Periodic Static Compression of Micro-Strain Pattern Regulates Endochondral Bone Formation

Pengzhen Cheng,Xueyi Zhao, Meige Han,Yaping Zhuang,Fenru Ning,Yaqian Hu,Weiguang Lu,Sheng Miao, Chengxiang Zhao, Liyuan Jia,Xue Hao, Meng Sun, Junxiang Wang,Fulin Chen,Liu Yang,Qiang Jie

FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY（2024）

Northwest Univ | Fourth Mil Med Univ | Shanghai Jiao Tong Univ | Xi An Jiao Tong Univ

Cited 1|Views20

Abstract

Introduction: Developmental engineering based on endochondral ossification has been proposed as a potential strategy for repairing of critical bone defects. Bone development is driven by growth plate-mediated endochondral ossification. Under physiological conditions, growth plate chondrocytes undergo compressive forces characterized by micro-mechanics, but the regulatory effect of micro-mechanical loading on endochondral bone formation has not been investigated.Methods: In this study, a periodic static compression (PSC) model characterized by micro-strain (with 0.5% strain) was designed to clarify the effects of biochemical/mechanical cues on endochondral bone formation. Hydrogel scaffolds loaded with bone marrow mesenchymal stem cells (BMSCs) were incubated in proliferation medium or chondrogenic medium, and PSC was performed continuously for 14 or 28 days. Subsequently, the scaffold pretreated for 28 days was implanted into rat femoral muscle pouches and femoral condylar defect sites. The chondrogenesis and bone defect repair were evaluated 4 or 10 weeks post-operation.Results: The results showed that PSC stimulation for 14 days significantly increased the number of COL II positive cells in proliferation medium. However, the chondrogenic efficiency of BMSCs was significantly improved in chondrogenic medium, with or without PSC application. The induced chondrocytes (ichondrocytes) spontaneously underwent hypertrophy and maturation, but long-term mechanical stimulation (loading for 28 days) significantly inhibited hypertrophy and mineralization in ichondrocytes. In the heterotopic ossification model, no chondrocytes were found and no significant difference in terms of mineral deposition in each group; However, 4 weeks after implantation into the femoral defect site, all scaffolds that were subjected to biochemical/mechanical cues, either solely or synergistically, showed typical chondrocytes and endochondral bone formation. In addition, simultaneous biochemical induction/mechanical loading significantly accelerated the bone regeneration.Discussion: Our findings suggest that microstrain mechanics, biochemical cues, and in vivo microenvironment synergistically regulate the differentiation fate of BMSCs. Meanwhile, this study shows the potential of micro-strain mechanics in the treatment of critical bone defects.

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Key words

periodic static compression,micro-strain,critical bone defects,endochondral bone formation,biomaterials

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The Development, Use, and Challenges of Electromechanical Tissue Stimulation Systems

Jie Hu, William Anderson, Emily Hayes, Ellie Annah Strauss, Jordan Lang, Josh Bacos, Noah Simacek,Helen H. Vu,Owen J. T. Mccarty, Hoyeon Kim,Youngbok (Abraham) Kang

2023

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【要点】：研究揭示了周期性静态压缩（PSC）微应变模式对骨髓间充质干细胞（BMSCs）成软骨和成骨分化的调控作用，为修复关键性骨缺陷提供了新策略。

【方法】：通过设计周期性静态压缩模型，结合微应变（0.5%应变）的生物化学和力学信号，研究对BMSCs在成软骨和成骨分化中的影响。

【实验】：使用载有BMSCs的水凝胶支架，分别在增殖培养基和成软骨培养基中培养，并进行14天或28天的PSC处理。处理后，将预处理28天的支架植入大鼠股肌囊和股骨髁缺陷部位。通过检测发现，14天PSC刺激显著增加增殖培养基中COL II阳性细胞数量；而成软骨培养基中的BMSCs成软骨效率在有无PSC应用下均显著提高。长期机械刺激（28天）显著抑制了诱导软骨细胞（ichondrocytes）的肥大和矿化。异位成骨模型中，各组间矿化沉积无显著差异，但植入股骨缺陷部位4周后，所有经生化/力学信号处理的支架均显示出典型的软骨细胞和软骨内骨形成，同时生化诱导和力学加载的联合应用显著加速了骨再生。

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