutic intervention. Intra-articular injection of anti-inflammatory therapeutics (e.g. corticosteroids) is a common treatment option for OA before end-stage surgical intervention. However, the efficacy of intra-articular injection is limited due to poor drug retention time in the joint space and the variable efficacy of corticosteroids. Here, we endeavored to characterize a four-arm maleimide-functionalized polyethylene glycol (PEG-4MAL) hydrogel system as a 'mechanical pillow' to cushion the load-bearing joint, withstand repetitive loading and improve the efficacy of intra-articular injections of nanoparticles containing dexamethasone, an anti-inflammatory agent. PEG-4MAL hydrogels maintained their mechanical properties after physiologically relevant cyclic compression and released therapeutic payload in an on-demand manner under in vitro inflammatory conditions. Importantly, the on-demand hydrogels did not release nanoparticles under repetitive mechanical loading as experienced by daily walking. Although dexamethasone had minimal protective effects on OA-like pathology in our studies, the PEG-4MAL hydrogel functioned as a mechanical pillow to protect the knee joint from cartilage degradation and inhibit osteophyte formation in an in vivo load-induced OA mouse model.

中文翻译：

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可注射机械枕头，用于减轻负荷引起的创伤后骨关节炎。

膝关节骨关节炎 (OA) 是一种由机械应力引发的退行性疾病，影响数百万人。该病表现为关节损伤和滑膜炎症。创伤后骨关节炎 (PTOA) 是由关节机械创伤引起的 OA 的一种特殊形式。损伤后立即进行治疗干预可防止 PTOA 的进展。关节内注射抗炎治疗药物（例如皮质类固醇）是终末期手术干预前 OA 的常见治疗选择。然而，由于药物在关节间隙的保留时间差以及皮质类固醇的疗效不稳定，关节内注射的疗效受到限制。在这里，我们努力将四臂马来酰亚胺功能化聚乙二醇（PEG-4MAL）水凝胶系统描述为“机械枕头”，以缓冲承重关节，承受重复负载并提高关节内注射纳米颗粒的功效含有地塞米松，一种抗炎剂。PEG-4MAL 水凝胶在生理相关的循环压缩后保持其机械性能，并在体外炎症条件下按需释放治疗有效负载。重要的是，按需水凝胶在日常行走所经历的重复机械负荷下不会释放纳米颗粒。尽管在我们的研究中地塞米松对 OA 样病理学具有最小的保护作用，但 PEG-4MAL 水凝胶可作为机械枕头，在体内负荷诱导的 OA 小鼠模型中保护膝关节免遭软骨降解并抑制骨赘形成。