Department of Orthopaedic Surgery, University of California, San Diego, California 94143-0514, USA.
Tissue Eng Part B Rev. 2010 Feb;16(1):147-58. doi: 10.1089/ten.TEB.2009.0451.
The development of tissue engineering therapies for the intervertebral disc is challenging due to ambiguities of disease and pain mechanisms in patients, and lack of consensus on preclinical models for safety and efficacy testing. Although the issues associated with model selection for studying orthopedic diseases or treatments have been discussed often, the multifaceted challenges associated with developing intervertebral disc tissue engineering therapies require special discussion. This review covers topics relevant to the clinical translation of tissue-engineered technologies: (1) the unmet clinical need, (2) appropriate models for safety and efficacy testing, (3) the need for standardized model systems, and (4) the translational pathways leading to a clinical trial. For preclinical evaluation of new therapies, we recommend establishing biologic plausibility of efficacy and safety using models of increasing complexity, starting with cell culture, small animals (rats and rabbits), and then large animals (goat and minipig) that more closely mimic nutritional, biomechanical, and surgical realities of human application. The use of standardized and reproducible experimental procedures and outcome measures is critical for judging relative efficacy. Finally, success will hinge on carefully designed clinical trials with well-defined patient selection criteria, gold-standard controls, and objective outcome metrics to assess performance in the early postoperative period.
由于患者疾病和疼痛机制的不明确，以及缺乏安全和疗效测试的临床前模型共识，开发用于治疗椎间盘的组织工程疗法具有挑战性。尽管人们经常讨论与研究骨科疾病或治疗方法相关的模型选择问题，但开发椎间盘组织工程疗法所涉及的多方面挑战需要特别讨论。这篇综述涵盖了与组织工程技术临床转化相关的主题：（1）未满足的临床需求，（2）用于安全性和疗效测试的合适模型，（3）标准化模型系统的需求，以及（4）通向临床试验的转化途径。对于新疗法的临床前评估，我们建议使用越来越复杂的模型来建立疗效和安全性的生物学合理性，从细胞培养、小型动物（大鼠和兔子）开始，然后是更接近人类应用的营养、生物力学和手术现实的大型动物（山羊和迷你猪）。使用标准化和可重复的实验程序和结果测量对于判断相对疗效至关重要。最后，成功将取决于精心设计的临床试验，这些临床试验具有明确的患者选择标准、黄金标准对照和客观的结果指标，以评估术后早期的性能。
