Centre for Orthopaedic and Trauma Research, Adelaide Medical School, The University of Adelaide, Adelaide, Australia.
School of Mechanical Engineering, The University of Adelaide, Adelaide, Australia.
Clin Orthop Relat Res. 2022 Nov 1;480(11):2232-2250. doi: 10.1097/CORR.0000000000002327. Epub 2022 Aug 24.
A nanostructured titanium surface that promotes antimicrobial activity and osseointegration would provide the opportunity to create medical implants that can prevent orthopaedic infection and improve bone integration. Although nanostructured surfaces can exhibit antimicrobial activity, it is not known whether these surfaces are safe and conducive to osseointegration.
QUESTIONS/PURPOSES: Using a sheep animal model, we sought to determine whether the bony integration of medical-grade, titanium, porous-coated implants with a unique nanostructured surface modification (alkaline heat treatment [AHT]) previously shown to kill bacteria was better than that for a clinically accepted control surface of porous-coated titanium covered with hydroxyapatite (PCHA) after 12 weeks in vivo. The null hypothesis was that there would be no difference between implants with respect to the primary outcomes: interfacial shear strength and percent intersection surface (the percentage of implant surface with bone contact, as defined by a micro-CT protocol), and the secondary outcomes: stiffness, peak load, energy to failure, and micro-CT (bone volume/total volume [BV/TV], trabecular thickness [Tb.Th], and trabecular number [Tb.N]) and histomorphometric (bone-implant contact [BIC]) parameters.
Implants of each material (alkaline heat-treated and hydroxyapatite-coated titanium) were surgically inserted into femoral and tibial metaphyseal cancellous bone (16 per implant type; interference fit) and in tibial cortices at three diaphyseal locations (24 per implant type; line-to-line fit) in eight skeletally mature sheep. At 12 weeks postoperatively, bones were excised to assess osseointegration of AHT and PCHA implants via biomechanical push-through tests, micro-CT, and histomorphometry. Bone composition and remodeling patterns in adult sheep are similar to that of humans, and this model enables comparison of implants with ex vivo outcomes that are not permissible with humans. Comparisons of primary and secondary outcomes were undertaken with linear mixed-effects models that were developed for the cortical and cancellous groups separately and that included a random effect of animals, covariates to adjust for preoperative bodyweight, and implant location (left/right limb, femoral/tibial cancellous, cortical diaphyseal region, and medial/lateral cortex) as appropriate. Significance was set at an alpha of 0.05.
The estimated marginal mean interfacial shear strength for cancellous bone, adjusted for covariates, was 1.6 MPa greater for AHT implants (9.3 MPa) than for PCHA implants (7.7 MPa) (95% CI 0.5 to 2.8; p = 0.006). Similarly, the estimated marginal mean interfacial shear strength for cortical bone, adjusted for covariates, was 6.6 MPa greater for AHT implants (25.5 MPa) than for PCHA implants (18.9 MPa) (95% CI 5.0 to 8.1; p < 0.001). No difference in the implant-bone percent intersection surface was detected for cancellous sites (cancellous AHT 55.1% and PCHA 58.7%; adjusted difference of estimated marginal mean -3.6% [95% CI -8.1% to 0.9%]; p = 0.11). In cortical bone, the estimated marginal mean percent intersection surface at the medial site, adjusted for covariates, was 11.8% higher for AHT implants (58.1%) than for PCHA (46.2% [95% CI 7.1% to 16.6%]; p < 0.001) and was not different at the lateral site (AHT 75.8% and PCHA 74.9%; adjusted difference of estimated marginal mean 0.9% [95% CI -3.8% to 5.7%]; p = 0.70).
These data suggest there is stronger integration of bone on the AHT surface than on the PCHA surface at 12 weeks postimplantation in this sheep model.
Given that the AHT implants formed a more robust interface with cortical and cancellous bone than the PCHA implants, a clinical noninferiority study using hip stems with identical geometries can now be performed to compare the same surfaces used in this study. The results of this preclinical study provide an ethical baseline to proceed with such a clinical study given the potential of the alkaline heat-treated surface to reduce periprosthetic joint infection and enhance implant osseointegration.
具有抗菌活性和骨整合能力的纳米结构钛表面将为制造能够预防骨科感染和改善骨整合的医用植入物提供机会。尽管纳米结构表面可以表现出抗菌活性，但尚不清楚这些表面是否安全且有利于骨整合。
问题/目的：使用绵羊动物模型，我们旨在确定先前显示具有杀菌作用的医疗级钛多孔涂层具有独特纳米结构表面改性（碱性热处理 [AHT]）的多孔涂层钛植入物的骨整合是否优于临床接受的多孔涂层羟基磷灰石覆盖的表面（PCHA）在体内 12 周后。零假设是，在界面剪切强度和相交表面百分比（定义为微 CT 方案的植入物表面与骨接触的百分比）等主要结果方面，植入物之间没有差异，以及次要结果：刚度、峰值负载、失效能量和微 CT（骨体积/总体积 [BV/TV]、骨小梁厚度 [Tb.Th] 和骨小梁数量 [Tb.N]）和组织形态计量学（骨-植入物接触 [BIC]）参数。
将每种材料（碱性热处理和羟基磷灰石涂层钛）的植入物通过手术插入股骨和胫骨骨干松质骨（每种植入物类型 16 个；干涉配合）和胫骨皮质的三个骨干部位（每种植入物类型 24 个；线对线配合）在 8 只骨骼成熟的绵羊中。术后 12 周，切除骨骼以通过生物力学推通过试验、微 CT 和组织形态计量学评估 AHT 和 PCHA 植入物的骨整合。绵羊的骨成分和重塑模式与人类相似，该模型使我们能够比较植入物与不允许在人类中进行的离体结果。使用线性混合效应模型对主要和次要结果进行了比较，该模型分别为皮质和松质组开发，并包括动物的随机效应、术前体重的协变量以及适当的植入物位置（左/右侧肢体、股骨/胫骨松质、皮质骨干区域和内侧/外侧皮质）。设定显著性水平为 0.05。
调整协变量后，松质骨的界面剪切强度估计边缘均值为 AHT 植入物（9.3 MPa）比 PCHA 植入物（7.7 MPa）高 1.6 MPa（95%CI 0.5 至 2.8；p = 0.006）。同样，调整协变量后，皮质骨的界面剪切强度估计边缘均值为 AHT 植入物（25.5 MPa）比 PCHA 植入物（18.9 MPa）高 6.6 MPa（95%CI 5.0 至 8.1；p < 0.001）。在松质部位未检测到植入物-骨相交表面百分比的差异（松质 AHT 55.1%和 PCHA 58.7%；调整后的估计边缘均值差异 -3.6% [95%CI -8.1%至 0.9%]；p = 0.11）。在皮质骨中，调整协变量后，内侧部位的估计边缘均值相交表面百分比为 AHT 植入物（58.1%）比 PCHA（46.2% [95%CI 7.1%至 16.6%]）高 11.8%（p < 0.001），而外侧部位没有差异（AHT 75.8%和 PCHA 74.9%；调整后的估计边缘均值差异 0.9% [95%CI -3.8%至 5.7%]；p = 0.70）。
这些数据表明，在绵羊模型中，与 PCHA 表面相比，在植入后 12 周时 AHT 表面的骨整合更强。
鉴于 AHT 植入物与皮质和松质骨的界面比 PCHA 植入物更坚固，现在可以使用具有相同几何形状的髋部柄进行非劣效性临床研究，以比较该研究中使用的相同表面。这项临床前研究的结果为进行这样的临床研究提供了伦理基线，因为碱性热处理表面具有降低假体关节感染和增强植入物骨整合的潜力。
