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水凝胶构建体在马模型中用于软骨修复的固定:一个具有挑战性的问题。

Fixation of Hydrogel Constructs for Cartilage Repair in the Equine Model: A Challenging Issue.

机构信息

1 Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University , Utrecht, The Netherlands .

2 Cátedra de Cirugía de Especies Mayores, Escuela de Medicina Veterinaria, Universidad Nacional , Heredia, Costa Rica .

出版信息

Tissue Eng Part C Methods. 2017 Nov;23(11):804-814. doi: 10.1089/ten.TEC.2017.0200.

Abstract

OBJECTIVE

To report on the experiences with the use of commercial and autologous fibrin glue (AFG) and of an alternative method based on a 3D-printed polycaprolactone (PCL) anchor for the fixation of hydrogel-based scaffolds in an equine model for cartilage repair.

METHODS

In a first study, three different hydrogel-based materials were orthotopically implanted in nine horses for 1-4 weeks in 6 mm diameter full-thickness cartilage defects in the medial femoral trochlear ridge and fixated with commercially available fibrin glue (CFG). One defect was filled with CFG only as a control. In a second study, CFG and AFG were compared in an ectopic equine model. The third study compared the efficacy of AFG and a 3D-printed PCL-based osteal anchor for fixation of PCL-reinforced hydrogels in three horses for 2 weeks, with a 4-week follow-up to evaluate integration of bone with the PCL anchor. Short-term scaffold integration and cell infiltration were evaluated by microcomputed tomography and histology as outcome parameters.

RESULTS

The first study showed signs of subchondral bone resorption in all defects, including the controls filled with CFG only, with significant infiltration of neutrophils. Ectopically, CFG induced clear inflammation with strong neutrophil accumulation; AFG was less reactive, showing fibroblast infiltration only. In the third study the fixation potential for PCL-reinforced hydrogels of AFG was inferior to the PCL anchor. PCL reinforcement had disappeared from two defects and showed signs of dislodging in the remaining four. All six constructs fixated with the PCL anchor were still in place after 2 weeks. At 4 weeks, the PCL anchor showed good integration and signs of new bone formation.

CONCLUSIONS

The use of AFG should be preferred to xenogeneic products in the horse, but AFG is subject to individual variations and laborious to make. The PCL anchor provides the best fixation; however, this technique involves the whole osteochondral unit, which entails a different conceptual approach to cartilage repair.

摘要

目的

报告在马模型中使用商业纤维蛋白胶(CFG)和同种异体纤维蛋白胶(AFG)以及基于 3D 打印聚己内酯(PCL)锚的替代方法固定水凝胶支架的经验,用于软骨修复。

方法

在第一项研究中,将三种不同的水凝胶基材料原位植入 9 匹马的内侧股骨滑车嵴 6mm 直径全层软骨缺损中,1-4 周,用市售纤维蛋白胶(CFG)固定。一个缺陷仅用 CFG 填充作为对照。在第二项研究中,在异位马模型中比较了 CFG 和 AFG。第三项研究比较了 AFG 和 3D 打印 PCL 基骨锚固定 PCL 增强水凝胶的效果,在 3 匹马中固定 2 周,4 周后评估 PCL 锚与骨的整合情况。短期支架整合和细胞浸润通过微计算机断层扫描和组织学作为结果参数进行评估。

结果

第一项研究表明,所有缺陷(包括仅用 CFG 填充的对照)均出现软骨下骨吸收迹象,包括仅用 CFG 填充的对照,中性粒细胞明显浸润。异位 CFG 诱导明显炎症,中性粒细胞大量积聚;AFG 反应性较低,仅表现为成纤维细胞浸润。在第三项研究中,AFG 对 PCL 增强水凝胶的固定潜力不如 PCL 锚。两个缺陷的 PCL 增强已经消失,其余四个缺陷有移位迹象。用 PCL 锚固定的所有六个构建体在 2 周后仍在原位。4 周时,PCL 锚显示出良好的整合和新骨形成的迹象。

结论

在马中应优先使用 AFG 代替异种产品,但 AFG 存在个体差异,且制作费力。PCL 锚提供最佳固定;然而,这种技术涉及整个骨软骨单元,需要对软骨修复有不同的概念方法。

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