Comparative Study on Tissue Differentiation of Bone Marrow Mesenchymal Stem Cells in Irregular Versus Regular Bone Tissue Engineering Scaffolds

doi:10.1007/s12204-025-2819-3

Abstract

Abstract: In bone tissue engineering microstructure design, adjusting the structural design of biomimetic bone scaffolds can provide distinct differentiation stimuli to cells on the scaffold surface. This study explored the biomechanical impacts of different biomimetic microstructures on advanced bone tissue engineering scaffolds. Two irregular bone scaffolds (homogeneous/radial gradient) based on the Voronoi tesselation algorithm and eight regular lattice scaffolds involving pillar body centered cubic, vintiles, diamond, and cube (homogeneous/radial gradient) with constant 80% porosity were constructed. Mechanical stimulation differentiation algorithms, finite element analysis, and computational fluid dynamics were used to investigate the effects of different pore structures on the octahedral shear strain and fluid flow shear stress within the scaffolds, thereby elucidating the differentiation capabilities of the five structural bone/cartilage cell types. The findings demonstrated that irregular structures and radial-gradient designs promoted osteogenic differentiation, whereas regular structures and homogeneous designs facilitated chondrogenic differentiation. The highest percentages of osteoblast and chondrocyte differentiation were observed in radial-gradient irregular scaffolds. This research provides insights into the microstructure design of bone tissue engineering implants.

Key words: Voronoi-tessellation, mechanical stimulation differentiation algorithms, bone cell, cartilage cell

摘要： 在骨组织工程微结构设计中，调整仿生骨支架的结构设计可为支架表面的细胞提供不同的分化刺激。本研究探讨了不同生物仿生微结构对推进骨组织工程支架的生物力学影响。构建了具有恒定 80% 孔隙率的，两种基于泰森多边形算法的不规则骨支架（均质/径向梯度）和八种包括柱状体心立方结构、Vintiles、菱形与立方体的规则晶格支架（均质/径向梯度）。利用机械刺激分化算法、有限元分析和计算流体动力学研究了不同孔隙结构对支架内八面体剪切应变和流体流动剪切应力的影响，阐明了五种结构骨/软骨细胞类型的分化能力。研究结果表明：不规则结构和径向梯度设计可促进成骨细胞分化，而规则结构和均质设计可促进软骨分化；在径向梯度不规则支架中观察到的成骨细胞和软骨细胞分化比例最高。这项研究有助于深入了解骨组织工程植入物的微结构设计。

关键词: 泰森多边形, 机械刺激组织分化算法, 骨细胞, 软骨细胞

CLC Number:

Hai Jizhe, Xu Qingyu, Shan Chunlong, Li Haijie, Jing Lei. Comparative Study on Tissue Differentiation of Bone Marrow Mesenchymal Stem Cells in Irregular Versus Regular Bone Tissue Engineering Scaffolds[J]. J Shanghai Jiaotong Univ Sci, 2025, 30(4): 625-636.

References

[1] SCHEMITSCH E H. Size matters: Defining critical in bone defect size! [J]. Journal of Orthopaedic Trauma, 2017, 31(Sup.5): S20-S22. [2] MARTíNEZ-VáZQUEZ F J, CABA?AS M V, PARIS J L, et al. Fabrication of novel Si-doped hydroxyapatite/gelatine scaffolds by rapid prototyping for drug delivery and bone regeneration [J]. Acta Biomaterialia, 2015, 15: 200-209. [3] ZHANG X B, GONG H, FAN R X, et al. Comparative study between bone tissue engineering scaffolds with bull and rat cancellous microarchitectures on tissue differentiations of bone marrow stromal cells: A numerical investigation [J]. Journal of Bionic Engineering, 2018, 15(5): 924-938. [4] SANDINO C, LACROIX D. A dynamical study of the mechanical stimuli and tissue differentiation within a CaP scaffold based on micro-CT finite element models [J]. Biomechanics and Modeling in Mechanobiology, 2011, 10(4): 565-576. [5] AZIZI P, DROBEK C, BUDDAY S, et al. Simulating the mechanical stimulation of cells on a porous hydrogel scaffold using an FSI model to predict cell differentiation [J]. Frontiers in Bioengineering and Biotechnology, 2023, 11: 1249867. [6] PERIER-METZ C, DUDA G N, CHECA S. Mechano-biological computer model of scaffold-supported bone regeneration: Effect of bone graft and scaffold structure on large bone defect tissue patterning [J]. Frontiers in Bioengineering and Biotechnology, 2020, 8: 585799. [7] PORTER B, ZAUEL R, STOCKMAN H, et al. 3-D computational modeling of media flow through scaffolds in a perfusion bioreactor [J]. Journal of Biomechanics, 2005, 38(3): 543-549. [8] PRENDERGAST P J, HUISKES R, S?BALLE K. Biophysical stimuli on cells during tissue differentiation at implant interfaces [J]. Journal of Biomechanics, 1997, 30(6): 539-548. [9] SUN Y Y, WAN B, WANG R X, et al. Mechanical stimulation on mesenchymal stem cells and surrounding microenvironments in bone regeneration: Regulations and applications [J]. Frontiers in Cell and Developmental Biology, 2022, 10: 808303. [10] WANG G J, SHEN L D, ZHAO J F, et al. Design and compressive behavior of controllable irregular porous scaffolds: Based on voronoi-tessellation and for additive manufacturing [J]. ACS Biomaterials Science & Engineering, 2018, 4(2): 719-727. [11] KOONS G L, DIBA M, MIKOS A G. Materials design for bone-tissue engineering [J]. Nature Reviews Materials, 2020, 5: 584-603. [12] LIU Z Q, GONG H, GAO J Z, et al. Design of new gradient scaffolds based on triply periodic minimal surfaces and study on its mechanical, permeability and tissue differentiation characteristics [J]. Journal of Biomedical Engineering, 2021, 38(5): 960-968 (in Chinese). [13] LIU F, MAO Z F, ZHANG P, et al. Functionally graded porous scaffolds in multiple patterns: New design method, physical and mechanical properties [J]. Materials & Design, 2018, 160: 849-860. [14] LU T, SUN Z W, JIA C W, et al. Roles of irregularity of pore morphology in osteogenesis of Voronoi scaffolds: From the perspectives of MSC adhesion and mechano-regulated osteoblast differentiation [J]. Journal of Biomechanics, 2023, 151: 111542. [15] XU Q Y, HAI J Z, SHAN C L, et al. Mechanical and permeability properties of radial-gradient bone scaffolds developed by voronoi tessellation for bone tissue engineering [J]. Journal of Shanghai Jiao Tong University (Science), 2024. http://dx.doi.org/10.1007/s12204-024-2770-8 [16] HOLLNAGEL D I, SUMMERS P E, POULIKAKOS D, et al. Comparative velocity investigations in cerebral arteries and aneurysms: 3D phase-contrast MR angiography, laser Doppler velocimetry and computational fluid dynamics [J]. NMR in Biomedicine, 2009, 22(8): 795-808. [17] YAP C H, SAIKRISHNAN N, YOGANATHAN A P. Experimental measurement of dynamic fluid shear stress on the ventricular surface of the aortic valve leaflet [J]. Biomechanics and Modeling in Mechanobiology, 2012, 11(1/2): 231-244. [18] MAGROFUOCO E, FLAIBANI M, GIOMO M, et al. Cell culture distribution in a three-dimensional porous scaffold in perfusion bioreactor [J]. Biochemical Engineering Journal, 2019, 146: 10-19. [19] MOKHTARI-JAFARI F, AMOABEDINY G, HAGHIGHIPOUR N, et al. Mathematical modeling of cell growth in a 3D scaffold and validation of static and dynamic cultures [J]. Engineering in Life Sciences, 2016, 16(3): 290-298. [20] SEDDIQI H, SAATCHI A, AMOABEDINY G, et al. Inlet flow rate of perfusion bioreactors affects fluid flow dynamics, but not oxygen concentration in 3D-printed scaffolds for bone tissue engineering: Computational analysis and experimental validation [J]. Computers in Biology and Medicine, 2020, 124: 103826. [21] PAZ C, SUáREZ E, GIL C, et al. Numerical modelling of osteocyte growth on different bone tissue scaffolds [J]. Computer Methods in Biomechanics and Biomedical Engineering, 2022, 25(6): 641-655. [22] MELCHELS F P W, TONNARELLI B, OLIVARES A L, et al. The influence of the scaffold design on the distribution of adhering cells after perfusion cell seeding [J]. Biomaterials, 2011, 32(11): 2878-2884.