Implant Research Core, School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania, USA.
Johns Hopkins University, Baltimore, Maryland, USA.
J Biomed Mater Res B Appl Biomater. 2021 Oct;109(10):1436-1454. doi: 10.1002/jbm.b.34803. Epub 2021 Jan 22.
For Ti6Al4V orthopedic and spinal implants, osseointegration is often achieved using complex porous geometries created via additive manufacturing (AM). While AM porous titanium (pTi) has shown clinical success, concerns regarding metallic implants have spurred interest in alternative AM biomaterials for osseointegration. Insights regarding the evaluation of these new materials may be supported by better understanding the role of preclinical testing for AM pTi. We therefore asked: (a) What animal models have been most commonly used to evaluate AM porous Ti6Al4V for orthopedic bone ingrowth; (b) What were the primary reported quantitative outcome measures for these models; and (c) What were the bone ingrowth outcomes associated with the most frequently used models? We performed a systematic literature search and identified 58 articles meeting our inclusion criteria. We found that AM pTi was evaluated most often using rabbit and sheep femoral condyle defect (FCD) models. Additional ingrowth models including transcortical and segmental defects, spinal fusions, and calvarial defects were also used with various animals based on the study goals. Quantitative outcome measures determined via histomorphometry including ''bone ingrowth'' (range: 3.92-53.4% for rabbit/sheep FCD) and bone-implant contact (range: 9.9-59.7% for rabbit/sheep FCD) were the most common. Studies also used 3D imaging to report outcomes such as bone volume fraction (BV/TV, range: 4.4-61.1% for rabbit/sheep FCD), and push-out testing for outcomes such as maximum removal force (range: 46.6-3092 N for rabbit/sheep FCD). Though there were many commonalities among the study methods, we also found significant heterogeneity in the outcome terms and definitions. The considerable diversity in testing and reporting may no longer be necessary considering the reported success of AM pTi across all model types and the ample literature supporting the rabbit and sheep as suitable small and large animal models, respectively. Ultimately, more standardized animal models and reporting of bone ingrowth for porous AM materials will be useful for future studies.
对于骨科和脊柱植入物用 Ti6Al4V，通过增材制造（AM）创建复杂的多孔几何形状通常可实现骨整合。虽然 AM 多孔钛（pTi）已显示出临床成功，但对金属植入物的担忧促使人们对用于骨整合的替代 AM 生物材料产生兴趣。对这些新材料的评估见解可能会通过更好地理解 AM pTi 临床前测试的作用而得到支持。因此，我们提出了以下三个问题：（a）为了评估用于骨科骨内生长的 AM 多孔 Ti6Al4V，最常使用哪些动物模型；（b）这些模型的主要报告的定量结果衡量标准是什么；（c）最常使用的模型与哪些骨内生长结果相关？我们进行了系统的文献检索，确定了符合纳入标准的 58 篇文章。我们发现，AM pTi 最常使用兔和绵羊股骨髁缺损（FCD）模型进行评估。根据研究目标，还使用了其他内生长模型，包括皮质骨和节段性缺损、脊柱融合和颅骨缺损，并使用了各种动物。通过组织形态计量学确定的定量结果衡量标准包括“骨内生长”（兔/绵羊 FCD 的范围为 3.92-53.4%）和骨-植入物接触（兔/绵羊 FCD 的范围为 9.9-59.7%），是最常见的。研究还使用 3D 成像来报告骨体积分数（BV/TV，兔/绵羊 FCD 的范围为 4.4-61.1%）等结果，以及推挤试验等结果，如最大去除力（兔/绵羊 FCD 的范围为 46.6-3092N）。尽管研究方法有许多共同点，但我们也发现结果术语和定义存在很大差异。考虑到 AM pTi 在所有模型类型上的报告成功以及充分的文献支持兔和绵羊分别作为小型和大型动物模型的适用性，测试和报告方面的这种巨大差异可能不再必要。最终，对于多孔 AM 材料的骨内生长，更标准化的动物模型和报告将有助于未来的研究。
