Osteoarthritis (OA) is one of the most common chronic musculoskeletal diseases, which accounts for a large proportion of physical disabilities worldwide. Herein, we fabricated injectable gelatin/poly(L-lactide)-based nanofibrous microspheres (MS) via electrospraying technology, which were further modified with tannic acid (TA) named as TMS or metal phenolic networks (MPNs) consisting of TA and strontium ions (Sr²⁺) and named as TSMS to enhance their bioactivity for OA therapy. The TA-modified microspheres exhibited stable porous structure and anti-oxidative activity. Notably, TSMS showed a sustained release of TA as compared to TMS, which exhibited a burst release of TA. While all types of microspheres exhibited good cytocompatibility, TSMS displayed good anti-inflammatory properties with higher cell viability and cartilage-related extracellular matrix (ECM) secretion. The TSMS microspheres also showed less apoptosis of chondrocytes in the hydrogen peroxide (H₂O₂)-induced inflammatory environment. The TSMS also inhibited the degradation of cartilage along with the considerable repair outcome in the papain-induced OA rabbit model in vivo as well as suppressed the expression level of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1-beta (IL-1β). Taken together, TSMS may provide a highly desirable therapeutic option for intra-articular treatment of OA.

Statement of significance

Osteoarthritis (OA) is a chronic disease, which is caused by the inflammation of joint. Current treatments for OA achieve pain relief but hardly prevent or slow down the disease progression. Microspheres are at the forefront of drug delivery and tissue engineering applications, which can also be minimal-invasively injected into the joint. Polyphenols and therapeutic ions have been shown to be beneficial for the treatment of diseases related to the joints, including OA. Herein, we prepared gelatin/poly(L-lactide)-based nanofibrous microspheres (MS) via electrospinning incorporated electrospraying technology and functionalized them with the metal phenolic networks (MPNs) consisting of TA and strontium ions (Sr²⁺), and assessed their potential for OA therapy both in vitro and in vivo.

中文翻译：

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用金属酚网络修饰的可注射纳米纤维微球用于有效治疗骨关节炎

骨关节炎（OA）是最常见的慢性肌肉骨骼疾病之一，占全球身体残疾的很大比例。在此，我们通过电喷雾技术制备了可注射明胶/聚（L-丙交酯）基纳米纤维微球（MS），并用称为 TMS 的单宁酸（TA）或由 TA 和锶离子组成的金属酚网络（MPN）进一步改性（高级²⁺) 并命名为 TSMS 以增强其对 OA 治疗的生物活性。TA 修饰的微球表现出稳定的多孔结构和抗氧化活性。值得注意的是，与 TMS 相比，TSMS 显示了 TA 的持续释放，TMS 展示了 TA 的爆发释放。虽然所有类型的微球都表现出良好的细胞相容性，但 TSMS 显示出良好的抗炎特性，具有更高的细胞活力和软骨相关的细胞外基质 (ECM) 分泌。TSMS 微球还显示在过氧化氢 (H ₂ O ₂ ) 诱导的炎症环境中软骨细胞凋亡较少。在体内木瓜蛋白酶诱导的 OA 兔模型中，TSMS 还抑制了软骨的退化以及相当大的修复结果以及抑制炎症细胞因子的表达水平，例如肿瘤坏死因子-α (TNF-α) 和白细胞介素-1-β (IL-1β)。总之，TSMS 可以为 OA 的关节内治疗提供非常理想的治疗选择。

重要性声明

骨关节炎（OA）是一种慢性疾病，由关节发炎引起。目前的 OA 治疗可以缓解疼痛，但很难预防或减缓疾病进展。微球处于药物输送和组织工程应用的前沿，也可以微创注射到关节中。多酚和治疗离子已被证明有利于治疗与关节相关的疾病，包括 OA。在此，我们通过静电纺丝结合电喷雾技术制备了基于明胶/聚（L-丙交酯）的纳米纤维微球（MS），并用由 TA 和锶离子（Sr ²⁺）组成的金属酚网络（MPNs）对其进行功能化，并评估了它们OA 治疗的潜力在体外和体内。