Orthopedics and Sports Medicine Center, The Affiliated Suzhou Hospital of Nanjing Medical University, 242 Guangji Road, Suzhou, 215006, PR China; Gusu School, Nanjing Medical University, 458 Shizi Road, Suzhou, 215006, PR China.
Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, PR China.
Biomaterials. 2022 Jun;285:121545. doi: 10.1016/j.biomaterials.2022.121545. Epub 2022 Apr 27.
Nanofat (NF) is a fine emulsion that has been used to treat a variety of diseases given its abundance of bioactive components. However, the biological functions of NF have been limited due to its inability to localize during implantation. In this study, NF was immobilized in microfluidic-generated aldehyde-modified polylactic glycolic acid (PLGA) porous microspheres (PMs) via Schiff base condensation and non-covalent binding in a three-dimensional (3D) porous network (PMs@NF). The PMs effectively enhanced the cartilage-targeted retention efficiency of NF, which also resulted in remarkable lubrication performance, with the friction coefficient being reduced by ∼80%, which was maintained over time. Meanwhile, the 3D penetrating structure of the microspheres stimulated cytokine secretion by the NF-derived stem cells, upregulating the expression of anabolism-related genes and downregulating catabolism, and the expression of inflammation-related and pain-related genes. Injecting PMs@NF into the knee joint cavity of a rat model with destabilization of the medial meniscus (DMM) reduced osteophyte formation and protected the cartilage from degeneration, thereby inhibiting the progression of osteoarthritis and improving animal behavior. In summary, this study developed a multifunctional platform with NF immobilization and super-lubrication, which showed great potential for the minimally invasive treatment of osteoarthritis.
纳米脂肪（NF）是一种精细乳液，由于其含有丰富的生物活性成分，已被用于治疗多种疾病。然而，由于在植入过程中无法定位，NF 的生物学功能受到限制。在这项研究中，NF 通过席夫碱缩合和非共价键结合被固定在微流控生成的醛修饰的聚乳酸-乙醇酸（PLGA）多孔微球（PMs）中，形成三维（3D）多孔网络（PMs@NF）。PMs 有效地提高了 NF 的软骨靶向保留效率，同时还具有显著的润滑性能，摩擦系数降低了约 80%，并且随着时间的推移保持稳定。同时，微球的 3D 穿透结构刺激 NF 衍生的干细胞分泌细胞因子，上调与合成代谢相关的基因的表达，下调与分解代谢相关的基因的表达，以及炎症相关和疼痛相关基因的表达。将 PMs@NF 注射到内侧半月板不稳定（DMM）大鼠模型的膝关节腔中，可减少骨赘形成并保护软骨免受退化，从而抑制骨关节炎的进展并改善动物行为。总之，本研究开发了一种具有 NF 固定和超润滑功能的多功能平台，为微创治疗骨关节炎提供了巨大的潜力。
