Coburn Brandon, Salary Roozbeh Ross
Department of Mechanical and Industrial Engineering, Marshall University, Huntington, WV 25755.
Marshall University.
J Biomech Eng. 2025 Mar 1;147(3). doi: 10.1115/1.4067575.
Cell-laden, scaffold-based tissue engineering methods have been successfully utilized for the treatment of bone fractures and diseases, caused by factors such as trauma, tumors, congenital anomalies, and aging. In such methods, the rate of scaffold biodegradation, transport of nutrients and growth factors, as well as removal of cell metabolic wastes at the site of injury are critical fluid-dynamics factors, affecting cell proliferation and ultimately tissue regeneration. Therefore, there is a critical need to identify the underlying material transport mechanisms and factors associated with cell-seeded, scaffold-based bone tissue engineering. The overarching goal of this study is to contribute to patient-specific, clinical treatment of bone pathology. The overall objective of the work is to establish computational fluid dynamics (CFD) models: (i) to identify the consequential mechanisms behind internal and external material transport through/over porous bone scaffolds designed based on the principles of triply periodic minimal surfaces (TPMS) and (ii) to identify TPMS designs with optimal geometry and flow characteristics for the treatment of bone fractures in clinical practice. In this study, advanced CFD models were established based on ten TPMS scaffold designs for (i) single-unit internal flow analysis, (ii) single-unit external flow analysis, and (iii) cubic, full-scaffold external flow analysis, where the geometry of each design was parametrically created. The influence of several design parameters, such as surface representation iteration, wall thickness, and pore size on geometry accuracy as well as computation time, was investigated in order to obtain computationally efficient and accurate CFD models. The fluid properties (such as density and dynamic viscosity) as well as the boundary conditions (such as no-slip condition, inlet flow velocity, and pressure outlet) of the CFD models were set based on clinical/research values reported in the literature, according to the fundamentals of internal and external Newtonian flow modeling. The main fluid characteristics influential in bone regeneration, including flow velocity, flow pressure, and wall shear stress (WSS), were analyzed to observe material transport internally through and externally over the TPMS scaffold designs. Regarding the single-unit internal flow analysis, it was observed that P.W. Hybrid and Neovius designs had the highest level of not only flow pressure but also WSS. This can be attributed to their relatively flat surfaces when compared to the rest of the TPMS designs. Schwarz primitive (P) appeared to have the lowest level of flow pressure and WSS (desirable for development of bone tissues) due to its relatively open channels allowing for more effortless fluid transport. An analysis of streamline velocity exhibited an increase in velocity togther with a depiction of potential turbulent motion along the curved sections of the TPMS designs. Regarding the single-unit external flow analysis, it was observed that Neovius and Diamond yielded the highest level of flow pressure and WSS, respectively, while Schwarz primitive (P) similarly had a relatively low level of flow pressure and WSS suitable for bone regeneration. Besides, pressure buildup was observed within the inner channels of almost all the TPMS designs due to flow resistance and the intrinsic interaction between the fluid flow and the scaffold walls. Regarding the cubic (full-scaffold) external flow analysis, the Diamond and Schwarz gyroid (G) designs appeared to have a relatively high level of both flow pressure and WSS, while Schwarz primitive (P) similarly yielded a low level of flow pressure and WSS. Overall, the outcomes of this study pave the way for optimal design and fabrication of complex, bone-like tissues with desired material transport properties for cell-laden, scaffold-based treatment of bone fractures.
基于支架的细胞负载组织工程方法已成功用于治疗由创伤、肿瘤、先天性异常和衰老等因素引起的骨折和疾病。在这些方法中,支架的生物降解速率、营养物质和生长因子的运输,以及损伤部位细胞代谢废物的清除是关键的流体动力学因素,影响细胞增殖并最终影响组织再生。因此,迫切需要确定与基于支架的骨组织工程细胞接种相关的潜在物质运输机制和因素。本研究的总体目标是为特定患者的骨病理学临床治疗做出贡献。这项工作的总体目标是建立计算流体动力学(CFD)模型:(i)确定基于三重周期最小表面(TPMS)原理设计的多孔骨支架内部和外部物质运输背后的相关机制,以及(ii)确定在临床实践中治疗骨折具有最佳几何形状和流动特性的TPMS设计。在本研究中,基于十种TPMS支架设计建立了先进的CFD模型,用于(i)单单元内部流动分析、(ii)单单元外部流动分析和(iii)立方体全支架外部流动分析,其中每个设计的几何形状是通过参数创建的。研究了几个设计参数,如表面表示迭代、壁厚和孔径对几何精度以及计算时间的影响,以获得计算效率高且准确的CFD模型。根据内部和外部牛顿流动建模的基本原理,基于文献报道的临床/研究值设置CFD模型的流体属性(如密度和动态粘度)以及边界条件(如无滑移条件、入口流速和压力出口)。分析了对骨再生有影响的主要流体特性,包括流速、流动压力和壁面剪应力(WSS),以观察物质在TPMS支架设计内部和外部的运输情况。关于单单元内部流动分析,观察到P.W. Hybrid和Neovius设计不仅具有最高水平的流动压力,还具有最高水平的WSS。这可以归因于与其他TPMS设计相比,它们的表面相对平坦。Schwarz primitive(P)由于其相对开放的通道允许更轻松的流体运输,似乎具有最低水平的流动压力和WSS(有利于骨组织发育)。流线速度分析显示,沿着TPMS设计的弯曲部分流速增加,同时描绘了潜在的湍流运动。关于单单元外部流动分析,观察到Neovius和Diamond分别产生最高水平的流动压力和WSS,而Schwarz primitive(P)同样具有适合骨再生的相对较低水平的流动压力和WSS。此外,由于流动阻力以及流体流动与支架壁之间的内在相互作用,几乎所有TPMS设计的内部通道内都观察到压力积聚。关于立方体(全支架)外部流动分析,Diamond和Schwarz gyroid(G)设计似乎具有相对较高水平的流动压力和WSS,而Schwarz primitive(P)同样产生较低水平 的流动压力和WSS。总体而言,本研究的结果为具有所需物质运输特性的复杂骨样组织的优化设计和制造铺平了道路,用于基于支架的细胞负载治疗骨折。