La Gatta Annalisa, Stellavato Antonietta, Vassallo Valentina, Di Meo Celeste, Toro Giuseppe, Iolascon Giovanni, Schiraldi Chiara
Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Via De Crecchio 7, 80138 Naples, Italy.
Department of Medical and Surgical Specialties and Dentistry, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.
Polymers (Basel). 2021 Sep 22;13(19):3208. doi: 10.3390/polym13193208.
In this research work, viscosupplements based on linear, derivatized, crosslinked and complexed HA forms were extensively examined, providing data on the hydrodynamic parameters for the water-soluble-HA-fraction, rheology, sensitivity to enzymatic hydrolysis and capacity to modulate specific biomarkers' expression in human pathological chondrocytes and synoviocytes. Soluble HA ranged from 0 to 32 mg/mL and from 150 to 1330 kDa MW. The rheological behavior spanned from purely elastic to viscoelastic, suggesting the diversity of the categories that are suitable for restoring specific/different features of the healthy synovial fluid. The rheological parameters were reduced in a diverse manner upon dilution and hyaluronidases action, indicating different durations of the viscosupplementation effect. Bioactivity was found for all the samples, increasing the expression of different matrix markers (e.g., hyaluronan-synthase); however, the hybrid cooperative complexes performed better in most of the experiments. Hybrid cooperative complexes improved COLII mRNA expression (~12-fold increase vs. CTR), proved the most effective at preserving cell phenotype. In addition, in these models, the HA samples reduced inflammation. IL-6 was down-regulated vs. CTR by linear and chemically modified HA, and especially by hybrid complexes. The results represent the first comprehensive panel of data directly comparing the diverse HA forms for intra-articular injections and provide valuable information for tailoring products' clinical use as well as for designing new, highly performing HA-formulations that can address specific needs.
在这项研究工作中，对基于线性、衍生化、交联和复合形式的透明质酸（HA）的粘性补充剂进行了广泛研究，提供了关于水溶性HA组分的流体动力学参数、流变学、对酶促水解的敏感性以及调节人类病理性软骨细胞和滑膜细胞中特定生物标志物表达能力的数据。可溶性HA的浓度范围为0至32mg/mL，分子量范围为150至1330kDa。流变行为从纯弹性到粘弹性不等，表明适合恢复健康滑液特定/不同特征的类别具有多样性。稀释和透明质酸酶作用后，流变学参数以不同方式降低，表明粘性补充效果的持续时间不同。所有样品均具有生物活性，可增加不同基质标志物（如透明质酸合酶）的表达；然而，在大多数实验中，混合协同复合物表现更好。混合协同复合物改善了II型胶原蛋白（COLII）mRNA的表达（与对照组相比增加约12倍），证明在维持细胞表型方面最有效。此外，在这些模型中，HA样品减轻了炎症。与对照组相比，线性和化学修饰的HA，尤其是混合复合物，下调了白细胞介素-6（IL-6）的表达。这些结果代表了首个直接比较用于关节内注射的不同HA形式的全面数据集，并为定制产品的临床应用以及设计能够满足特定需求的新型高性能HA制剂提供了有价值的信息。
