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Can Genipin-coated Sutures Deliver a Collagen Crosslinking Agent to Improve Suture Pullout in Degenerated Tendon? An Ex Vivo Animal Study

机译:Genipin涂层缝合线可以递送胶原蛋白交联剂,以改善退化的肌腱中的缝线拉出? exvivo动物研究

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BackgroundThe suture-tendon interface is often the weakest link in tendon-to-tendon or tendon-to-bone repair. Genipin is an exogenous collagen crosslink agent derived from the gardenia fruit that can enhance suture force to failure of the tendon-suture interface. Viable methods for intraoperative clinical delivery of genipin could be of clinical utility, but to our knowledge have not yet been extensively studied.Questions/purposesThe purposes of this study were (1) to evaluate whether sutures precoated with genipin can augment the suture-tendon interface to improve force to failure, stiffness, and work to failure in healthy and degenerated tendons; and (2) to determine the effect of genipin on the extent and distribution of crosslinking.MethodsSingle-stitch suture pullout tests were performed ex vivo on 25 bovine superficial digital flexor tendons. To assess effects on native tissue, one group of 12 tendons was cut in proximal and distal halves and randomized to treatment (n = 12) and control groups (n = 12) in a matched-pair design. One simple stitch with a loop with either a normal suture or genipin-coated suture was applied to tendons in both groups. To simulate a degenerative tendon condition, a second group of 13 tendons was cut in proximal and distal halves, injected with 0.2 mL of collagenase D (8 mg/mL) and incubated for 24 hours before suturing with either a genipin-coated suture (n = 13) or their matched controls (n = 13). Sutures from all groups then were loaded to failure on a universal materials testing machine 24 hours after suturing. Suture pullout force, stiffness, and work to failure were calculated from force-displacement data and compared between the groups. Additionally, fluorescence was measured to determine the degree of crosslinking quantitatively and a qualitative analysis of the distribution pattern was performed by microscopy.ResultsIn healthy tendon pairs, the median maximum pullout force was greater with genipin-coated sutures than with control sutures (median, 42 N [range, 24-73 N] versus 29 N [range, 13-48 N]; difference of medians, 13 N; p = 0.003) with corresponding increases in the required work to failure (median, 275 mJ [range, 48-369 mJ] versus 148 mJ [range, 83-369 mJ]; difference of medians, 127 mJ; p = 0.025) but not stiffness (median, 4.1 N/mm [range, 2.3-8.1 N/mm] versus 3.3 N/mm [range, 1.1-9.6 N/mm]; difference of medians, 0.8 N/mm; p = 0.052). In degenerated tendons, median maximum pullout force was greater with genipin-coated sutures than with control sutures (median, 16 N [range, 9-36 N] versus 13 N [range, 5-28 N]; difference of medians, 3 N; p = 0.034) with no differences in work to failure (median, 75 mJ [range, 11-249 mJ] versus 53 mJ [range, 14-143 mJ]; difference of medians, 22 mJ; p = 0.636) or stiffness (median, 1.9 N/mm [range, 0.7-13.4 N/mm] versus 1.6 N/mm [range, 0.5-5.6 N/mm]; difference of medians, 0.3 N/mm; p = 0.285). Fluorescence was higher in tendons treated with genipin-coated sutures compared with the control group, whereas higher fluorescence was observed in the treated healthy compared with the degenerated tendons (difference of means -3.16; standard error 1.08; 95% confidence interval [CI], 0.97-5.34; p = 0.006/healthy genipin: mean 13.04; standard error 0.78; 95% CI, 11.47-14.62; p 0.001/degenerated genipin: mean 9.88; SD 0.75; 95% CI, 8.34-11.40; p 0.001).ConclusionsGenipin-coated sutures improved force to failure of a simple stitch at the tendon-suture interface in healthy and degenerated tendons in an ex vivo animal model.
机译:背景技术缝合线腱界面通常是肌腱到肌腱或肌腱到骨骼修复中最弱的环节。 Genipin是衍生自栀子果实的外源胶原蛋白交联剂,可以增强肌腱缝合线界面的缝合力。术中临床递送的可行方法可以是临床效用,但对于我们的知识尚未广泛研究。追踪/目的,本研究的目的是(1)评估是否预先用Genipin预先预浸的缝合线可以增强缝合线界面。改善失败,僵硬,并在健康和退化的肌腱上工作的力量; (2)确定Genipin对交联的程度和分布的影响。在25牛浅表的数字屈肌肌腱上进行了前体内的方法。为了评估对天然组织的影响,将一组12个筋在近端和远端切割,并在匹配对设计中随机地进行处理(n = 12)和对照组(n = 12)。将具有正常缝合线或Genipin涂层缝合线的环的一个简单针脚施用于两个组中的肌腱。为了模拟退化肌腱条件,将第二组13个筋在近端和远端切割,注入0.2ml胶原酶D(8mg / ml),并在用Genipin涂覆的缝合线缝合之前24小时温育(n = 13)或其匹配的控制(n = 13)。然后,所有群体的缝线都在缝合后24小时内装载到通用材料试验机上的故障。缝合拉伸力,刚度和失败的工作是从力位移数据计算的,并在组之间进行比较。另外,测量荧光以定量地确定交联程度,并通过显微镜进行分布模式的定性分析。结果是健康的肌腱对,中位最大拉伸力与Genipin涂层缝合线大于控制缝合线(中位数,42 n [范围,24-73 n]与29 n [范围,13-48 n];中位数,13 n; p = 0.003)的差异相应的失效工作增加(中位数,275 mj [范围,48 -369 MJ]与148 MJ [范围,83-369 MJ];中位数,127 MJ; P = 0.025的差异)但不是刚度(中位数,4.1n / mm [范围,2.3-8.1n / mm]与3.3 n / mm [范围,1.1-9.6 n / mm];中位数的差异,0.8 n / mm; p = 0.052)。在退化的肌腱中,与对照缝合线(中位数,16 = 9-36 n]与13 n [范围,5-28 n]相比,旋脂囊缝管的中位数最大拉出力大于较大的滞后力。中位数的差异,3 n ; P = 0.034)在失败的工作中没有差异(中位数,75 MJ [范围,11-249 MJ]与53 MJ [范围,14-143 MJ];中位数,22 MJ; P = 0.636的差异)或刚度(中位数,1.9 n / mm [范围,0.7-13.4 n / mm]与1.6 n / mm [范围,0.5-5.6 n / mm];中位数的差异,0.3 n / mm; p = 0.285)。与对照组相比,用Genipin涂覆的缝合线处理的肌腱中荧光较高,而与再生肌腱相比,在处理的健康中观察到更高的荧光(平移-3.16;标准误差1.08; 95%置信区间[CI], 0.97-5.34; p = 0.006 /健康Genipin:平均13.04;标准误差0.78; 95%CI,11.47-14.62; P <0.001 /退化的Genipin:平均9.88; SD 0.75; 95%CI,8.34-11.40; P&LT ; 0.001)。结论预后涂覆的缝合线改善了在前体内动物模型中健康和退化肌腱中肌腱缝合界面的简单针脚失效的力。

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