School of Engineering and Physical Sciences, Institute of Mechanical, Process and Energy Engineering, Heriot-Watt University, EH14 4AS, UK.
School of Engineering and Physical Sciences, Institute of Mechanical, Process and Energy Engineering, Heriot-Watt University, EH14 4AS, UK.
J Mech Behav Biomed Mater. 2022 Aug;132:105303. doi: 10.1016/j.jmbbm.2022.105303. Epub 2022 Jun 1.
Bone regeneration in critical-sized defects is a clinical challenge, with biomaterials under constant development aiming at enhancing the natural bone healing process. The delivery of bone morphogenetic proteins (BMPs) in appropriate carriers represents a promising strategy for bone defect treatment but optimisation of the spatial-temporal release is still needed for the regeneration of bone with biological, structural, and mechanical properties comparable to the native tissue. Nonlinear micro finite element (μFE) models can address some of these challenges by providing a tool able to predict the biomechanical strength and microdamage onset in newly formed bone when subjected to physiological or supraphysiological loads. Yet, these models need to be validated against experimental data. In this study, experimental local displacements in newly formed bone induced by osteoinductive biomaterials subjected to in situ X-ray computed tomography compression in the apparent elastic regime and measured using digital volume correlation (DVC) were used to validate μFE models. Displacement predictions from homogeneous linear μFE models were highly correlated to DVC-measured local displacements, while tissue heterogeneity capturing mineralisation differences showed negligible effects. Nonlinear μFE models improved the correlation and showed that tissue microdamage occurs at low apparent strains. Microdamage seemed to occur next to large cavities or in biomaterial-induced thin trabeculae, independent of the mineralisation. While localisation of plastic strain accumulation was similar, the amount of damage accumulated in these locations was slightly higher when including material heterogeneity. These results demonstrate the ability of the nonlinear μFE model to capture local microdamage in newly formed bone tissue and can be exploited to improve the current understanding of healing bone and mechanical competence. This will ultimately aid the development of BMPs delivery systems for bone defect treatment able to regenerate bone with optimal biological, mechanical, and structural properties.
在临界尺寸缺陷中进行骨再生是一项临床挑战，生物材料不断发展，旨在增强自然骨愈合过程。将骨形态发生蛋白（BMPs）递送至适当的载体代表了一种有前途的骨缺损治疗策略，但仍需要优化时空释放，以实现具有与天然组织相当的生物、结构和机械性能的骨再生。非线性微有限元（μFE）模型可以通过提供一种能够预测新形成的骨在生理或超生理负荷下的生物力学强度和微损伤起始的工具来应对其中的一些挑战。然而，这些模型需要经过实验数据的验证。在这项研究中，使用数字体视学（DVC）测量的在位 X 射线计算机断层扫描压缩下诱导的新形成骨中的局部位移，用于验证μFE 模型。均匀线性μFE 模型的位移预测与 DVC 测量的局部位移高度相关，而捕获矿化差异的组织异质性显示出可以忽略的影响。非线性μFE 模型提高了相关性，并表明组织微损伤发生在低表观应变下。微损伤似乎发生在大空腔旁边或生物材料诱导的薄小梁处，与矿化无关。尽管塑性应变积累的局部化相似，但当包括材料异质性时，这些位置积累的损伤量略高。这些结果表明，非线性μFE 模型能够捕捉新形成的骨组织中的局部微损伤，并可用于改善对愈合骨和机械性能的理解。这最终将有助于开发用于骨缺损治疗的 BMP 递送系统，以能够再生具有最佳生物、机械和结构性能的骨。
