Department of Orthopaedics, Dartmouth-Hitchcock Medical Centre, Lebanon, New Hampshire, USA.
Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, USA.
J Orthop Res. 2023 May;41(5):1040-1048. doi: 10.1002/jor.25443. Epub 2022 Oct 3.
High-energy orthopedic injuries cause severe damage to soft tissues and are prone to infection and healing complications, making them a challenge to manage. Further research is facilitated by a clinically relevant animal model with commensurate fracture severity and soft-tissue damage, allowing evaluation of novel treatment options and techniques. Here we report a reproducible, robust, and clinically relevant animal model of high-energy trauma with extensive soft-tissue damage, based on compressed air-driven membrane rupture as the blast wave source. As proof-of-principle showing the reproducibility of the injury, we evaluate changes in tissue and bone perfusion for a range of different tibia fracture severities, using dynamic contrast-enhanced fluorescence imaging and microcomputed tomography. We demonstrate that fluorescence tracer temporal profiles for skin, femoral vein, fractured bone, and paw reflect the increasing impact of more powerful blasts causing a range of Gustilo grade I-III injuries. The maximum fluorescence intensity of distal tibial bone following 0.1 mg/kg intravenous indocyanine green injection decreased by 35% (p < 0.01), 75% (p < 0.001), and 87% (p < 0.001), following grade I, II, and III injuries, respectively, compared to uninjured bone. Other kinetic parameters of bone and soft tissue perfusion extracted from series of fluorescence images for each animal also showed an association with severity of trauma. In addition, the time-intensity profile of fluorescence showed marked differences in wash-in and wash-out patterns for different injury severities and anatomical locations. This reliable and realistic high-energy trauma model opens new research avenues to better understand infection and treatment strategies. Level of evidence: Level III; Case-control.
高能骨科损伤会对软组织造成严重损害,容易感染和愈合并发症,因此难以处理。通过具有相当骨折严重程度和软组织损伤的临床相关动物模型,可以促进进一步的研究,从而评估新的治疗选择和技术。在这里,我们报告了一种基于压缩空气驱动的膜破裂作为爆炸波源的高能创伤的具有广泛软组织损伤的可重现、稳健且临床相关的动物模型。作为损伤可重现性的原理证明,我们使用动态对比增强荧光成像和微计算机断层扫描评估了不同胫骨骨折严重程度的组织和骨灌注变化。我们证明,皮肤、股静脉、骨折骨和爪子的荧光示踪剂时间曲线反映了更强大的爆炸造成的一系列 Gustilo 分级 I-III 损伤的影响越来越大。与未受伤的骨骼相比,在 0.1mg/kg 静脉注射吲哚菁绿后,0.1mg/kg 静脉注射吲哚菁绿后,最大荧光强度分别降低了 35%(p<0.01)、75%(p<0.001)和 87%(p<0.001),分别为 I 级、II 级和 III 级损伤。从每个动物的一系列荧光图像中提取的骨和软组织灌注的其他动力学参数也显示出与创伤严重程度的关联。此外,荧光的时间-强度曲线显示,不同损伤严重程度和解剖部位的灌注冲洗和冲洗模式存在明显差异。这种可靠且现实的高能创伤模型为更好地理解感染和治疗策略开辟了新的研究途径。证据水平:III 级;病例对照。