骨科创伤的临床前模型:骨科研究学会(ORS)和创伤骨科协会(OTA)2022 年研讨会。

Patrick M Wise, Augustine M Saiz, Justin Haller, Joseph C Wenke, Thomas Schaer, Prism Schneider, Saam Morshed, Chelsea S Bahney
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引用次数: 0

摘要

骨科创伤仍然是造成患者发病率、死亡率和全球医疗负担的主要原因。尽管在这些创伤的诊断、治疗和康复方面已取得了重大进展,但仍会出现一些并发症,如骨折愈合不良、骨折不愈合、感染、废用性肌肉萎缩和骨质疏松,以及无法完全恢复基线功能等。骨折治疗中固有的重大临床变异,如不同的患者人口统计学特征、损伤模式和治疗方案,使得标准化和可复制的研究,尤其是基于细胞和分子机制的研究几乎不可能实现。因此,致力于改善骨科创伤患者疗法和治疗方法的科学家依赖于临床前模型。事实证明,临床前模型在了解植入物插入和细菌接种之间的时机对感染生物负荷的影响方面非常有价值。创伤后关节炎(PTOA)可能需要数年时间才能在临床上形成,但通过猪脊柱骨折模型,可以可靠地诱发创伤后关节炎,从而可以测试不同的手术和治疗策略以进行预防。相反,赛马是自然发生的创伤后关节炎的公认模型。临床前多创伤模型以胸部损伤、腹部损伤、多发性骨折和/或头部损伤为主,可以系统地研究各种损伤模式对骨折愈合的影响。最后,这些临床前模型可作为转化桥梁,将其应用于人类患者的临床治疗。通过选择合适的临床前模型,研究可以建立一个平台,降低新兴技术的风险,并为治疗性临床试验提供基础支持。总之,骨科创伤临床前模型可以让科学家简化复杂的临床挑战,从低等脊椎动物模型开始了解基本途径。然后,将研发工作推进到高等脊椎动物模型,以增加研究结果转化为临床实践的复杂性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Preclinical models of orthopaedic trauma: Orthopaedic Research Society (ORS) and Orthopaedic Trauma Association (OTA) symposium 2022.

Orthopaedic trauma remains a leading cause of patient morbidity, mortality, and global health care burden. Although significant advances have been made in the diagnosis, treatment, and rehabilitation of these injuries, complications such as malunion, nonunion, infection, disuse muscle atrophy and osteopenia, and incomplete return to baseline function still occur. The significant inherent clinical variability in fracture care such as differing patient demographics, injury patterns, and treatment protocols make standardized and replicable study, especially of cellular and molecular based mechanisms, nearly impossible. Hence, the scientists dedicated to improving therapy and treatments for patients with orthopaedic trauma rely on preclinical models. Preclinical models have proven to be invaluable in understanding the timing between implant insertion and bacterial inoculation on the bioburden of infection. Posttraumatic arthritis (PTOA) can take years to develop clinically, but with a porcine pilon fracture model, posttraumatic arthritis can be reliably induced, so different surgical and therapeutic strategies can be tested in prevention. Conversely, the racehorse presents a well-accepted model of naturally occurring PTOA. With preclinical polytrauma models focusing on chest injury, abdominal injury, multiple fractures, and/or head injury, one can study how various injury patterns affect fracture healing can be systemically studied. Finally, these preclinical models serve as a translational bridge to for clinical application in human patients. With selection of the right preclinical model, studies can build a platform to decrease the risk of emerging technologies and provide foundational support for therapeutic clinical trials. In summary, orthopaedic trauma preclinical models allow scientists to simplify a complex clinical challenge, to understand the basic pathways starting with lower vertebrate models. Then, R&D efforts progress to higher vertebrate models to build in more complexity for translation of findings to the clinical practice.

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