Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), Dublin, 2 D02 YN77, Ireland.
Advanced Materials Bio-Engineering Research Centre (AMBER), RCSI and TCD, Dublin, 2 D02 PN40, Ireland.
Adv Healthc Mater. 2021 Oct;10(20):e2100878. doi: 10.1002/adhm.202100878. Epub 2021 Aug 18.
Joint repair remains a major challenge in orthopaedics. Recent progress in biomaterial design has led to the fabrication of a plethora of promising devices. Pre-clinical testing of any joint repair strategy typically requires the use of large animal models (e.g., sheep, goat, pig or horse). Despite the key role of such models in clinical translation, there is still a lack of consensus regarding optimal experimental design, making it difficult to draw conclusions on their efficacy. In this context, the authors performed a systematic literature review and a risk of bias assessment on large animal models published between 2010 and 2020, to identify key experimental parameters that significantly affect the biomaterial therapeutic outcome and clinical translation potential (including defect localization, animal age/maturity, selection of controls, cell-free versus cell-laden). They determined that mechanically strong biomaterials perform better at the femoral condyles; while highlighted the importance of including native tissue controls to better evaluate the quality of the newly formed tissue. Finally, in cell-laded biomaterials, the pre-culture conditions played a more important role in defect repair than the cell type. In summary, here they present a systematic evaluation on how the experimental design of preclinical models influences biomaterial-based therapeutic outcomes in joint repair.
关节修复仍然是骨科领域的一大挑战。生物材料设计的最新进展已经导致了大量有前途的设备的出现。任何关节修复策略的临床前测试通常都需要使用大型动物模型(例如绵羊、山羊、猪或马)。尽管这些模型在临床转化中起着关键作用,但对于最佳实验设计仍缺乏共识,因此难以就其疗效得出结论。在这种情况下,作者对 2010 年至 2020 年间发表的大型动物模型进行了系统的文献综述和偏倚风险评估,以确定对生物材料治疗结果和临床转化潜力有重大影响的关键实验参数(包括缺陷定位、动物年龄/成熟度、对照选择、无细胞与细胞负载)。他们确定机械强度高的生物材料在股骨髁处表现更好;同时强调了包括天然组织对照的重要性,以更好地评估新形成组织的质量。最后,在细胞负载的生物材料中,预培养条件在缺陷修复中的作用比细胞类型更重要。总之,他们在这里系统地评估了临床前模型的实验设计如何影响关节修复中的基于生物材料的治疗效果。