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一项安慰剂对照研究比较了关节内注射透明质酸和新型透明质酸-富血小板血浆缀合物在犬骨关节炎模型中的疗效。

A placebo-controlled study comparing the efficacy of intra-articular injections of hyaluronic acid and a novel hyaluronic acid-platelet-rich plasma conjugate in a canine model of osteoarthritis.

机构信息

College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon, 24341, Korea.

ProCore-biomed, Ltd., Weizmann Science Park, 76400, Ness Ziona, Israel.

出版信息

J Orthop Surg Res. 2019 Sep 18;14(1):314. doi: 10.1186/s13018-019-1352-1.

Abstract

BACKGROUND

The objective of this study was to assess the efficacy of intra-articular injections of hyaluronic acid (HA) and a novel, on-site conjugate of HA with autologous fibrinogen in platelet-rich plasma (HA-PRP) in a canine model of osteoarthritis (OA) METHODS: Twelve beagle dogs underwent a unilateral resection of the cranial cruciate ligament (CrCL) of the stifle joint. Clinical and radiographic signs of OA were confirmed in all dogs 8 weeks following CrCL resection and prior to treatment. The dogs were randomized into three groups: saline (n = 4), HA (n = 4), and HA-PRP (n = 4). Each dog received intra-articular injections of the respective substance into the affected joint at pre-determined time points. The dogs were assessed for adverse effects for 3 days after each injection and for lameness, pain, range of motion, kinetics, and radiographic OA severity prior to treatment and 3 months after injection. OA severity as determined by radiographic examination was not significantly different among the groups at any time point. The dogs were then humanely euthanatized and the stifle joint assessed by gross and histological examinations.

RESULTS

Dogs treated with four weekly injections of HA or two biweekly injections of HA-PRP were significantly (p < 0.05) better than dogs treated with four weekly injections of saline at 2-, 4-, and 12-week time points based on a comfortable range of motion (CROM) and clinical lameness score. Gait analysis measuring symmetry and weight distribution on pressure sensor walkway showed significantly (p < 0.05) improved limb function for dogs treated with HA and HA-PRP compared with dogs treated with saline yet with better clinical outcome for the HA-PRP-treated group at 12 and 20 weeks follow-up. Gross and histological analysis of synovium and articular cartilage demonstrated significant (p < 0.05) improvement by both treatments groups compared to controls. There was however significantly (p < 0.05) less damage to the cartilage in the HA-PRP group compared to the HA-treated group.

CONCLUSIONS

These data suggest that while injection of HA and HA-PRP may be sufficient for short-term amelioration of the symptoms associated with OA, treatment with HA-PRP conjugates may be superior, providing significantly better long-term cartilage preservation.

摘要

背景

本研究的目的是评估关节内注射透明质酸(HA)和一种新型 HA 与富含血小板的血浆(HA-PRP)的自体纤维蛋白原缀合物在犬骨关节炎(OA)模型中的疗效。

方法

12 只比格犬接受了膝关节前十字韧带(CrCL)的单侧切除术。所有犬在 CrCL 切除后 8 周且在治疗前均确认出现 OA 的临床和放射学征象。这些狗被随机分为三组:盐水(n = 4)、HA(n = 4)和 HA-PRP(n = 4)。每只狗都在预定时间点向受影响的关节内注射相应的物质。在每次注射后 3 天内评估狗的不良反应,并在治疗前和注射后 3 个月评估跛行、疼痛、运动范围、动力学和放射学 OA 严重程度。在任何时间点,通过放射学检查确定的 OA 严重程度在各组之间均无显著差异。然后对这些狗进行安乐死,并通过大体和组织学检查评估膝关节。

结果

每周注射 4 次 HA 或每两周注射 2 次 HA-PRP 的狗在 2、4 和 12 周时间点的舒适运动范围(CROM)和临床跛行评分方面明显(p < 0.05)优于每周注射 4 次盐水的狗。在压力传感器步道上测量对称性和重量分布的步态分析表明,与接受盐水治疗的狗相比,接受 HA 和 HA-PRP 治疗的狗的肢体功能明显(p < 0.05)改善,但在 12 和 20 周随访时,HA-PRP 治疗组的临床结果更好。滑膜和关节软骨的大体和组织学分析表明,与对照组相比,两组治疗均有明显(p < 0.05)改善。然而,HA-PRP 组的软骨损伤明显(p < 0.05)少于 HA 治疗组。

结论

这些数据表明,尽管注射 HA 和 HA-PRP 可能足以短期缓解与 OA 相关的症状,但治疗用 HA-PRP 缀合物可能更优,可提供明显更好的长期软骨保护。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c732/6749694/26b91294c288/13018_2019_1352_Fig1_HTML.jpg

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