Currently there are no standard models with which to evaluate the biomechanical performance of calcified tissue adhesives, in vivo. We present, herein, a pre-clinical murine distal femoral bone model for evaluating tissue adhesives intended for use in both osseous and osteochondral tissue reconstruction. Cylindrical cores (diameter (Ø) 2 mm (mm) × 2 mm depth), containing both cancellous and cortical bone, were fractured out from the distal femur and then reattached using one of two tissue adhesives. The adhesiveness of fibrin glue (Tisseeltm), and a novel, biocompatible, calcium phosphate-based tissue adhesive (OsStictm) were evaluated by pullout testing, in which glued cores were extracted and the peak force at failure recorded. The results show that Tisseel weakly bonded the metaphyseal bone cores, while OsStic produced > 30-fold higher mean peak forces at failure (7.64 Newtons (N) vs. 0.21 N). The failure modes were consistently disparate, with Tisseel failing gradually, while OsStic failed abruptly, as would be expected with a calcium-based material. Imaging of the bone/adhesive interface with microcomputed tomography revealed that, for OsStic, failure occurred more often within cancellous bone (75% of tested samples) rather than at the adhesive interface. Despite the challenges associated with biomechanical testing in small rodent models the preclinical ex-vivo test model presented herein is both sensitive and accurate. It enabled differences in tissue adhesive strength to be quantified even for very small osseous fragments (<Ø4mm). Importantly, this model can easily be scaled to larger animals and adapted to fracture fragment fixation in human bone. The present model is also compatible with other long-term in vivo evaluation methods (i.e. in vivo imaging, histological analysis, etc.).

中文翻译：

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用于评估骨和骨软骨组织粘合剂的生物力学测试模型。

目前还没有标准模型来评估体内钙化组织粘合剂的生物力学性能。我们在此展示了一种临床前小鼠股骨远端骨模型，用于评估用于骨和骨软骨组织重建的组织粘合剂。包含松质骨和皮质骨的圆柱形芯（直径 (Ø) 2 mm (mm) × 2 mm 深度）从股骨远端折断，然后使用两种组织粘合剂中的一种重新连接。通过拔出测试评估了纤维蛋白胶 (Tisseltm) 和新型生物相容性磷酸钙基组织粘合剂 (OsStictm) 的粘合性，其中胶合芯被提取并记录失效时的峰值力。结果表明，Tisseel 弱结合干骺端骨核，而 OsStic 产生 > 失效时的平均峰值力高出 30 倍（7.64 牛顿 (N) 与 0.21 N）。失效模式始终不同，Tisseel 逐渐失效，而 OsStic 突然失效，正如钙基材料所预期的那样。使用微型计算机断层扫描对骨/粘合剂界面进行成像显示，对于 OsStic，失效更常见于松质骨（75% 的测试样品）而不是粘合剂界面。尽管在小型啮齿动物模型中进行生物力学测试存在挑战，但本文提出的临床前离体测试模型既灵敏又准确。即使对于非常小的骨碎片（<Ø4mm），它也可以量化组织粘合强度的差异。重要的是，这个模型可以很容易地扩展到更大的动物，并适应人体骨骼中的骨折碎片固定。